IMS Company Profiles - Report Buyer

IMS Company Profiles 

Takeda - March 2009

IMS COM PANY PRO FILES TAKEDA 

Ed i to rial Team 

Nora Mc Car thy - Ex ec u tive Ed i tor 

Selena Class - Dep uty Ex ec u tive Ed i tor 

Su san Murray - Se nior Ed i tor 

Catherine Don nel ly - Ed i tor 

Angie Fra ser - Editor 

Mar ket ing 

Rich ard Derrick 

De sign & Type set ting 

Sophie Avery 

IMS HEALTH 

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Lon don 

NW1 6JB, UK 

Tel: +44 (0)20 3075 5888, Fax: +44 (0)20 3075 5346 

Visit our web site at http://www.imshealth.com 

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© 2009 IMS Health In cor po rated or its af fil i ates Page 2


IMS Com pany Pro files 

The IMS Com pany Pro files ser vice com prises in di vid ual in-depth re ports cov er ing all as pects of phar ma - 

ceu ti cal cor po ra tions and com pa nies. To gether they build up to pro vide a com pre hen sive ref er ence 

source on the play ers in the in ter na tional healthcare sec tor, whether ac tive in many mar kets, or niche 

play ers; pub lic or pri vate; op er at ing lo cally or world wide. 

Each Pro file aims to give de tailed cov er age of the com pany’s struc ture, strat egy, fi nan cial re sults, re - 

search and de vel op ment pro gram, prod uct port fo lio, and ma jor events. In for ma tion is sourced from in - 

ter views with key ex ec u tives of the com pany, stock bro ker fore casts and com men tary, and pub lished 

in for ma tion. In de pend ent, com pa ra ble sales data on the com pany is in cluded, de rived from IMS 

HEALTH’s da ta base of au dited in ter na tional sales data, MI DAS. 

The ser vice is avail able in a va ri ety of for mats, in clud ing PDF files via e-mail, CD-ROM, on-line (Datastar, 

Di a log and STN) and on the Web. 

For fur ther in for ma tion about the IMS Com pany Pro files ser vice, in clud ing the in for ma tion con tained in 

this Pro file, please call IMS HEALTH on +44 (0)20 3075 5888. 



Ta ble of Con tents 

Cor po rate Struc ture . . . . . . . . . . . . . . . . . . 5 

Strat egy State ment . . . . . . . . . . . . . . . . . . 7 

Fi nan cial Re view . . . . . . . . . . . . . . . . . . . 16 

Lat est Re sults . . . . . . . . . . . . . . . . . . 17 

An a lyst Com ment . . . . . . . . . . . . . . . . 17 

Prod uct Port fo lio . . . . . . . . . . . . . . . . . . . 19 

R&D Pro file . . . . . . . . . . . . . . . . . . . . . 54 

Fi nan cial Data . . . . . . . . . . . . . . . . . . . . 78 

Key Fig ures . . . . . . . . . . . . . . . . . . . 78 

An a lyst Fig ures . . . . . . . . . . . . . . . . . 80 

IMS Sales Data . . . . . . . . . . . . . . . . . 83 

Em ployee Data . . . . . . . . . . . . . . . . . . . 88 

Li cens ing/Co-Mar ket ing Agree ments . . . . . . . . . . 89 

Ma jor Events . . . . . . . . . . . . . . . . . . . . 106 

Ap pen dix - Cur rent Com pany Pro files . . . . . . . . . 122 



Corporate Structure 

Head Of fice: Takeda Phar ma ceu ti cal Com pany Lim ited 

1-1, Doshomachi 4-chome 

Chuo-ku 

Osaka 540-8645 

Ja pan 

Tel: +81 (6) 6204 2111 

Fax: +81 (6) 6204 2880 

Home Page: www.takeda.com 

Chair man: Kunio Takeda 

Pres i dent: Yasuchika Hasegawa 

Se nior Man ag ing Di rec tor: Makoto Yamaoka 

Man ag ing Di rec tors: Hiroshi Shinha 

Yasuhiko Yamanaka 

Shigenori Ohkawa 

Cor po rate Au di tor: Toyoji Yoshida 

Naohisa Takeda 

Tadashi Ishikawa 

Tsuguoki Fujinuma 

Cor po rate Of fi cers: Hiroshi Takahara 

Kanji Negi 

Hiroshi Sakiyama 

Teruo Sakurada 

Hiroshi Ohtsuki 

Source: Takeda An nual Re ports 



Takeda was the world’s num ber 16 phar ma ceu ti cal cor po rate group and Ja pan’s lead ing phar ma ceu ti - 

cal cor po ra tion in the year end ing Sep tem ber 2008, ac cord ing to IMS. Un til re cent years, Takeda was 

by far the larg est Jap a nese pharmaceuticals com pany, but a wave of con sol i da tion ac tiv ity in the Jap a - 

nese in dus try has pro duced com pa nies with a bulk that has at points chal lenged Takeda’s dom i nance. 

Takeda has for many years been heavily re li ant on sales from four global stra te gic prod ucts: Actos 

(pioglitazone) for type 2 di a be tes; the antiulcerant Takepron/Prevacid (lansoprazole); Blopress 

(candesartan) for hy per ten sion and Lupron/Leuplin (leuprorelin) for pros tate can cer. The main chal lenge 

for Takeda has been pro duc ing strong pipe line can di dates that will plug the gap as all four prod ucts lose 

pat ent pro tec tion over the next five years, some thing that Takeda has ad dressed pri mar ily through li - 

cens ing deals and ac qui si tions. In May 2008, Takeda com pleted the larg est ever ac qui si tion by a Jap a - 

nese com pany, of US on col ogy com pany Mil len nium Pharma in a Yen1 tril lion deal, boost ing its on col ogy 

pipe line and over seas pres ence. Takeda has made a num ber of ac qui si tions over re cent years to boost its 

pipe line, in clud ing that of Paridigm Ther a peu tics, Syrrx and Amgen Ja pan which in cluded the in au gu ra - 

tion of most of Amgen Ja pan’s (mainly on col ogy) pipe line. Takeda has a strong over seas pres ence and 

has had a long-stand ing and very suc cess ful joint ven ture (TAP Pharmaceuticals) in the US mar ket with 

Abbott, but the loss of ex clu siv ity for TAP’s main prod uct, Takepron/Prevacid re sulted in a de clin ing con - 

tri bu tion from TAP. Af ter 30 years to gether, Takeda de cided to dis solve the jv from mid-2008 and has 

bought Abbott’s share, gain ing full rights to Takepron in re turn for Lupron. Takeda’s fol low-on prod ucts 

for Takepron and Actos, Kapidex (TAK 390MR) and alogliptin (SYR 322), have suf fered ag o niz ing de lays 

in FDA re view for ap proval dates but are near ing the mar ket and Takeda hopes that their launch along 

with growing sales of Millennium’s anticancer drug Velcade (bortezomib) to start bridging the gap as the 

patents losses are realized. 

Share Data: Shares are quoted on the Lon don, Osaka, To kyo, Nagoya, Fukuoka, Hi ro shima, Sapporo 

and Niigata Stock Ex changes. 

Takeda has the fol low ing busi ness seg ments: 

� Pharmaceuticals (in clud ing ethicals and con sumer healthcare) 

��Other Prod ucts (in clud ing food, chem i cals, an i mal health) 



In tro duc tion 

• Larg est ever Jap a nese ac qui si tion 

Strategy Statement 

Takeda was the world’s num ber 16 phar ma ceu ti cal cor po rate group and re gained its po si tion as Ja pan’s 

lead ing phar ma ceu ti cal cor po ra tion ac cord ing to IMS in the year end ing Sep tem ber 2008. Takeda was, 

un til re cently, by far the larg est Jap a nese phar ma ceu ti cal com pany but its pre dom i nance was chal lenged 

by a wave of con sol i da tion in the Jap a nese in dus try over the past few years push ing it briefly down to sec - 

ond place be hind Daiichi Sankyo. The flurry of merger ac tiv ity in the Jap a nese mar ket, which also cre ated 

Astellas (Fujisawa and Yamanouchi), Dainippon Sumitomo and Mitsubishi Tanabe Pharma, was driven by 

in fil tra tion from for eign firms with healthy pipe lines and mas sive R&D bud gets; Pfizer sat be hind Daiichi 

Sankyo as the third lead ing pharmaceutical corporation in Japan in the same period. 

Takeda has for many years been re li ant on sales from four lu cra tive global prod ucts: Actos (pioglitazone) 

for type 2 di a be tes; the antiulcerant Takepron/Prevacid (lansoprazole); Blopress (candesartan) for hy - 

per ten sion and Lupron/Leuplin (leuprorelin) for pros tate can cer. Takeda has faced its main chal lenge to 

build strong pipe line can di dates to plug the gap of loom ing pat ent ex pi ra tions of all four foun da tion prod - 

ucts over the next five years, some thing that Takeda has been ad dress ing through li cens ing deals and 

stra te gic ac qui si tions of prod ucts, tech nol ogy and even com pa nies. Takeda’s big gest ac qui si tion to date, 

and the larg est ever ac qui si tion by a Jap a nese Pharma com pany took place in May 2008, of Mil len nium 

Pharma, in a Yen1 tril lion deal. As well as ex pand ing its over seas pres ence, Mil len nium pro vides a huge 

boost to Takeda’s on col ogy pipe line with a num ber of prom is ing can di dates and its main stay mar keted 

prod uct Velcade (bortezomib), an anticancer proteasome in hib i tor, mar keted world wide and in Ja pan by 

John son & John son. Also in 2008, Takeda took a 100% stake in Amgen’s Jap a nese sub sid iary via a share 

trans fer, while gain ing li cens ing rights to 13 clin i cal (mostly on col ogy) can di dates. This fol lowed a num ber 

of stra te gic ac qui si tions over re cent years to boost its pipe line, in clud ing that of Par a digm Ther a peu tics in 

2007 and Syrrx in 2005, the lat ter bringing the dipeptidyl peptidase IV (DPP-IV) inhibitor alogliptin (SYR 

322), currently awaiting US approval. 

With growth hard to find at home, Takeda has had to look to over seas mar kets and has long dis tin guished 

it self from other Jap a nese com pa nies in its for ward-think ing over seas ex pan sion pol i cies and will ing ness 

to do busi ness with for eign phar ma ceu ti cal com pa nies. Takeda has had a long-stand ing and very suc - 

cess ful joint ven ture (TAP Pharmaceuticals) in the USA with Abbott (USA), but the loss of ex clu siv ity for 

TAP’s main prod uct, Prevacid (lansoprazole) has re sulted in a de clin ing con tri bu tion from TAP. Af ter 30 

years to gether, Takeda de cided to dis solve the jv from mid-2008 and paid $1.5 bil lion for Abbott’s share 

of the jv, gain ing full rights to Takepron. The 50% share in TAP will be fully in te grated into Takeda’s grow - 

ing stand-alone op er a tion, Takeda Pharmaceuticals North Amer ica (TPNA), through which it is cur rently 

pro mot ing Rozerem for in som nia and Actos and in the first half of 2009 will add two new prod ucts: 

Kapidex (dexlansoprazole/TAK 390MR), a pro ton pump in hib i tor ap proved in Jan u ary 2009 and Uloric 

(fexobustat/TMX 67) for the treat ment of hyperuricemia in pa tients with gout, ap proved in Feb ru ary 

2009. Al though Ab bot ob tained rights to Lupron, and re lated as sets as well as all em ploy ees, the move 

will, according to Takeda, make it a top 15 US company. 



Back ground 

• Sharp en ing focus on prescription pharmaceuticals 

Founded in 1781 by Chobei Takeda I, Takeda started out as a small busi ness sell ing Jap a nese and Chi - 

nese tra di tional med i cines in Doshomachi, Osaka. In 1871, Chobei Takeda IV was one of the first in Ja pan 

to im port for eign med i cines, by form ing a co op er a tive un ion in Yo ko hama to pur chase drugs from for eign 

trad ing com pa nies. To day, Takeda dom i nates the Jap a nese phar ma ceu ti cal in dus try and is amongst the 

top 20 phar ma ceu ti cal groups in the world. In re cent years Takeda has sold off non-core busi nesses to 

con cen trate on its pharmaceuticals in ter ests, which include OTC products as well as ethicals. 

These di ves ti tures have in cluded the sale of its re main ing 34% share in the BASF Takeda Vi ta min joint 

ven ture to BASF Ja pan, com plet ing its exit from the do mes tic bulk vi ta min busi ness. Takeda has also dis - 

posed of its Syn thetic Rub ber La tex busi ness, trans ferred its Food and Vi ta mins ac tiv i ties to a joint ven - 

ture with Kirin (Ja pan), which ac quired all of the jv in 2007, and trans ferred its do mes tic agro chemi cal 

busi ness to a joint ven ture, Sumitomo Chem i cal Takeda Agro Com pany. It has also di vested to 

Schering-Plough (USA) its 40% stake in the two com pa nies’ Jap a nese an i mal health jv, Takeda 

Schering-Plough An i mal Health, which be came a wholly-owned sub sid iary of S-P, drop ping Takeda from 

its name. In 2005, Takeda sold five small sub sid iary com pa nies to Osaka Gas Chem i cals, in clud ing Ja pan 

EnviroChemicals, which had been spun off two years be fore into an independent subsidiary as a prelude 

to full divestment. 

In 2006, Takeda sharp ened its fo cus on pre scrip tion drugs fur ther by ex it ing the Mitsui Takeda Chem i cals 

Inc. joint ven ture (MTCI), by trans fer ring its share of the busi ness to Mitsui Chem i cals, Inc. (Ja pan). MTCI 

was es tab lished as a joint ven ture be tween MCI (51%) and Takeda (49%) in 2001, and it was stip u lated 

in the orig i nal agree ment that the trans fer of shares held by Takeda would take place af ter five years from 

the start of MTCI’s commercial operation. 

Also in 2006, Takeda started the pro cess of di ves ti ture of its do mes tic food and bev er age busi ness to a 

joint ven ture set up with the Jap a nese firm House Foods Cor po ra tion. The House Wellness Foods Cor po - 

ra tion was es tab lished, 66%-owned by House Foods and 34%-owned by Takeda. The pro cess will in volve 

the trans fer of most (298) Takeda Food em ploy ees for 18 months be fore the jv is dis solved and House ac - 

quires Takeda’s hold ing and con verts the jv to a wholly owned subsidiary. 

Takeda has suc ceeded in ex pand ing over seas by set ting up for eign sub sid iar ies and joint ven tures, no ta - 

bly that with Abbott (USA) in North Amer ica (TAP). TAP, dis solved in mid-2008, had launched a num ber 

of lu cra tive, block buster drugs, in clud ing the antiulcerant Prevacid (lansoprazole), antihypertensive 

Blopress (candesartan cilexetil), the oral antidiabetic Actos (pioglitazone), and the hor monal prod uct 

Lupron/Leuplin (leuprorelin). 

M&A Ac tiv ity 

• On col ogy growth in Ja pans bggest acquisition 

Takeda aims to be come one of the top three on col ogy com pa nies and 2008 was a year of on col ogy deals 

for Takeda with sub stan tial agree ments with Amgen, Cell Genesys, Mil len nium and Alnylam, boost ing its 

ca pa bil i ties in this area. In May 2008, Takeda com pleted its Yen1 tril lion ($8.8 bil lion) ac qui si tion of Mil - 

len nium Pharmaceuticals, with Mil len nium be com ing a wholly-owned sub sid iary of Takeda but con tin u ing 

op er a tions as a stand alone busi ness in the US. Pres i dent Dr Deborah Dunsire will con tinue to lead the 

com pany and Takeda has ex pressed its in tent to re tain Mil len nium em ploy ees (around 1,000 em ploy - 

ees). This is the larg est ac qui si tion ever made by Takeda and more over, any Jap a nese phar ma ceu ti cal 

com pany, dem on strat ing Takeda’s com mit ment to be come a true global phar ma ceu ti cal com pany with 



grow ing strength in on col ogy, in which Mil len nium has a strong pres ence. With sales of $0.5 bil lion in 

2007 and net prof its of $15 mil lion, an a lysts con sid ered the bid price for Mil len nium as sur pris ingly high, 

but enough to ward off com pe ti tion from other po ten tial coun ter bid ders such as John son & John son, 

spec u lated to be a nat u ral con tended due to its co-pro mo tion of anticancer drug Velcade (bortezomib), 

Mil len nium’s main stay prod uct. Mil len nium also brings a pipe line con sist ing mainly of on col ogy and in - 

flam ma tory drugs. On col ogy ad di tions from Mil len nium in clude: MLN 0518 for glioblastoma and acute 

myelocytic leu ke mia and MLN 8237/8054 for ad vanced ma lig nan cies in ad di tion to ex panded in di ca tions 

for its main stay prod uct Velcade. Mil len nium has two prod ucts in clin i cal de vel op ment for in flam ma tory 

bowel dis ease: MLN 002 for ul cer ative co li tis and Crohn’s dis ease and an oral drug for Crohn’s disease, 

MLN 3126. Others in development for inflammation include MLN 3897/3701 for inflammatory disease 

and MLN 1202 for atherosclerosis. 

Takeda’s ac tive ac qui si tion year also saw the con clu sion of Takeda and Abbott’s jv in the US, TAP in May 

2008, with Takeda mak ing a $1.5 bil lion pur chase of Abbott’s 50% share, which merged with Takeda to 

be come a wholly owned sub sid iary of Takeda Amer ica Hold ings, Inc. This came hot on the heels of 

Takeda’s April 2008 launch of its wholly-owned sub sid iary Takeda Bio De vel op ment Cen ter Lim ited 

(Takeda Bio) in Ja pan, which it ac quired from Amgen K.K in ac cor dance with a share trans fer agree ment 

be tween Takeda and Amgen in Feb ru ary 2008. Masaomi Miyamoto will chair the board and Hiroyasu 

Hakamura will be pres i dent of Takeda Bio which has around 140 em ploy ees with un dis closed cap i tal. The 

full cost of the Amgen Ja pan ac qui si tion has not been dis closed but re flects Takeda’s plans to re in force its 

pipe line while Amgen can ac cel er ate the development of its products in Japan. 

Takeda’s move to buy into the lu cra tive on col ogy set ting re flects other sim i lar strat e gies, in clud ing Eli 

Lilly’s $6.5 bil lion pur chase of ImClone Sys tems to ob tain Erbitux (cetuximab) and a pipe line of 

early-stage on col ogy prod ucts. The strength of the Yen ver sus the dol lar has also made US com pa nies 

par tic u larly at trac tive tar gets and the ac qui si tion of Mil len nium came in the midst of a Jap a nese spend ing 

spree of for eign firms. This started with Eisai’s $3.9 bil lion take over of MGI Pharma in the USA in De cem - 

ber 2007 through to Shionogi’s Oc to ber 2008 $1.4 bil lion merger with Sciele. Daiichi Sankyo made a $4.6 

bil lion pur chase of In dia’s Ranbaxy in June 2008 af ter al ready in vest ing in a Ger man com pany (U3) while 

Eisai’s pur chase closely fol lowed two pre vi ous US in vest ments of Morphotek and Ligand, that ex panded 

its on col ogy fran chise. Ja pan’s other ma jor player Astellas purchased Agensys for $0.5 billion in 2007. 

Takeda has also been ac tively ac quir ing com pa nies in re cent years when 2007 saw the pur chase of Par a - 

digm Ther a peu tics (Sin ga pore) build ing on a CNS al li ance started in 2005. Par a digm fo cuses on iden ti fy - 

ing small mol e cule tar gets within key gene fam i lies and its pipe line in cludes tar gets and late stage 

pre clin i cal pro jects in pain, CNS, hor mone de pend ent dis eases such as pros tate and breast can cer as well 

as met a bolic dis ease. Fi nan cial terms were not dis closed. Par a digm will be come a sub sid iary of Takeda 

Eu rope Hold ings B.V. a wholly owned sub sid iary of Takeda and Par a digm will be re named Takeda Cam - 

bridge Lim ited with the sub sid iary in Sin ga pore re named Takeda Sin ga pore Pte Lim ited.. 2007 also saw 

the com ple tion of Wyeth’s buyout of Takeda’s in ter est in Wyeth KK (Jap a nese unit of Wyeth) af ter four 

years. The com pa nies re ported that this will have no ef fect on their re la tion ship which re mains strong 

with their cur rent co-pro mo tion of Enbrel. In 2005 Takeda made a stra te gic ac qui si tion of pri vate US 

biotech com pany Syrrx in a $270 mil lion bid to en hance its R&D op er a tions in the US and pipe line, bring - 

ing Takeda one of its most prom is ing new growth prod ucts alogliptin (SYR 322), await ing ap proval in the 

US (see R&D). Set up in 1999, San Diego-based Syrrx, which at the time em ployed around 90 people, 

was to become a subsidiary of the wholly owned US holding entity, Takeda America Holdings. 

The line of ac qui si tions over the past few years has fit ted with Takeda pres i dent’s com ments in 2006 that 

al though Takeda would n’t ac quire just to gain bulk, it would con sider ac quir ing com pa nies in any area 

where it was clearly de fi cient, and the ac qui si tion “would be quicker than do ing it on our own to catch up” 

add ing that Takeda was ac tively seek ing to ac quire com pa nies with ca pa bil i ties to “de velop in ves ti ga - 

tional new drugs in our priority fields.” 



Re gional Strat egy 

• Takeda hopes to be in the US top 15 

Takeda is a Jap a nese leader in es tab lish ing it self over seas and gen er ates a much higher pro por tion of its 

sales in the US mar ket than most Jap a nese com pa nies. This is how ever be ing threat ened with forth com - 

ing pat ent ex pi ra tions of lead ing prod ucts, and in fis cal 2007 (end ing March 2008) Takeda’s share of 

com pany sales gen er ated in the US dropped from nearly one-third to one-quar ter. Takeda now claims it 

will be one of 15 lead ing com pa nies in the US how ever, fol low ing the pur chase of Abbott’s share of TAP, 

which has now merged with Takeda to be come a wholly owned sub sid iary of Takeda Amer ica Hold ings, 

Inc, 100%-owned by Takeda. Takeda ex pects syn er gis tic ef fects of about Yen40 bil lion over the 

three-year pe riod fol low ing the merger, which com pleted in te gra tion and started busi ness as a new con - 

sol i dated com pany in July 2008. As sets were split equally. Abbott ob tained rights to Lupron De pot along 

with as sets pri mar ily re lated to this prod uct, and all em ploy ees as well as pay ments based on TAP’s other 

cur rent and cer tain fu ture prod ucts. The new TAP sub sid iary of TAH will re tain the other mar keted TAP 

prod uct, Prevacid (al though Abbott will re ceive around $1.5 bil lion from prod uct sales over five years). 

Around 2,600 of the 3,000 em ploy ees of TAP (in clud ing 1,400 MRs) were trans ferred to the Takeda 

group; the num ber of MRs of the new Takeda group has in creased to about 3,500. TAP de vel op ment 

func tions have been trans ferred to Takeda Global Re search and De vel op ment Cen tre (TGRD) by trans - 

fer ring TAP pipe line prod ucts: Kapidex (dexlansoprazole/TAK 390MR), a pro ton pump in hib i tor ap proved 

in Jan u ary 2009; an other pro ton pump inhibior, ilaprazole (IY 81149) and Uloric (febuxostat/TMX 67) for 

the treat ment of hyperuricemia in pa tients with gout, ap proved in Feb ru ary 2009. Takeda Phar ma ceu ti - 

cal North Amer ica (TPNA) will now have two new prod uct launches dur ing the first half of 2009. TPNA has 

grown from hav ing 6 em ploy ees in 1998, when it was in cor po rated, to 3,000 in 2006. In many ways, 

given the im por tance of the US market and the lack of growth opportunities elsewhere, the success of 

TPNA could be seen as a symbol for the success of Takeda itself. 

Takeda is cur rently pres ent in Ja pan, the US, six Eu ro pean coun tries and five Asian coun tries and in its 

last man age ment plan, it set it self the goal of main tain ing its lead ing po si tion in Ja pan, with a mar ket 

share of 7%. In the all-im por tant US mar ket, the com pany wants TPNA to achieve a mar ket share of 

more than 1.5%, and in Eu rope it ex pects more than 1.1% mar ket share in the six larg est coun tries. In 

the five main coun tries in Asia, Takeda has set a tar get of more than 1.4% mar ket share. The tar get over - 

all mar ket share is 2.5% in the coun tries where Takeda has its own sales chan nels. Takeda has how ever 

re cently ad mit ted to strug gling in its at tempts to strengthen its pres ence in Eu rope and fully entering 

emerging markets. 

Ther a peu tic Fo cus 

• On col ogy ac qui si tion may bridge loom ing gap 

Takeda is well po si tioned with re gard to ther a peu tic fo cus; for many years, a large pro por tion of sales 

have been gen er ated from the high growth di a be tes and on col ogy ar eas, as well as anti-ulcerants; oral 

antidiabetics; an gio ten sin II an tag o nists; and cephalosporin an ti bi ot ics. Its ma jor prod ucts are 

Prevacid/Takepron (lansoprazole), a pro ton pump in hib i tor; Actos (pioglitazone), an oral agent for di a be - 

tes; the can cer and hor monal prod uct Leuplin/Lupron (al though this is now ex clu sively owned by Abbott 

fol low ing the dis so lu tion of the TAP jv); and the an gio ten sin II in hib i tor Blopress/Atacand (candesartan 

cilexetil) for hy per ten sion. Takeda faces a huge chal lenge as all four prod ucts lose pat ent pro tec tion over 

the next five years with Prevacid in No vem ber 2009 fol lowed by Actos in 2011 then Blopress in 2012 and 

finally Leuplin in 2014. 

Blopress was the best sell ing phar ma ceu ti cal prod uct in Ja pan in the year end ing Sep tem ber 2008 ac - 

cord ing to IMS. Takeda is de vel op ing a fixed-dose com bi na tion of candesartan with the cal cium an tag o - 



nist amlodipine in Ja pan, which will com bine two of Ja pan’s best sell ing drugs; in Ja pan doc tors of ten 

co-pre scribe an ARB and cal cium an tag o nist to achieve blood pres sure tar gets with sin gle treat ment said 

to achieve this in only half of pa tients. If ap proved this will com pete with other com pa nies de vel op ing 

such com bi na tions in Ja pan: Daiichi Sankyo with Azor (olmesartan + amlodipine), ex pected to be filed for 

ap proval in 2009 and Novartis with Exforge (valsartan + amlodipine), both mar keted in the US. Takeda 

and AstraZeneca’s com bi na tion of candesartan cilexetil and hy dro chlo ro thi a zide (Blopress Comp) is 

avail able in most mar kets world wide for the treat ment of hy per ten sion and ap proval as Ecard was 

granted in Ja pan in Jan u ary 2009. Blopress had also been in de vel op ment for di a betic retinopathy but fol - 

low ing non-sta tis ti cally sig nif i cant re sults from the four year DI RECT pro gram in volv ing over 5,000 pa - 

tients, Takeda de cided not to pur sue this in di ca tion; candesartan re duced the in ci dence of di a betic 

retinopathy by 18% compared with placebo however and results were published in The Lancet. 

The ac qui si tion of Mil len nium brought Takeda its main stay prod uct Velcade (bortezomib), an anticancer 

proteasome in hib i tor, mar keted world wide and in Ja pan by John son & John son. Al though an a lysts crit i - 

cized the deal for be ing too ex pen sive, six months on, it looks to have been a well-planned move as 2008 

sales of Velcade topped $1 bil lion, boosted by the June 2008 ap proval as a first-line ther apy for mul ti ple 

myeloma. It was al ready used as sec ond and third line ther apy in mul ti ple myeloma and ad di tional clin i cal 

re sults re leased at the Amer i can So ci ety for He ma tol ogy meet ing sug gest the drug will re main an im por - 

tant cor ner stone of myeloma treat ment for years to come. Takeda hopes that this prod uct may help to 

bridge the loom ing gap from up com ing pat ent ex pi ries of its main stay prod ucts where the pat ent ex pi ra - 

tion of Actos and Prevacid alone is ex pected to amount to annual losses of over Yen500 billion in 2009 

through 2011. 

R&D 

• Ag o niz ing de lays for alogliptin... 

Takeda is one of the six Jap a nese com pa nies with an an nual R&D bud get of around $1 bil lion, the spend - 

ing of which is crit i cally im por tant in or der to pri or i tize in vest ment in their pipe line. R&D at Takeda is fo - 

cused around four ar eas: on col ogy and urol ogy; life style dis eases, cen tral ner vous sys tem (CNS) and 

gas tro in tes ti nal (GI) dis or ders. The ac qui si tion of Mil len nium, giv ing ac cess to mar keted prod uct Velcade 

and 10 early stage mol e cules has been de scribed as the most sig nif i cant and stra te gi cally transformative 

deal in Takeda’s his tory, giv ing a large boost to its on col ogy fran chise. The ad di tion of Velcade may be 

Takeda’s lone bright spot as the pat ent ex pi ra tions of main stay prod ucts Actos and Prevacid near with lit - 

tle other than Velcade to sig nif i cantly fill the gap fol low ing un for tu nate de lays from missed PDUFU dates 

for both fol low-on prod ucts, Kapidex (TAK 390MR), a mod i fied re lease ver sion of an ac tive en an tio mer of 

Prevacid (lansoprazole) for acid re lated dis eases and the dipeptidyl peptidase IV (DPP-IV) in hib i tor 

alogliptin. Ex pected to be come Takeda’s two new main stay prod ucts, Kapidex was fi nally ap proved in 

Jan u ary 2009, mean ing it will be launched be fore the loss of pat ent pro tec tion for Prevacid in No vem ber. 

Ap proval of alogliptin is de layed un til June 2009 how ever, a de lay of eight months from the orig i nal date 

and it now lags well be hind Merck &Co’s Januvia (sitagliptin), which has be come the ‘gold stan dard’ for 

the DPP-IV in hib i tor class, with new prod ucts ex pected to show su pe ri or ity. An a lysts so far seem to be of 

the opin ion that alogliptin only of fers sim i lar safety and ef fi cacy to Januvia, al though the ex act in di ca tion 

Takeda seeks is not fully re vealed. Takeda does how ever have greater experience in diabetes, and that 

approval of a pill combining alogliptin with Actos is also expected in the second half of 2009. 

The ac qui si tion of Mil len nium also brought ex pan sion in the field of in flam ma tion with vedolizumab (MLN 

002), a hu man ized monoclonal an ti body that spe cif i cally binds with cell ad he sion mol e cule for in flam ma - 

tory bowel dis ease which Takeda in tends to file for ap proval in Ja pan, the US and Eu rope in 2011. Two 

phase III tri als were ini ti ated in Jan u ary 2009, as part of the GEM INI pro gram that will study vedolizumab 

in ul cer ative co li tis and Crohn’s dis ease, en roll ing 2,000 pa tients from 40 coun tries (in clu sion of Ja pan not 

yet de cided) with mod er ate-to-se vere dis ease, un re spon sive to stan dard ther a pies. Takeda hopes this 



will fur ther en hance its pres ence in the mar ket for gas tro in tes ti nal drugs which it has established with the 

PPI lansoprazole. 

The ac qui si tion of Amgen in Ja pan is a strong mes sage that Takeda will fully em bark on ad vanced phar - 

ma ceu ti cal de vel op ment in the fields of on col ogy and an ti body pharmaceuticals. Takeda Bio pres i dent re - 

vealed am bi tions to com mence clin i cal de vel op ment of the 10 pre clin i cal can di dates by 2010 and to file 

for ap proval of prod ucts gained from the in au gu ra tion of Amgen Ja pan. This started with Vectibix 

(panitumumab), a co lon can cer hu man monoclonal an ti body to the ep i the lial growth fac tor re cep tor 

(EGFR), which was filed for ap proval in June 2008 for colorectal can cer. A fil ing for motesanib, an 

antiangiogenic small mol e cule in phase III tri als in the USA, Eu rope and Ja pan in 2009, is planned by 

2010. Pa tient en rol ment in the MONET1 trial of motesanib in the treat ment of nonsmall cell lung can cer 

(NSCLC) was tem po rarily sus pended in No vem ber 2008 how ever, based on a higher early mor tal ity rate 

with motesanib. The trial’s in de pend ent Data Mon i tor ing Com mit tee (DMC) rec om mended im me di ate 

dis con tinu a tion of motesanib ther apy in pa tients with squamous NSCLC be cause of a higher than ex - 

pected hemoptysis rate in these pa tients but not in pa tients with non-squamous NSCLC and in Feb ru ary 

2009, the DMC recommended the resumption of enrollment of patients with non-squamous NCSLC. 

Li cens ing 

• ‘Deal of the year’ pi o neers RNAI in Ja pan 

Takeda says its ag gres sive al li ance pol icy aims at a wide range of tech nol o gies and prod ucts and the com - 

pany has said it will ac quire any new tech nol ogy and prod uct nec es sary for the com pany to com pete on 

the global mar ket with top man age ment in volved in all deals of any size. 2008 was a par tic u larly ac tive 

year as the com pany worked to tackle its long-stand ing chal lenges, in clud ing es tab lish ing and strength - 

en ing its pres ence in the global mar ket, en hanc ing its pres ence in on col ogy in ad di tion to sugar me tab o - 

lism and car dio vas cu lar med i cine, as well as in creas ing pro duc tiv ity of R&D. In May 2008, Takeda en tered 

a $1 bil lion li cens ing deal with Alynlam gain ing ac cess to its RNA in ter fer ence tech nol ogy in on col ogy and 

met a bolic dis ease and be com ing Alnylam’s stra te gic part ner for RNAi ther a peu tics. Un der stand ing RNAi 

en ables the ‘switch ing on/off’ of genes and gene si lenc ing, lead ing to the cre ation of a po ten tial new class 

of RNAi ther a peu tics. Takeda is so far Ja pan’s only com pany working in this area and the deal was 

selected as In Vivo Blog’s ‘deal of the year’ for 2008. 

Takeda has been fill ing its on col ogy pipe line through li cens ing deals, in clud ing one in April 2008 with Cell 

Genesys for the pros tate can cer immunotherapy GVAX, al though Takeda ter mi nated de vel op ment in De - 

cem ber 2008 with all com mer cial rights to be re turned to Cell Genesys. As part of the li cense agree ment 

with Amgen in Feb ru ary 2008, Takeda has ac quired rights to de velop and mar ket al most all of Amgen’s 

pipe line (13 prod ucts), ex clud ing Amgen’s main prod ucts which have al ready been li censed to Kirin and 

Daiichi Sankyo, in ad di tion to Amgen’s hu man re sources spe cial iz ing in the de vel op ment of 

biopharmaceuticals. Takeda will pay up to $837 mil lion in upfront and de vel op ment mile stone pay ments. 

The most ad vanced prod uct was Vectibix (panitumumab) for colorectal can cer, now ap proved and gen er - 

at ing block buster sales. The only other prod uct at a late stage of de vel op ment is motesanib (AMG 706) 

for can cer, and said to be one of the main driv ers of the deal for Takeda. Other prod ucts li censed in clude a 

num ber for can cer: AMG 386, AMG 479 and AMG 655; as well as AMG 108 for rheu ma toid ar thri tis and 

AMG 317 for asthma. The li censed prod ucts will strengthen Takeda’s pri or ity fields of can cer and uro log i - 

cal dis eases (12 pro jects un der way in clud ing line extensions) as well as CNS and bone joint disease (11 

projects underway). 

Com pared to most Jap a nese com pa nies, Takeda was pre vi ously rel a tively un-re li ant on in-li cens ing for 

its rev e nues. With three of Takeda’s four block bust ers go ing off-pat ent be tween 2009 and 2012 

(lansoprazole in 2009, pioglitazone in 2011 and candesartan in 2012) how ever, Takeda plans to in vest 

15% of its an nual R&D bud get to ob tain li cens ing can di dates from out side. Takeda in tends to li cense-in 



prod ucts for hyperlipidemia, ath ero scle ro sis, can cer, schizo phre nia, de pres sion, and con sti pa tion-type 

inflammatory bowel syndromes. 

Fu ture Pros pects 

• Chal lenge of pat ent losses with PDUFU de lays 

Takeda pres i dent Yasuchika Hasegawa has ac knowl edged that the next year or two will be a test ing time 

for the com pany while its four main stay global stra te gic prod ucts lose pat ent pro tec tion over the next five 

years and re views of their suc ces sors are de layed. Prevacid (lansoprazole) loses pat ent pro tec tion in No - 

vem ber 2009 fol lowed by Actos (pioglitazone) in 2011 and then the an gio ten sin II re cep tor blocker 

Blopress (candesartan) in 2012 and Leuplin (leuprorelin) in 2014. The pat ent ex pi ra tion of Actos and 

Prevacid alone is ex pected to amount to an nual losses of over Yen500 bil lion in 2009 through 2011 and 

Takeda has said it will work to pri or i tize re sources for launch ing the new prod ucts and deal ing with the dif - 

fi cult sit u a tion. In its 2006-2010 me dium-term man age ment plan, Takeda has set it self a goal of achiev - 

ing sales of in-house eth i cal prod ucts of Yen1.4 tril lion in fis cal 2010 (end ing March 2011), as an in terim 

goal on the way to Yen2 tril lion by the year end ing March 2016. More over, Takeda plans to in vest a tem - 

po rary re cord break ing amount in R&D, al most Yen500 bil lion, al though has stressed that the in crease 

will be tem po rary In Feb ru ary 2009, fol low ing the re lease of its nine-month re sults, Takeda pro jected 

that sales for the full year (end ing March 2009) will reach Yen1.6 tril lion, a 13.5% in crease over the pre vi - 

ous year while net prof its are set to de cline 45.1% to Yen195 billion, incorporating a number of 

Millennium merger related costs. 

Al though the larg est com pany do mes ti cally, Takeda is a min now by global stan dards with sales around a 

quar ter that of Pfizer’s, and Takeda hopes that the lat est ac qui si tions will boost it into the top 15 US phar - 

ma ceu ti cal com pa nies. Re al iz ing this need to grow, Takeda has been among the most ac quis i tive of the 

do mes tic com pa nies in re cent years and its lat est bold ac qui si tion rep re sents the need of Jap a nese 

pharma to es cape from a mar ket pinched by price cuts in search for growth from the US. The strength of 

the Yen ver sus the dol lar has also made US com pa nies par tic u larly at trac tive tar gets and the ac qui si tion 

of Mil len nium came in the midst of a Jap a nese spend ing spree of for eign firms. This started with Eisai’s 

$3.9 bil lion take over of MGI Pharma in the USA in De cem ber 2007 through to Shionogi’s Oc to ber 2008 

$1.4 bil lion merger with Sciele. Eisai’s pur chase closely fol lowed two pre vi ous US in vest ments of 

Morphotek and Ligand that ex panded its on col ogy fran chise while an other ma jor Jap a nese player 

Astellas, pur chased Agensys for $0.5 bil lion in 2007. Takeda’s move to buy into the lu cra tive on col ogy 

set ting re flects other re cent sim i lar strat e gies, in clud ing Eli Lilly’s $6.5 bil lion pur chase of ImClone Sys - 

tems to ob tain Erbitux (cetuximab) and a pipe line of early-stage on col ogy prod ucts. The ac qui si tion of 

Mil len nium has been de scribed as the most sig nif i cant and stra te gi cally transformative deal in Takeda’s 

history and will help it realize its goal of becoming one of the top three oncology companies. 

Al though an a lysts crit i cized the deal for be ing too ex pen sive, six months on, it looks to have been a 

well-planned move as sales of Velcade topped $1 bil lion, boosted by the June 2008 ap proval as a first-line 

ther apy for mul ti ple myeloma. The ad di tion of Velcade may be Takeda’s lone bright spot how ever as the 

pat ent ex pi ra tions of Actos and Prevacid near with lit tle other than Velcade to fill the gap fol low ing un for - 

tu nate missed PDUFU dates for the fol low-on prod ucts, DPP-IV in hib i tor SYR 322 (alogliptin) un til June 

2009, and Kapidex (TAK 390 MR) for pep tic ul cers, which fi nally re ceived ap proval in Jan u ary 2009. This 

ap proval made lit tle im pact on Takeda’s share price and with slow ing US sales, an a lysts are con cerned 

about the risk from de creas ing sales of Actos in the US to gether with the de lays in ap proval of SYR 322 

which could help to off set that risk. Al though the de lay to ap proval of alogliptin, which now lags well be - 

hind Merck’s Januvia is a huge blow for Takeda, ap proval of a pill com bin ing alogliptin with Actos is ex - 

pected in the sec ond half of 2009 which could be a sig nif i cant ad di tion to its di a be tes fran chise. The lat est 

ap prov als of Kapidex and Uloric (TMX 67) for gout (ap proved in Feb ru ary 2009) will give TPNA two new 

drug launches in the first half of 2009 and further strengthen Takdea’s presence in the US. 



Events with Major Potential Impact for Takeda 

EVENT SUMMARY 

Multiple patent expirations Takeda’s four mainstay global strategic products lose patent protection 

over the next five years: Prevacid (lansoprazole) in November 2009 

followed by Actos (pioglitazone) in 2011 and then Blopress 

(candesartan) in 2012 and Leuplin (leuprorelin) in 2014. The patent 

expiration of Actos and Prevacid alone is expected to amount to annual 

losses of over Yen500 billion in 2009 through 2011. 

Transformative Millennium 

acquisition 

TAP buyout to boost US 

status 

Delayed review of 

alogliptin and Actos 

expansion 

Pending launches of 

Kapidex and Uloric in the 

US 

The Yen1 trillion acquisition of Millennium has been described as the 

most significant and strategically transformative deal in Takeda’s history 

and will help it realize its goal of becoming one of the top three oncology 

companies. 

After 30 years together, Takeda decided to dissolve the TAP jv with 

Abbott from mid-2008 and paid $1.5 billion for Abbott’s share of the jv, 

gaining full rights to Takepron and losing Leuplin. The 50% share in TAP 

has been fully integrated into Takeda’s growing stand-alone operation, 

Takeda Pharmaceuticals North America (TPNA) and Takeda hopes its 

presence in the US will be boosted to rank in the top 15. 

The FDA review of alogliptin, the follow-on to Actos, is delayed until June 

2009, a delay of eight months from the original date and it now lags well 

behind Merck &Co’s Januvia (sitagliptin), which has become the ‘gold 

standard’ for the DPP-IV inhibitor class, with new products expected to 

show superiority. Analysts so far seem to be of the opinion that alogliptin 

only offers similar safety and efficacy to Januvia, although Takeda may 

benefit from greater experience in diabetes, as well as approval of a pill 

combining alogliptin with Actos, expected in the second half of 2009. 

The latest approvals of Prevacid (lansoprazole) follow-on Kapidex (TAK 

390MR) for peptic ulcers and Uloric (TMX 67) for gout, approved in 

January and February 2009, will give TPNA two new drug launches in the 

first half of 2009 in the US. 

Blopress expansions Blopress was the best selling pharmaceutical product in Japan in the year 

ending September 2008 according to IMS. Takeda is developing a 

fixed-dose combination of candesartan with the calcium antagonist 

amlodipine in Japan, which will combine two of Japan’s best selling 

drugs. Takeda and AstraZeneca’s combination of candesartan cilexetil 

and hydrochlorothiazide (Blopress Comp) is available in most markets 

worldwide for the treatment of hypertension and approval as Ecard was 

granted in Japan in January 2009. 



� Net Sales 

Financial Review 

In the year end ing March 31 2008, Takeda posted net sales of Yen1,375 bil lion, up 5.3% over the pre vi - 

ous year sales of Yen1,305 bil lion. 

Yen billions 

1,600 

1,400 

1,200 

1,000 

800 

600 

400 

200 

0 

Source: Takeda Annual Reports 

� Net Profit 

Company Sales 

2004 2005 2006 2007 2008 

Net profit was up 5.9% to Yen356 bil lion in fis cal 2007 (end ing March 2008) from Yen336 bil lion the pre vi - 

ous year while op er at ing prof its fell 7.7% to Yen423.1 bil lion, due to in creased R&D costs as so ci ated with 

the Amgen payments. 

Yen billions 

400 

350 

300 

250 

200 

150 

100 

50 

0 


Net Profit 

2004 2005 2006 2007 2008 



� Earnings per Share 

In the year end ing March 31 2008, earn ings per share at Takeda grew by 8.5% to Yen419.0 from 

Yen386.0 the pre vi ous year. 

Yen 

450.0 

400.0 

350.0 

300.0 

250.0 

200.0 

150.0 

100.0 

50.0 

0.0 


� R&D Costs 

Earnings Per Share 

Spend ing on R&D in creased by 42.7% in the year to March 31 2008 to reach Yen276 bil lion, or 20.1% of 

sales, up from Yen193 bil lion (14.8% of sales) in the pre vi ous year. This in crease was par tially due to li - 

cense fees paid to Amgen. 

Yen billions 

300 

250 

200 

150 

100 

50 

0 


2004 2005 2006 2007 2008 

� Sales by Business Sector 

R&D Costs 

2004 2005 2006 2007 2008 

Takeda’s busi ness was pre vi ously clas si fied into four seg ments, but since April 2003 the re struc tur ing and 

divestments of sev eral non-core busi nesses have left the firm with just two seg ments: Pharmaceuticals 

and Other. Within Pharmaceuticals, the com pany splits sales out fur ther into Eth i cal Drugs (split again 

into Do mes tic and Over seas) and Con sumer Healthcare. The Other seg ment rep re sents the man u fac ture 

and sales of lab o ra tory chem i cals and clin i cal di ag nos tic agents, spe cialty chem i cals, beverages and food, 

among others. 



In the year to March 31 2008, the Pharmaceuticals seg ment re corded net sales of Yen1,272 bil lion, up 

5.8% from Yen1,203 bil lion in the year-ear lier pe riod and rep re sent ing 92.5% of to tal sales. Eth i cal drug 

sales grew by 5.8% to Yen1,210.2 bil lion (88% of to tal sales) from Yen1,144.1 bil lion the pre vi ous year, 

of which Yen529.7 bil lion (up 2.9%) was gen er ated in Ja pan (38.5% of to tal sales), and Yen680.6 bil lion 

(up 8.2%) was gen er ated over seas (49.5% of total sales). 

To tal sales of the four global stra te gic prod ucts were: Yen396.2 bil lion for Actos (pioglitazone), up 

17.8%; Yen223.1 bil lion for Blopress (candesartan), up 8.2% Yen148.7 bil lion for Takepron 

(lansoprazole), down 1.4% and Yen124.0 bil lion for Leuplin (leuprorelin) down 2.7%. 

Do mes tic sales of Blopress were Yen137.1 bil lion (up 6.1%); Yen66.4 bil lion for Leuplin (up 3.3%); 

Yen64.8 bil lion (up 11.8%) for Takepron; Yen41.6 bil lion for Actos (up 23.6%) while a 5.2% de cline in 

sales of Basen (voglibose) to Yen52.8 bil lion was re corded due to the en try of generics and other un fa vor - 

able factors. 

The US mar ket saw a 17.7% rise in sales of Actos to $2.79 bil lion while sales of new con sti pa tion drug 

Amitiza more than tri pled its sales to $171 mil lion and Rozerem for in som nia jumped 25% to $111 million 

The Con sumer Healthcare busi ness posted a 5.3% in crease in sales from Yen58.7 bil lion to Yen61.8 bil - 

lion in the 12 months to March 2008, rep re sent ing 4.5% of to tal sales. 

Net sales in the Other seg ment in creased slightly by 0.4% from Yen102.4 bil lion to Yen102.7 bil lion in the 

12 months to March 2008. 

Yen billions 

1,400 

1,200 

1,000 

800 

600 

400 

200 

0 


Sales by Business Sector 

2004 2005 2006 2007 2008 

Pharmaceuticals Other 



� Sales by Geographical Region 

For the year to March 31 2008, sales gen er ated in Ja pan were up 30% over the pre vi ous year to reach 

Yen859 bil lion, com pris ing 62.5% of to tal sales. Sales in Takeda’s sec ond larg est re gion, North Amer ica, 

de clined by 16% in the year un der re view, to Yen358 bil lion and now ac count ing for around one quar ter 

(26%) of Takeda’s rev e nues. Com pris ing 10.7% of to tal sales, sales in Eu rope de clined by 23% to reach 

Yen147 bil lion, while Other Mar kets, com pris ing the re main ing 0.75% of to tal sales, fell by 59% to 

Yen25.0 bil lion in the year to March 31 2008. 

Yen billions 

1000 

900 

800 

700 

600 

500 

400 

300 

200 

100 

0 


Lat est Re sults 

Sales by Geographic Region 

2004 2005 2006 2007 2008 

Japan North America Europe Asia/Other Markets 

In the nine months end ing De cem ber 31 2008, Takeda re ported a 7.2% rise in sales to Yen1,203 bil lion, 

over the equiv a lent pe riod of 2007. Phar ma ceu ti cal seg ment sales in creased 13.4% to Yen1,134 bil lion 

with sales of Eth i cal drugs up 13.9% to Yen1,084 bil lion com pris ing around 40% from Ja pan where Eth i - 

cal drug sales in creased 2% to Yen427.1 bil lion and around 60% of sales came from Over seas, up 18.9% 

to Yen657 billion. 

Sales of in ter na tional stra te gic prod uct Actos (pioglitazone) for di a be tes de creased 4.8% to Yen297.7 bil - 

lion (due to ap pre ci a tion of the Yen; an in crease in US$ was re corded) with sales growth from: pep tic ul - 

cer drug Prevacid (lansoprazole) with global sales up 97.2% to Yen224.4 bil lion (due to con sol i da tion of 

TAP); Blopress (candesartan) up 2.8% to Yen4.8 bil lion and Leuprorelin, up 2.9% to Yen97.8 bil lion. 

Growth in Ja pan was also driven by a 42.3% rise in sales of Enbrel (etanercept) for rheu ma toid ar thri tis 

al though also saw a de cline in sales of di a be tes drug Basen, down 11.8% to Yen37.1 bil lion. In the US, 

the con sol i da tion of TAP and Mil len nium as sub sid iar ies re sulted in the in clu sion of the sales of 

lansoprazole and Velcade (for mul ti ple myeloma), con trib ut ing to over all sales growth. The pat ent ex pi - 

ra tion of lansoprazole in Europe resulted in a decline in sales in this region 

Sales by the Con sumer Healthcare busi ness in creased 3.2% to Yen50.1 bil lion, sup ported by in creased 

sales of Benza (a cold rem edy) and Nicorette for smok ing ces sa tion al though sales of vi ta min tonic 

(Alinamin) drinks were down. Sales by Other Seg ments de creased by 9.5% in the same pe riod to Yen7.2 

billion 

Net prof its of Yen169 bil lion were re corded for the nine months, 24.5% lower than in 2007 while Earn ings 

per Share dropped to Yen206.95 from Yen389.84 in 2007. In vest ment in Re search and De vel op ment 

amounted to Yen207.4 bil lion, 121.8% higher than the pre vi ous year. 



An a lyst Com ment 

In Feb ru ary 2009, an a lysts at Credit Suisse re it er ated a ‘Neu tral’ rat ing and tar get price of Yen4,900 (on 

par with the phar ma ceu ti cal sec tor av er age) to Takeda. Fol low ing the re port of nine month re sults, where 

the Mil len nium ac qui si tion and con sol i da tion re flected in a 12% rise in sales to Yen1,203 bil lion al though 

Takeda re ported a sharp 41% de cline in prof its. Takeda’s full year guid ance has been left un changed and 

the an a lysts are also main tain ing their fore casts, adopt ing a ‘wait and see’ ap proach un til one-time fac - 

tors drop out the pic ture. The strong Yen had a year-on-year neg a tive im pact on sales (Yen55.2 bil lion) 

and net profit (Yen9 bil lion) but the an a lysts be lieve that ex clud ing the for ex im pact, in real terms, sales 

of Takeda’s four stra te gic prod ucts (Actos, Takepron/Prevacid, Blopress and Leuplin) are slow ing, add ing 

that even if full fis cal 2008 (end ing March 2009) guid ance is reached, re cov ery in earn ings from fis cal 

2009 (end ing March 2010) on wards could slow, al though from this time they ex pect a re cov ery in profit 

as in-pro cess R&D and other fac tors wind down. The ap proval of Kapidex, the suc ces sor to Prevacid in the 

US has had vir tu ally no im pact on Takeda’s share price and the an a lysts are con cerned about the risk 

from de creas ing sales of Actos in the US to gether with the de lays in ap proval of SYR 322, which could help 

to off set that risk. Re gard ing the Mil len nium ac qui si tion, the an a lysts com mented that the overall picture 

from this is currently hard to determine but could impact the investment stance. 

An a lysts at Mor gan Stan ley, writ ing in Feb ru ary 2009 main tained their ‘Over weight’ rat ing and ‘At trac - 

tive’ in dus try view with a price tar get of Yen6,800. They com mented that the strong Yen would soften the 

size of the loss for the merged Takeda (with TAP and Mil len nium ac qui si tion). The fo cus will now be on the 

sales trends of Actos and Prevacid, the launches of Kapidex (ap proved in Jan u ary) and TMX 67 for gout 

(ap proved in Feb ru ary) and the ap proval of DPP IV in hib i tor SYR 322 for di a be tes, now de layed un til June 

26, 2009. The lat est ap prov als mean that TPNA will now have two new drug launches in the first half of 

2009 al though the de lay to ap proval of alogliptin, which re ceived a rec om men da tion from the FDA panel 

No vem ber, is a blow for Takeda, al though the an a lysts pointed out one source of light on the pros pects of 

its ap proval from the April 2009 FDA panel for Endocrinologic and Met a bolic Drugs Ad vi sory Com mit tee 

where Novo Nordisk’s GLP1 ag o nist liraglutide will be dis cussed and there is a pos si bil ity that other 

DDP-IV in hib i tors in clud ing alogliptin and AstraZeneca’s saxagliptin may also be discussed given the 

extended discussion period from one to three days. 



Product Portfolio 

In the year to March 31 2008, the Pharmaceuticals seg ment re corded net sales of Yen1,272 bil lion, up 

5.8% from Yen1,203 bil lion in the year-ear lier pe riod and rep re sent ing 92.5% of to tal sales. Eth i cal 

drug sales grew by 5.8% to Yen1,210.2 bil lion (88% of to tal sales) from Yen1,144.1 bil lion the pre vi ous 

year, of which Yen529.7 bil lion (up 2.9%) was gen er ated in Ja pan (38.5% of to tal sales), and Yen680.6 

bil lion (up 8.2%) was gen er ated over seas (49.5% of to tal sales). The Con sumer Healthcare busi ness 

posted a 5.3% in crease in sales from Yen58.7 bil lion to Yen61.8 bil lion in the 12 months to March 2008, 

rep re sent ing 4.5% of to tal sales. Net sales in the Other seg ment in creased slightly by 0.4% from 

Yen102.4 bil lion to Yen102.7 bil lion in the 12 months to March 2008. 

Takeda’s eth i cal drugs busi ness has a very high sales weight of high-in come in-house de vel oped drugs, 

and it is well po si tioned with re gards to ther a peu tic fo cus; it gen er ates much of its sales from the high 

growth di a be tes and on col ogy ar eas, as well as anti-ulcerants; oral antidiabetics; an gio ten sin II an tag o - 

nists; and cephalosporin an ti bi ot ics. Ac cord ing to IMS, in the year end ing Sep tem ber 2008, antidiabetics 

and antiulcerants were Takeda’s lead ing ther a peu tic ar eas, each with around one third (33%) of global 

cor po rate sales. An gio ten sin II an tag o nists gen er ated 11% of sales fol lowed by cytostatic hor mones with 

5.8% and neo plas tic drugs with 2.5%. Its ma jor prod ucts are Prevacid/Takepron (lansoprazole), a pro - 

ton pump in hib i tor; Actos (pioglitazone), an oral agent for di a be tes; the can cer and hor monal prod uct 

Leuplin/Lupron; and the an gio ten sin II inhibitor Blopress/Atacand (candesartan cilexetil) for 

hypertension. 

Per for mance of the four global stra te gic prod ucts in the year end ing March 2008 was as fol lows 

To tal sales were up 18% to Yen396.2 bil lion for Actos (pioglitazone) while US sales of Actos rose 18% to 

$2.8 bil lion; do mes tic sales were Yen41.6 bil lion, up 24%. In the 12-month pe riod to the end of Sep tem - 

ber 2008, Actos was Takeda’s sec ond lead ing in ter na tional phar ma ceu ti cal prod uct, mak ing up 26.7% of 

cor po rate sales, with sales up 10% in fixed rate dol lar terms, ac cord ing to IMS. The launch of Actoplus 

Met (pioglitazone/metformin) in 2005 has also helped the di a be tes & en do cri nol ogy port fo lio main tain a 

strong sales per for mance. Actoplus Met was Takeda’s sixth lead ing prod uct with 3.0% of global cor po rate 

sales, up 55% over the pre vi ous year. The ac qui si tion of Syrrx (USA) in 2005 opened up more av e nues 

for growth within the di a be tes arena, through Takeda gain ing rights to mar ket, de velop and com mer cial - 

ize dipeptidyl peptidase IV (DPP-IV) in hib i tors, which have suc cess fully dem on strated in both pre clin i cal 

and clin i cal tri als the po ten tial to treat Type 2 di a be tes and alogliptin (SYR 322) is now awaiting US 

approval and expected to become a major product for Takeda. 

To tal global sales were down 1.4% to Yen148.7 bil lion for Takepron (lansoprazole) with do mes tic sales up 

11.8% to Yen64.8 bil lion. In the 12-month pe riod to the end of Sep tem ber 2008, lansoprazole 

(Takepron) was Takeda’s lead ing in ter na tional phar ma ceu ti cal prod uct, with 32.1% of cor po rate sales, 

down 3% (fixed dol lar rate) ac cord ing to IMS. Takeda gained full rights to Takepron fol low ing the 

dissolutino of the TAP jv in mid-2008. When the US pat ent on Prevacid ex pires in No vem ber 2009, ge - 

neric com pe ti tion could take 90% of its sales and with it, ac cord ing to some in dus try watch ers, 40% or 

more of Takeda’s prof its. Takeda has launched IV and pe di at ric for mu la tions of lansoprazole, but such is 

the na ture of the PPI mar ket that any gains will be short-lived. The main pro tag o nist at the heart of the 

PPI mar ket com pe ti tion are the cheaper ge neric equiv a lents of AstraZeneca’s omeprazole. Many other 

PPIs are due to lose pat ent pro tec tion in the com ing years and thus will en force fur ther competitive strain 

on the remaining brand name medicines. 

To tal, global sales of Blopress were up 8.2% to Yen223.1 bil lion while do mes tic sales were Yen137.1 bil - 

lion, up 6.1%. Ac cord ing to IMS, Blopress was Takeda’s num ber three in ter na tional phar ma ceu ti cal prod - 

uct in the 12-month pe riod to the end of Sep tem ber 2008, mak ing up 11% of cor po rate sales, up 6% in 



fixed rate dol lar terms. Blopress Comp was Takeda’s num ber nine in ter na tional phar ma ceu ti cal prod uct, 

mak ing up 1.3% of cor po rate sales, up 7% in fixed rate dol lar terms. Blopress was Ja pan’s lead ing prod - 

uct in 2008 ac cord ing to IMS and Takeda is de vel op ing a num ber of extended formulations and 

indications. 

Do mes tic sales of Leuplin were Yen66.4 bil lion, up 3.3%, while to tal global sales reached Yen124.0 bil lion 

(down 2.7%). In the 12-month pe riod to the end of Sep tem ber 2008, ac cord ing to IMS, Enantone was 

Takeda’s num ber four in ter na tional phar ma ceu ti cal prod uct, gen er at ing 6.3% of cor po rate sales, up 1% 

over the pre vi ous year in fixed rate dol lar terms.. De spite Lupron hav ing faced pat ent ex piry in 2004, the 

prod uct is still one of Takeda’s larg est. Lupron is rel a tively im mune to ge neric com pe ti tion, since it is a 

ther a peu tic pro tein and the USA has yet to im ple ment a reg u la tory path way for ge neric biologics. Even in 

Eu rope, which is more ad vanced on the way to reg u la tory ap proval for biosimilars, biologics of fer sig nif i - 

cant im mu nity to ge neric com pe ti tion. Abbott gained rights to this product following the dissolution of the 

TAP jv in mid-2008. 

A 5.2% de cline in sales of Basen (voglibose) to Yen52.8 bil lion was re corded due to the en try of generics 

and other un fa vor able fac tors. In the 12-month pe riod to the end of Sep tem ber 2008, Basen was 

Takeda’s num ber five in ter na tional phar ma ceu ti cal prod uct, mak ing up 3.1% of cor po rate sales, with 

sales down 6% in fixed rate dol lar terms, according to IMS. 

Mil len nium pro vides a huge boost to Takeda’s on col ogy pipe line with a num ber of prom is ing can di dates 

and its main stay mar keted prod uct Velcade (bortezomib), an anticancer proteasome in hib i tor, mar keted 

world wide and in Ja pan by John son & John son, which was re ported to re cord block buster sales in 2008. 

Ac cord ing to IMS, Velcade was Takeda’s eighth lead ing in ter na tional prod uct in the year end ing Sep tem - 

ber 2008 with 2.5% of cor po rate sales, up 40% over the pre vi ous year (fixed-dol lar growth). Velcade 

brought Takeda sales of Yen30.3 bil lion in fis cal 2007 (end ing March 2008) and an a lysts at Mor gan Stan - 

ley (Au gust 2008) fore cast sales of Yen76.7 bil lion by the year ending March 2013 for Takeda. 

The US mar ket saw sales of new con sti pa tion drug Amitiza more than tri pled its sales to $171 mil lion in 

the year end ing March 2008 and in the year end ing Sep tem ber 2008, Amitiza be came Takeda’s eighth 

lead ing in ter na tional prod uct ac cord ing to IMS with 1.4% mar ket share and growth of 66%. 

A po ten tially im por tant prod uct for Takeda is the in som nia treat ment, Rozerem, which was launched on 

the US mar ket in 2005 and sales in the year end ing March 2008 jumped 25% to $111 mil lion. How ever, 

the US in som nia mar ket is now very crowded and is soon to in clude generics of Sanofi-Aventis’ Ambien 

(zolpidem). This may limit the po ten tial for Rozerem in its big gest mar ket which Stilnox/Ambien cur rently 

dom i nates with around one-third of this mar ket al though sales are de clin ing and Rozerem is now in fourth 

position. 

Pharmaceuticals 

� Alimentary Tract and Metabolism Agents 

ACTOPLUS MET (pioglitazone + metformin), a fixed com bi na tion of pioglitazone and the biguanide, 

metformin, was launched for the treat ment of Type 2 di a be tes in the USA in 2005, and is avail able in two 

dos ages of 15mg pioglitazone/500mg metformin, and 15mg/850mg, both given once daily. The prod uct 

was ap proved in Eu rope in Au gust 2006 and launched in the UK as Competact in 2006. It has since been 

launched through out Eu rope and in Oc to ber 2008, Takeda filed for ap proval of Competact in Ja pan. The 

prod uct com petes with GlaxoSmithKline’s (UK) Avandamet, which com bines GSK’s Avandia and 

metformin. In the year end ing Sep tem ber 2008, Actoplus Met was Takeda’s sixth lead ing prod uct with 

3.0% of global cor po rate sales, up 55% over the previous year. 



ACTOS (pioglitazone), an in su lin sensitizer, for use in the ther apy of non-in su lin de pend ent (Type 2) di a - 

be tes, was launched in Ja pan and the USA in 1999. The drug low ers mean blood sugar and glycosylated 

he mo glo bin lev els, and also re duces mean triglyceride lev els whilst in creas ing lev els of ‘good’ HDL cho - 

les terol. Actos is the cor ner stone of Takeda’s strat egy of in creased glob al iza tion. It was the first Jap a nese 

‘block buster’ drug to be mar keted by the orig i na tor in the USA (al beit jointly with li censee Lilly). Actos re - 

ceived four in di ca tions from the FDA: monotherapy, and in com bi na tion with sulfonylureas, metformin or 

in su lin to im prove glycemic con trol in Type 2 di a bet ics. Actos was ap proved in the EU in 2000 for use with 

sulfonylureas or metformin. It has been launched by Takeda in var i ous markets worldwide, some by 

licensees Lilly and Abbott. 

In Au gust 2008, Takeda filed for ap proval of pioglitazone in the USA for use in de lay ing the pro gres sion of 

ath ero scle ro sis. 

Ap proval was granted in Ja pan in De cem ber 2008 for use of pioglitazone in com bi na tion with biguanides 

fol low ing the fil ing in Jan u ary 2007. 

Takeda ap plied for ap proval of orodispersible tab lets of Actos in Sep tem ber 2008, ‘Actos OD tab lets. 

Takeda mar kets Duetact (pioglitazone + glimepiride) in the US and Eu rope; phase III tri als of this 

fixed-dose com bi na tion, were un der way in Ja pan in 2009. 

In Jan u ary 2006, rare cases of macular edema were re ported to the Eu ro pean Med i cines Agency in con - 

nec tion with piogiltazone (Actos) and rosiglitazone prod ucts (GlaxoSmithKline’s Avandia, Avandamet 

and Avandaryl, a new fixed-dose com bi na tion prod uct ap proved and launched in Feb ru ary 2006). The 

agency’s sci en tific com mit tee, the CHMP says that fur ther re view of a pos si ble as so ci a tion is re quired; 

edema was noted as a po ten tial side ef fect in pioglitazone tri als. In May 2007 the FDA re quested a ‘black 

box’ warn ing on the la bel of pioglitazone be cause of data in di cat ing an in creased risk of con ges tive heart 

failure in patients given rosiglitazone. 

Li cens ing: Lilly (USA) has co-pro mo tion rights in the Can ada, the USA, Eu rope, Asia (ex clud ing Ja pan), 

Af rica, Aus tra lia and the Mid dle East. In the USA, Actos is co-pro moted by Lilly and Takeda 

Pharmaceuticals North Amer ica (TPNA). The TPNA sub sid iary has nearly 700 sales rep re sen ta tives de tail - 

ing Actos. In 1999, Takeda agreed to co-mar ket Actos in Ja pan with Novo Nordisk (Den mark). In 2000, 

Takeda granted Abbott (USA) ex clu sive rights to pioglitazone in Ar gen tina, Brazil, Chile, Co lom bia, Ec ua - 

dor, Par a guay, Peru, Uru guay and Ven e zuela. Most li cens ees use the Actos brand name. Takeda re ceived 

mar ket ing approval in South Korea in 2003. 

Clin i cal Data: Takeda has con ducted two phase III tri als (PERI SCOPE) and CHI CAGO (in volv ing over 

500 pa tients) com par ing the ef fects of Actos ver sus glimepiride in pa tients with type 2 di a be tes. The pri - 

mary end points were: ca rotid in tima-me dia thick ness (CIMT) in the CHI CAGO trial and the vol ume of 

plaque build-up in the cor o nary ar ter ies in PERI SCOPE. Actos in hib ited the pro gres sion of ar te rio scle ro sis 

in both tri als and based on the trial results, 

Takeda is eval u at ing pioglitazone in phase III tri als in the USA and Eu rope for its abil ity to de lay the pro - 

gres sion of ath ero scle ro sis. In No vem ber 2006, Takeda re ported re sults from an 18-month, multicenter, 

ran dom ized trial, des ig nated CHI CAGO, con ducted to com pare the ef fects of pioglitazone with 

glimepiride on the pro gres sion of ath ero scle ro sis in 462 pa tients with Type 2 di a be tes. The pro gres sion of 

ath ero scle ro sis was mea sured by ca rotid in tima-me dia thick ness (CIMT), de fined as the thick ness of the 

in ner lin ing of a pa tient’s neck ar ter ies. In ad di tion, the trial as sessed the oc cur rence of car dio vas cu lar 

events and car dio vas cu lar dis ease risk fac tors. Re sults from the trial, con ducted in the USA, showed that 

pa tients treated with pioglitazone had a -0.001mm change in ar te rial thick ness from base line com pared 

with an in crease of 0.012mm in pa tients treated with glimepiride. The re sults also showed a sig nif i cant 

rel a tive change in the max i mum CIMT val ues. Pa tients treated with glimepiride showed a 0.026 in crease 



com pared with 0.002 for the pioglitazone-treated pa tients. At the end of the study, pa tients treated with 

pioglitazone had a re duc tion of 0.33% in A1C lev els, com pared with pa tients treated with glimepiride, 

who had a re duc tion of 0.01%. Treat ment with pioglitazone de creased triglyceride lev els by 13.5% ver - 

sus an in crease of 2.1% in pa tients treated with glimepiride. Pioglitazone-treated pa tients showed an in - 

crease in HDL-C lev els of 12.8% com pared with a de crease of 1.1% in pa tients treated with glimepiride. 

Both treat ment groups showed in creased LDL-C lev els, pioglitazone by 5.8% and glimepiride by 1%. 

Data pre sented in No vem ber 2006 and pub lished in the Jour nal of the Amer i can Med i cal As so ci a tion 

(JAMA) dem on strated that Actos halted the pro gres sion of ath ero scle ro sis as in di cated by ca rotid in - 

tima-me dia thick ness (CIMT), with the anal y sis dem on strat ing a sig nif i cant rel a tive re duc tion in the pro - 

gres sion of CIMT with Actos in pa tients with type 2 diabetes. The 18-month study involved 462 patients 

and found that the drug raised HDL (which seems to protect against heart attacks) levels by about 13%. 

In Sep tem ber 2006, Takeda re ported fur ther anal y ses of data from a Eu ro pean phase III trial of 

pioglitazone, des ig nated PROactive (PRO spec tive pioglitazone Clin i cal Trial In macroVascular Events). 

The ran dom ized, dou ble-blind, pla cebo-con trolled study eval u ated the ef fects of pioglitazone in ad di tion 

to stan dard care treat ment on mor tal ity and macrovascular mor bid ity in 5,238 pa tients with Type 2 di a - 

be tes and macrovascular dis ease. The re sults showed that pioglitazone re duced the in ci dence of strokes 

in pa tients who had al ready ex pe ri enced a stroke from 10.2% to 5.6%. The agent re duced the com bined 

risk of death, myo car dial in farc tion or stroke by 28%, but had no ef fect on sub se quent strokes in pa tients 

who had never ex pe ri enced a stroke. As re ported in Sep tem ber 2005, the trial’s com bi na tion pri mary 

end point of risk of seven macrovascular dif fer ent events was re duced by 10% but had not reached sta tis - 

ti cal sig nif i cance by the end of the trial. The main sec ond ary end point of com bined risk of death, heart at - 

tack and stroke was reduced by 16% in high-risk patients with Type 2 diabetes. 

At the Amer i can Di a betic As so ci a tion 65th An nual Meet ing in June 2005, a num ber of stud ies were pre - 

sented, in clud ing one where Actos showed anti-in flam ma tory ef fects by re duc ing CRP lev els, thought to 

be a marker of in flam ma tion and risk fac tor for car dio vas cu lar dis ease al though anal y sis in 2008 showed 

that this risk was no higher in in di vid u als with ge net i cally de ter mined high CRP lev els. An other study 

showed that Avandia may re duce blood pres sure in com bi na tion with a sulfonylurea or with metformin 

(where it was also shown to re duce microalbuminuria); re sults re leased the pre vi ous month (pub lished in 

‘Cir cu la tion’) re vealed that Actos re duced ca rotid ar tery intimamedia thick ness (IMT), CRP lev els and 

blood pres sure as well as in su lin re sis tance, all of which con trib ute to the over all risk for car dio vas cu lar 

dis ease. Data pre sented at the Amer i can Col lege of Car di ol ogy meet ing in March 2005 showed that Actos 

sig nif i cantly re duced neointima for ma tion af ter stent im plan ta tion with out af fect ing met a bolic pa ram e - 

ters in 50 non-di a betic pa tients. While pre vi ous stud ies into the role of thiazolidinedione antidiabetics 

(TZDs), in clud ing Avandia, in di a betic pa tients have led to un cer tainty, this study showed that Actos may 

ex hibit pro tec tive ef fects on the vessel wall. More studies are required however to see how this can be 

translated into clinical benefits. 

Re sults of an other (24-week) study, in volv ing 802 di a betic pa tients, were pub lished in Di a be tes Care in 

June 2005, dem on strat ing that Actos im proved com po nents of di a betic dyslipidemia to a sig nif i cantly 

greater ex tent than Avandia. Switch ing pa tients tak ing a statin from Avandia to Actos was also re ported 

(from the Com ple ment study) to pro duce ben e fits be yond those re sult ing from tra di tional cho les terol 

low er ing statin therapy in key lipid parameters. 

The first di rect com par i son of Actos and GlaxoSmithKline’s (GSK, UK) Avandia in type 2 di a bet ics showed 

that Actos is su pe rior at con trol ling lipid lev els. The re sults, pre sented at the Amer i can Heart As so ci a tion 

meet ing in New Or leans in No vem ber 2004, con firmed pre vi ous sug ges tions that there may be dif fer - 

ences be tween the two prod ucts in terms of their lipid pro files. This could have im pli ca tions for the risk of 

car dio vas cu lar dis ease in long-term us age and would thus in flu ence doc tor’s pre scrib ing choices. Con fir - 

ma tion of a ben e fit in terms of car dio vas cu lar out comes would be a big as set for Actos. Actos was also 

shown to re duce the thick ness of the ca rotid ar tery in type 2 diabetics compared to glimepride, an older 

drug. 



In July 2004, fur ther de tails of the large-scale Eu ro pean clin i cal trial to as sess the ef fect of pioglitazone on 

car dio vas cu lar dis ease pro gres sion in type 2 di a bet ics were re leased. 5,238 pa tients across 19 coun tries 

were en rolled into the PROactive (pro spec tive pioglitazone clin i cal trial in macrovascular events) trial. 

While other stud ies have dem on strated that sus tained glycemic con trol im prove ments can sig nif i cantly 

re duce the risk of some microvascular com pli ca tions, PROactive is con cen trat ing more on macrovascular 

ben e fits. The aim is to see if any pos i tive ef fects on risk fac tors (through mark ers such as atherogenic 

lipids and C-re ac tive pro teins) lead to real re duc tions in car dio vas cu lar events and mor tal ity/mor bid ity in 

what is a high-risk pop u la tion. Up to 45 mg daily of pioglitazone or pla cebo are be ing given as add-on 

ther apy to ex ist ing di a be tes man age ment re gimes, in clud ing diet/ex er cise and other med i ca tion 

(non-thiazolidinedione oral drugs with or with out in su lin). In ves ti ga tors are keep ing glycemic con trol 

within the In ter na tional Di a be tes Fed er a tion’s (IDF) Eu ro pean guide lines (HbA1c.5%), and to give 

lipid-low er ing and/or antihypertensive therapy as needed, also as per IDF Europe guidelines. The study is 

due for completion in 2005. 

In July 2004, find ings ap peared in that month’s is sue of Di a be tes Care show ing that type 2 di a bet ics who 

take two drugs in com bi na tion with in su lin can ef fec tively reg u late their blood sugar lev els with out the 

com mon side-ef fect of weight gain, ac cord ing to a study by re search ers at UT South west ern Med i cal Cen - 

ter, Dal las. This is the first study to an a lyze the safety and ef fec tive ness of tri ple ther apy us ing in su lin, 

metformin, and a drug in the thiazolidinedione group. The 28 pa tients who used tri ple ther apy re duced 

their blood sugar lev els be low 7% (the limit sug gested by the ADA) with out in creas ing in su lin. Pa tients 

who took the ther apy in a par tic u lar or der, with the thiazolidinedione ad min is tered af ter a pe riod of in su lin 

and metformin use, ac tu ally showed a slight de crease in weight, along with low ered blood sugar. Al most 

60% of pa tients, regardless of the order of use, reduced HbAlc levels below 6%. 

In June 2004, re sults from a long-term study us ing pioglitazone alone and in com bi na tion with other oral 

antidiabetics were pre sented at the Amer i can Di a be tes As so ci a tion’s (ADA) 64th An nual Sci en tific Ses - 

sions. These stud ies, which were con ducted over a two-year pe riod, com pared the ef fects of Actos ei ther 

alone or in com bi na tion with two other com monly used oral antidiabetics: a sulfonylurea (gliclazide) and 

metformin. Re sults showed that, whether com bined with metformin or sulfonylurea, the ad di tion of Actos 

pro duced the great est re duc tion in fast ing in su lin; de creases were sus tained over the two years. At 104 

weeks, changes in se rum in su lin lev els from base line for the two arms of the study sug gests a re duced 

de mand on the pan cre atic beta cells. Actos may also tar get spe cific ab nor mal i ties as so ci ated with di a betic 

dyslipidemia and may also lower A1C lev els. The drug was also shown to lower blood pressure in 

hypertensive patients with type 2 diabetes. 

Pat ents: The US pat ent for Actos is valid un til 2011 with cer tain com po si tions (in com bi na tion) cov ered 

un til 2016, but this has not pre vented a num ber of ge neric com pa nies from chal leng ing with ANDA fil ings. 

In Feb ru ary 2006, Teva gained ten ta tive ap proval from the FDA of its ge neric ver sion of pioglitazone (tab - 

let and oral forms in 15, 30 and 45mg), and in the same month, Takeda won its pat ent bat tle with ANDA 

fil ers Mylan and Alphapharm in a US dis trict court pre vent ing them from sell ing ge neric cop ies un til the 

pat ents ex pire in 2011. Takeda was then awarded at tor ney’s fees from the two com pa nies in Sep tem ber 

2006. Takeda filed ac tions against Mylan, Ranbaxy and Wat son in Oc to ber 2003 and then Alpharma in 

March 2004. In March 2007, a US judge or dered Mylan and Alphapharm to pay a com bined $16.8 mil lion 

in le gal fees to Takeda af ter win ning the pat ent dis pute and the ap peal was over ruled in Jan u ary 2009 af - 

ter Takeda won a US pat ent case over active ingredients against Alphapharm in April 2008. 

Lifecycle Man age ment: In Jan u ary 2007 Takeda re ceived a pos i tive opin ion in Eu rope from the CHMP 

rec om mend ing that the com bi na tion of Actos and In su lin be ap proved for the treat ment of pa tients with 

type 2 di a be tes in whom glycemic con trol is in suf fi cient on in su lin alone and metformin is con tra in di cated 

or not well tol er ated. In June 2007 a sim i lar fil ing for use in com bi na tion with insulin was filed in Japan. 

In De cem ber 2005, Takeda filed for ap proval in Eu rope for the use of Actos to re duce the risk of 

macrovascular events in pa tients with Type 2 di a be tes and pre-ex ist ing macrovascular disease. 



The drug has also com pleted phase III tri als to de lay the pro gres sion of ath ero scle ro sis in the USA (see 

Clin i cal Data), and filed for ap proval in 2008. 

In Oc to ber 2008 Takeda filed for ap proval in Ja pan of a fixed-dose com bi na tion of pioglitazone with 

metformin for type II di a be tes and in the same month in Eu rope for a fixed-dose com bi na tion of 

pioglitazone with ex tended-re lease metformin. In 2004, Takeda gained ex clu sive world wide mar ket ing 

rights to a com bi na tion of Actos and Andrx’s (USA) Fortamet (sus tained re lease metformin). In March 

2006, Takeda sub mit ted an NDA for this com bi na tion to the FDA. The com bi na tion prod uct will be man u - 

fac tured by Andrx, but ex clu sive mar ket ing rights will be held by Takeda, who will be re spon si ble for reg - 

u la tory ap prov als. Andrx re ceived $10 mil lion as an ini tial pay ment, and is el i gi ble for additional 

milestone, royalty and performance payments. 

Takeda has been con duct ing phase III tri als of pioglitazone in com bi na tion with the DPP-4 in hib i tor 

SYR-322 in the US and Eu rope and in Sep tem ber 2008 filed an NDA for a fixed-dose com bi na tion drug. 

Ap proval is ex pected no ear lier than mid-2009. The fil ing was sup ported by data from two phase III stud - 

ies in volv ing 2,000 pa tients world wide who did not achieve glycemic tar gets with diet and ex er cise or 

metformin alone. The com bi na tion was re ported to sig nif i cantly im prove glycemic con trol as well as pa - 

ram e ters re lated to beta cell func tion/in su lin re sis tance and be generally well tolerated. 

Pat ents: A su preme court in the US, in March 2008, up held the va lid ity of Takeda’s pat ent un til 2011, fol - 

low ing a pe ti tion from Alphapharma. 

Com pe ti tion: In the 12-month pe riod to the end of Sep tem ber 2008, ac cord ing to IMS, Actos was the 

num ber one drug in the oral antidiabetic (A10B) ther apy class, with a 28.1% mar ket share and 9% 

growth in dol lar terms. Merck &Co’s new dipeptidyl peptidase in hib i tor Januvia (sitagliptin) has stormed 

in at sec ond place af ter its first full year on the mar ket with 8.7% of the mar ket and growth of 178% over 

the pre vi ous year. GSK’s Avandia (rosiglitazone) has fallen to third place with 8.1% mar ket share as 

sales tum bled down by 52%, while its Avandamet fell 16% to fifth place with 4.2% share. Amaryl 

(glimepiride) from sanofi-aventis sat in fourth place with 8.1% of the market, down 52%. 

Actos’ main ri val is GSK’s Avandia, first launched in the USA in 1999 and is now sold in many world mar - 

kets. Al though they be long to the same class and both al ready carry the warn ing stat ing in creased risk of 

con ges tive heart fail ure since mid-2007, Actos has re cently bene fited from Avandia’s plum met ing sales 

due to fur ther safety con cerns. In No vem ber 2007, the FDA an nounced the ad di tion of a ‘black box’ warn - 

ing on Avandia for an in creased risk for heart at tacks in some pa tients, but not death due to in suf fi cient 

ev i dence fol low ing a re port by the New Eng land Jour nal of Med i cine. The Sep tem ber 2007 re port said that 

Avandia in creased the risk of heart at tacks while Actos ap pears to cut the risk of heart at tack, stroke and 

death. The new warn ing will also ap ply to GSK’s other prod ucts Avadaryl and Avandamet and GSK is to do 

a study to pro vide clearer an swers to the safety ques tions sur round ing Avandia, ex pected to take as long 

as four or five years to com plete. A pre vi ous re port from the New Eng land Jour nal of Med i cine in May 2007 

found 43% and 64% greater risk re spec tively in heart at tack and cardiovascular related death from 

patients taking Avandia. 

An a lysts at Mor gan Stan ley an tic i pate that the black box warn ing for Avandia and not Actos will clearly 

dis tin guish the drug safety pro files. In De cem ber 2007, how ever, JAMA pub lished a fur ther study show - 

ing that pa tients aged over 66 years show an in creased risk of de vel op ing a num ber of car dio vas cu lar ad - 

verse events on tak ing thioglitazones over other di a be tes drugs. Anal y sis of the 150,000 pa tients on the 

drugs for an av er age of four years, showed 40% in creased risk of heart at tack; 60% in creased con ges - 

tive heart fail ure and 29% risk of death com pared to those on other di a betic treat ments. The FDA has 

asked doc tors to ac knowl edge the po ten tial risks and fur ther anal y sis is be ing con ducted to determine if 

the findings are limited to Avandia. 



Re cent meta-anal y ses have sug gested that the risks as so ci ated with rosiglitazone may be higher than 

those as so ci ated with pioglitazone, par tic u larly when used in el derly pa tients. In No vem ber 2008, a ret - 

ro spec tive study pub lished in the Ar chives of In ter nal Med i cine, which looked at about 14,000 pa tients on 

Medicare (i.e., older than 65) who were pre scribed Avandia be tween 2000 and 2005, and com pared 

these pa tients to 14,000 who were get ting Actos, found that the pa tients who started on Avandia had a 

15% higher ‘deaths from all-cause’ rate than the Actos group. The Avandia group had a 13% higher rate 

of CHF, but no dif fer ence in the in ci dence of strokes and MI (Avandia in pre vi ous stud ies was linked with 

an in creased in ci dence of MI). The au thors con cluded that al though pre vi ous stud ies have in di cated that 

the in creased risk with rosiglitazone use re sides pre dom i nantly in car dio vas cu lar out comes, the above 

study sug gests that dif fer ences in all-cause mor tal ity risk may be even more im por tant to con sider in el - 

derly pa tients. Re gard ing the fact that no dif fer ence in MI be tween the two groups was ob served, the re - 

search ers said that since 75% of di a bet ics die from heart-re lated causes, the re search ers think MIs and 

strokes likely contributed to the overall increased deaths in the Avandia group 

In Oc to ber 2008, new rec om men da tions from ex perts at the Eu ro pean As so ci a tion for the Study of Di a - 

be tes and the Amer i can Di a be tes As so ci a tion no lon ger backed the use of Avandia for treat ing Type 2 di a - 

bet ics: the rec om men da tions have re tained a ref er ence to the use of Actos, how ever. In the same month, 

there was a call by the US ad vo cacy group Pub lic Cit i zen for Avandia to be banned due to a high num ber of 

re ports of liver fail ure and death in patients taking the drug. 

In creased risk of frac tures in women was also re ported in 2007 with Actos in anal y sis of data con cern ing 

over 15,000 pa tients; fur ther anal y sis re ported in 2008 re vealed that the drugs could dou ble this risk. 

GSK had pre vi ously warned the FDA of sim i lar risk with Avandia. Fur ther ev i dence in 2007 has as so ci ated 

Avandia with links to os teo po ro sis from a com bi na tion of de creased bone for ma tion and in creased bone 

re sorp tion al though re sults are in con clu sive to date. As such, the FDA has ad vised healthcare pro fes sion - 

als to con sider the risk when pre scrib ing these prod ucts. Re sults of an other study in 2008 showed a dou - 

ble or tri ple in crease of bone frac ture in pa tients tak ing the thiazolidinediones over con trol pa tients and 

re search ers be lieve that as well as sen si tiz ing the body to in su lin, these drugs also stim u late bone 

resorption, making the bones vulnerable to fracture. 

Byetta’s (exenatide) im pact on blood glu cose con trol, and par tic u larly its weight re duc ing prop er ties, 

gives it a pro file that is very at trac tive to doc tors. Mor gan Stan ley an a lysts think that the DPP-IV in hib i tors 

are more likely to be used in ear lier stage dis ease and there fore should not be seen as di rectly com pet i tive 

with drugs like Avandia/Byetta. How ever, MS be lieves that the DPP-IV class has sec tor re shap ing po ten - 

tial in the same way as PPIs did in the GI field and ACE in hib i tors did in car dio vas cu lar and statins did in 

cholesterol. 

The FDA is now call ing for higher safety stan dards in ap prov ing di a be tes drugs and the risk ben e fit pro file 

of other di a betic drugs is also in ques tion, in clud ing Merck & Co’s DPP4 in hib i tor Januvia 

(sitagliptin),which was the first in class fol low ing its US launch in Oc to ber 2006, and is now the ‘gold stan - 

dard’ for this class and has had a sig nif i cant im pact. Merck & Co has also launched a com bi na tion prod uct 

Janumet (sitagliptin + metformin) in some mar kets. Januvia has been launched in the USA and across 

Eu rope and is pend ing ap proval in Ja pan and many other mar kets. Januvia has per haps bene fited from 

the neg a tive pub lic ity for Avandia, par tic u larly as it is re ported to have a better side ef fect pro file than 

TZD drugs and is as so ci ated with a lack of weight gain. How ever, on the neg a tive side, the DPP-IV path - 

way is com plex and long-term prod uct use is as yet un tested. If ap proved, Takeda’s SYR 322 will be the 

sec ond DPP-4 in hib i tor af ter Januvia. Novartis’ Galvus (vildagliptin) has been ap proved in the EU where 

it is now be ing rolled out, but has faced safety con cerns in the US and fol low ing safety stud ies, fil ing may 

now be de layed un til 2010. Galvus was filed for ap proval in Ja pan in April 2008A fil ing in Ja pan is ex pected 

in April 2008. In 2007, an ar ti cle in the New Eng land Jour nal of Med i cine ques tioned the safety data avail - 

able for the drugs Januvia and Galvus writ ing that it was surprising the FDA decided to clear Januvia given 

the questionability of safety data. 



In April 2007, the Brit ish Med i cal Jour nal warned of ‘turn ing healthy peo ple into pa tients’ through use of 

drugs such a s rosiglitazone in the pre ven tion of di a be tes when life style changes can be just as ef fec tive 

as well as safer and cheaper. Re sults of one Takeda-spon sored, 600-pa tient study showed that ‘pre-di a - 

betic’ sub jects tak ing pioglitazone were much less likely to de velop di a be tes than placebo patients. 

Sales/An a lyst Com ment: In the year to March 31, 2008, ac cord ing to Takeda, do mes tic sales of Actos 

were Yen41.6 bil lion, up 23.6%. To tal global sales were up 17.8% to Yen396.2 bil lion. In the 12-month 

pe riod to the end of Sep tem ber 2008, Actos was Takeda’s sec ond lead ing in ter na tional phar ma ceu ti cal 

prod uct, mak ing up 26.7% of cor po rate sales, with sales up 10% in fixed rate dol lar terms, ac cord ing to 

IMS. Mor gan Stan ley an a lysts, (Au gust 2008), ex pect to tal sales to peak at Yen513.5 bil lion by the year 

to March 2011, fall ing steeply to Yen321.5 billion two years later. 

ALINAMIN vi ta min and tonic prod ucts: Alinamin is Takeda’s best-sell ing OTC brand. The range in cludes 

Alinamin A25 (vi ta min B1 tab lets), Alinamin EX (a vi ta min E-for ti fied vi ta min B1, B6 and B12 com - 

pound), Alinamin V, a 50ml vi ta min B com plex health tonic drink, launched in 1987, Alinamin Dy - 

namic, a 100ml tonic drink, launched in 1996, and New Alinamin A, which con tains more vi ta min B6 

and B12 than the orig i nal prod uct, launched in 1999. 

AMITZA (lubiprostone), a func tional fatty acid and chlo ride chan nel opener for the treat ment of cer tain 

mo til ity-as so ci ated gas tro in tes ti nal dis or ders like Ir ri ta ble Bowel Syn drome (IBS), launched in the USA in 

April 2006. Takeda Pharmaceuticals Amer ica and Sucampo (USA) jointly mar ket the drug in the US. The 

prod uct should be taken twice-daily with food help ing to pre vent nau sea, one of the re ported side ef fects 

(along with head ache, di ar rhea, ab dom i nal pain and dis ten sion) and safety in preg nancy is not yet es tab - 

lished. It was orig i nally de vel oped by Sucampo and li censed-out to Takeda for the USA and Canada. 

Lubiprostone was ap proved by the FDA in April 2008 in the USA in adults (fe male) for con sti pa tion-pre - 

dom i nant ir ri ta ble bowel syn drome (IBS-C) fol low ing the fil ing of a sNDA in July 2007. The sNDA was 

based on the re sults of three stud ies in volv ing over 1,500 adults dem on strat ing that a sta tis ti cally sig nif i - 

cant re sponse was twice as likely in pa tients re ceiv ing 8 mcg lubiprostone twice daily over pla cebo over 

12 weeks and this ef fi cacy was con tin ued over 52 weeks with sim i lar adverse events to the placebo 

group. 

Li cens ing: Un der the terms of a 2004 deal, Takeda ac quired rights to mar ket lubiprostone in the USA 

and Can ada, with Sucampo hav ing an op tion to jointly mar ket in these coun tries. Takeda also ac quired an 

op tion to mar ket lubiprostone in other ter ri to ries such as Ja pan and Eu rope. Sucampo will re ceive from 

Takeda ini tial and mile stone pay ments worth up to $210 mil lion, and post-launch roy alty pay ments. 

Takeda will fund a ma jor part of costs to de velop the agent for chronic con sti pa tion, con sti pa tion-pre - 

dom i nant ir ri ta ble bowel syn drome and other gas tro in tes ti nal in di ca tions. The fil ing in July 2007 ini ti ated 

a pay ment from Takeda to Sucampo. Ex clu sive man u fac tur ing and sup ply of the prod uct will be carried 

out by Sucampo’s subsidiary R-Tech Ueno. 

In Feb ru ary 2007, Takeda and TAP agreed to jointly pro mote the prod uct in the USA; the TAP (jv with 

Abbott) was con cluded in May 2008. 

Lifecycle Man age ment: In De cem ber 2008, Takeda/Sucampo con firmed that en rol ment for phase III 

tri als in the USA in Opioid-In duced Bowel Dys func tion (OBD), had com pleted with a to tal of 875 patients. 

Clin i cal Data: The NDA, filed in March 2005, in cluded data from two piv otal, dou ble-blind, pla cebo-con - 

trolled phase III tri als of lubiprostone, which dem on strated that ap prox i mately 60% of pa tients ex pe ri - 

enced spon ta ne ous bowel move ment within 24 hours of treat ment with the agent. 

Sucampo re ported in Oc to ber 2008 data from three open-la bel, long-term (six and 12 months) clin i cal 

tri als of lubiprostone in pa tients with chronic id io pathic con sti pa tion (CIC). The tri als were con ducted be - 

tween No vem ber 2001 and Jan u ary 2005: the first trial was a 24-week, 308-pa tient, open-la bel ex ten - 



sion to a four-week dou ble-blind, piv otal trial; the sec ond trial was a 48-week, 250-pa tient, open-la bel 

trial, 82 of whom were in volved in a seven-week ran dom ized with drawal study pe riod be fore the open-la - 

bel phase of the trial; and the third trial was a 48-week, open-la bel trial in 325 treat ment-na ive pa tients. 

Pa tients were given twice-daily, oral lubiprostone 24 mcg for six or 12 months, as re quired; they then re - 

mained on a daily dos ing sched ule or stopped lubiprostone ther apy de pend ing on their per ceived needs. 

Pa tients could re turn to lubiprostone ther apy if re quired, but were to re start dos ing of lubiprostone at 24 

mcg twice daily. The daily dose could be al tered by in ves ti ga tors in re sponse to pharmacodynamic events 

or treat ment-re lated ad verse events. Pe ri odic res cue med i ca tion use was per mit ted. Re sults from the tri - 

als showed that lubiprostone dem on strated good tolerability and sig nif i cantly im proved symp toms (sub - 

jec tively as sessed) of CIC. There were sta tis ti cally sig nif i cant im prove ments in sec ond ary end points such 

as con sti pa tion se ver ity, abdominal bloating and abdominal discomfort, assessed by patients using a 

five-point scale. 

Com pe ti tion: Most pa tients with chronic con sti pa tion are treated with di etary fi ber, os motic lax a tives 

and bulk ing agents be fore try ing phar ma ceu ti cal treat ments. Amitiza is the first se lec tive chlo ride chan - 

nel ac ti va tor to be ap proved and ac cord ing to Takeda, the only one in de vel op ment, work ing to in creased 

fluid se cre tion and mo til ity in the in tes tine speed ing up the pas sage of stool and thus re duc ing symp toms 

of con sti pa tion. Most other prod ucts in this area are tar geted at opioid-in duced con sti pa tion. Amitiza will 

com pete with Novartis’ 5HT4 par tial ag o nist, Zelnorm/Zelmac (tegaserod maleate), ap proved in 2004 

in the USA, and the first prod uct tar geted at this mar ket. Ac cord ing to IMS, Zelmac lost its pre vi ous po si - 

tion as the lead ing gas tro in tes ti nal sensorimotor mod u la tor in the 12-month pe riod to the end of Sep tem - 

ber 2008, with sales down 94% in fixed rate dol lar terms. It now sits in sec ond place, with 45.2 % of the 

mar ket, be hind its only ma jor com pet i tor, also launched in the US in 2004, GlaxoSmithKline’s Lotronex 

(alosetron) with a 51.7% mar ket share (sales up 43% in fixed rate dol lar terms), and some ge neric ver - 

sions of tegaserod sold in In dia, Ban gla desh, Pa ki stan, Chile, Peru and Co lom bia. Due to prob lems with 

side ef fects, Zelnorm was with drawn in 2000. It has been re-launched in the USA in 2002 for lim ited use 

(in women with se vere di ar rhea-pre dom i nant IBS who have not re sponded to con ven tional treat ment 

and whose symp toms can not be ac counted for by other gas tro in tes ti nal dis or ders). Lotronex tar gets di - 

ar rhea-pre dom i nant IBS (and is a 5HT3 an tag o nist), while Zelmac tar gets con sti pa tion-pre dom i nant IBS 

(and is a 5HT4 agonist). In 2007, Prometheus Laboratories (USA) gained exclusive rights to Lotronex in 

the USA. 

Sales/An a lyst Com ment: Sales in the year end ing March 2008 more than tri pled to Yen19.5 bil lion. In 

the year end ing Sep tem ber 2008, Amitiza be came Takeda’s eighth lead ing in ter na tional prod uct ac cord - 

ing to IMS with 1.4% mar ket share and growth of 66%. An a lysts at Mor gan Stan ley, re port ing on Takeda 

in Au gust 2008, es ti mates sales of Yen36.8 bil lion in the year ending March 2013. 

BASEN (voglibose), an orally ac tive al pha-glucosidase in hib i tor, was launched in Ja pan in 1994 for the 

con trol of post-pran dial hyperglycemia in di a betic pa tients. Li censee CJ Corp (for merly Cheil, South Ko - 

rea) has launched the prod uct in South Ko rea and the prod uct is also avail able in Thai land and the Phil ip - 

pines. In 2004, Takeda launched a fast dis in te grat ing tab let for mu la tion of voglibose in Ja pan. It was also 

in phase III tri als in Ja pan for im paired glu cose tol er ance and filed for ap proval in De cem ber 2007. Re sults 

re leased in May 2008, dem on strated a 40.5% re duc tion in on set of type II di a be tes and 53.9% in crease 

in achieve ment of nor mal iza tion of oral glu cose tol er ance test com pared with pla cebo, al though 

Voglibose-treated pa tients were more likely to suf fer ad verse events but none serious and overall safety 

was comparable. 

In 2003, new warn ings were added at the re quest of the Jap a nese Min is try of Health, Wel fare and La bor 

re gard ing the risk of hepatic side ef fects in clud ing fulminant hep a ti tis and jaun dice. Voglibose had been in 

phase III tri als in the USA and was pend ing ap proval in Eu rope with li censee Abbott (USA) in 2000, but 

Abbott re turned all rights to Takeda in 2002. In June 2006, Takeda an nounced that it had dis con tin ued 

de vel op ment of voglibose for the European and US markets. 



Clin i cal Data: Voglibose acts by im prov ing glu cose tol er ance and re duc ing the in crease in blood glu cose 

fol low ing su crose or starch in take. The drug’s mech a nism is unique in that it de lays/in hib its glu cose ab - 

sorp tion in the small in tes tine, and thereby re duces the rapid rise of blood glu cose lev els af ter meals. It 

acts by block ing an en zyme re spon si ble for de ac ti vat ing a fur ther en zyme in volved in glu cose me tab o - 

lism. It does not di rectly cure di a be tes but is ex pected to im prove blood glu cose lev els and hence slow the 

prog ress of the dis ease and pre vent the de vel op ment of chronic di a betic com pli ca tions, such as neu rop a - 

thy. Basen’s mech a nism is ex pected to al low the drug to be used by pa tients un der go ing dietetic 

treatment as well as those on drug therapies, such as insulin. 

Lifecycle Man age ment: Voglibose was filed for ap proval in Ja pan in De cem ber 2007 for im paired glu - 

cose tol er ance (IGT); no drug in Ja pan is cur rently ap proved for this indication. 

Com pe ti tion: In the year end ing Sep tem ber 2008, Basen was Ja pan’s lead ing oral di a betic ac cord ing to 

IMS with 28% share of do mes tic sales, down 6% (fixed dol lar rate) over the pre vi ous year. Takeda’s 

Actos (pioglitazone) took sec ond place with 25.1% and 22% growth while Amaryl (glimepiride) took 

third place with 13.3% (up 10%). 

Novartis re leased re sults in May 2008 show ing that its DDP-IV in hib i tor Galvus (vildagliptin), await ing ap - 

proval in Ja pan, was twice as likely to re duce HbA1c lev els to 6.5% of less in Jap a nese di a betic pa tients 

than voglibose, which is avail able ge ner i cally in Ja pan and is one of the lead ing first-line ther a pies for type 

2 diabetes. 

Sales/An a lyst Com ment: In the year to March 31 2008, ac cord ing to Takeda, do mes tic sales of Basen 

were Yen52.8 bil lion, down 5.2%, partly due to ge neric in fil tra tion. In the 12-month pe riod to the end of 

Sep tem ber 2008, Basen was Takeda’s num ber five in ter na tional phar ma ceu ti cal prod uct, mak ing up 

3.1% of cor po rate sales, with sales down 6% in fixed rate dol lar terms, ac cord ing to IMS. Mor gan Stan ley 

an a lysts (Au gust 2008), fore cast that do mes tic sales have peaked and will grad u ally de crease to Yen37 

billion by the year ending March 2013. 

DUETACT (pioglitazone + glimepiride) a com bi na tion of pioglitazone with the sulfonylurea com pound, 

glimepiride, was ap proved by the FDA for the treat ment of Type 2 di a be tes in July 2006, and launched in 

the USA in No vem ber 2006. The prod uct is avail able in two dos ages con sist ing of 30mg/2mg and 

30mg/4mg of pioglitazone and glimepiride, re spec tively. Glimepiride acts to in crease pan cre atic in su lin 

pro duc tion. In Jan u ary 2007, EMEA ap proval of the fixed com bi na tion for the treat ment of Type 2 di a be - 

tes was re ceived for the prod uct, to be named Tandemact in Eu rope. A com bi na tion of pioglitazone and 

glimepiride was launched in Mex ico un der the name Diaberil by Rimsa (Mex ico) in June 2006. Phase III 

tri als of this fixed-dose com bi na tion, Duetact (pioglitazone + glimepiride) were underway in Japan in 

2009. 

GASMOTIN (mosapride ci trate) is a 5HT4 ag o nist with gastroprokinetic prop er ties. It was orig i nally de - 

vel oped by Dainippon (now Dainippon Sumitomo) and launched in Ja pan in 1998, as Gasmotin, for re - 

duc ing the symp toms of chronic gas tri tis, such as heart burn. Dainippon de scribes mosapride as the first 

se lec tive se ro to nin 5-HT4 re cep tor ag o nist that en hances gas tro in tes ti nal mo til ity. It has been launched 

in Ar gen tina un der the trade names Mosar and Intesul by Phoe nix and Deta, re spec tively. Mosapride 

was also launched in Cen tral Amer ica, and China by Dainippon Sumitomo in 2001. In 2001, it was 

launched in Peru by Tecnofarma as Reflucil. 

Li cens ing: In 2001, Takeda gained rights to de velop and mar ket mosapride world wide, ex clud ing Ja - 

pan, China, Tai wan and South Ko rea (where it is sold by Daewoong). Mosapride was pre vi ously li censed 

to AstraZeneca (UK) for the USA and Eu rope, but this deal was ter mi nated. In April 2006, Dainippon 

Sumitomo and Eisai signed an agree ment un der which Eisai ac quires de vel op ment, man u fac ture and 

mar ket ing rights to mosapride in 10 Asian coun tries, in clud ing coun tries be long ing to the As so ci a tion of 

South East Asian Na tions (ASEAN) where it is await ing approval and being rolled out. 



Com pe ti tion: In the year end ing Sep tem ber 2008, Gasmotin was the world’s lead ing Gastroprokinetic 

ac cord ing to IMS with 13.7% of global sales, up 5% over the pre vi ous year. John son & John son/Kyowa 

Hakko’s Motilium (domperidone) was in sec ond place with 13.3% (down 1%) fol lowed by 

Pfizer/Mitsubishi Tanabe Pharma’s Debridat (trimebutine) with 5.9% (down 11%). 

GLUFAST (mitiglinide), an antidiabetic po tas sium chan nel in hib i tor de signed to sup press post-pran dial 

hyperglycemia. In May 2004, Kissei and li censee Takeda launched Glufast in Ja pan for the treat ment of 

Type 2 diabetes. 

Li cens ing: Mitiglinide was li censed-in from Kissei in 2002 for co-mar ket ing in Ja pan. 

Lifecycle Man age ment: The com pound was filed for ap proval in Ja pan in April 2007 as a con com i tant 

ther apy with an in su lin sensitizer. 

Com pe ti tion: In the year end ing Sep tem ber 2008, Glufast was Ja pan’s sixth lead ing oral antidiabetic 

with 4.3% of do mes tic sales, and growth of 23%. Takeda’s Basen (voglibose) was Ja pan’s lead ing oral 

di a betic ac cord ing to IMS with 28% share of do mes tic sales, down 6% (fixed dol lar rate) over the pre vi - 

ous year. Takeda’s Actos (pioglitazone) took sec ond place with 25.1% and 22% growth while Amaryl 

(glimepiride) took third place with 13.3% (up 10%). Glufast also com petes with Astellas’ (Ja pan) Starsis 

(nateglinide), which is also mar keted by Daiichi Sankyo (Ja pan) un der the name of Fastic, which ranked 

just be hind Glufast with Fastic in sev enth place hold ing 2.9% mar ket share (down 1%) and Starsis in 

eighth po si tion with 2.4% mar ket share (up 1%). There is a cer tain amount of pos i tive in ter play be tween 

the prod ucts in that Glufast will help heighten aware ness of short and fast-act ing in su lin sectretagogues, 

ac cord ing Astellas. There is also syn ergy with Takeda’s established brands like Basen and Actos. 

Sales/An a lyst Com ment: With sales of Yen3.2 bil lion in fis cal 2007 (end ing March 2008) an a lysts at 

Mor gan Stan ley (Au gust 2008) fore cast sales of Yen12 bil lion by the year end ing March 2013. 

LANSAP/PREVPAC (lansoprazole + amoxicillin + clarithromycin) is a sin gle tri ple ther apy pack de - 

signed for the erad i ca tion of H. pylori. The prod uct, de signed to im prove com pli ance, com prises in di vid ual 

packs con tain ing all the med i ca tion with lansoprazole, Abbott’s Biaxin (clarithromycin) and amoxicillin, 

re quired for a sin gle day. In the USA, TAP mar kets the tri ple ther apy as Prevpac, and the com bi na tion 

has also been launched in a num ber of other mar kets, in clud ing the UK and France. In 1999, Takeda, 

Taisho (Ja pan) and Dainabot, Abbott’s Jap a nese jv with Dainippon (Ja pan), filed the reg i men in Ja pan, 

and it was launched in 2002 in Japan. 

Sales/An a lyst Com ment: In the year end ing Sep tem ber 2008, Prevpac be came Takeda’s 10th lead ing 

in ter na tional prod uct ac cord ing to IMS with 1% mar ket share down 1% (fixed dol lar growth rate). 

TAKEPRON/PREVACID/OGASTRO (lansoprazole), a sub sti tuted benzimidazole pro ton pump in hib i - 

tor with po tent and long-last ing antisecretory ac tiv ity, was pat ented and de vel oped by Takeda, and was 

launched in Ja pan in 1992. It was first launched in France in 1991, and is now avail able in most coun tries 

world wide via Takeda and a num ber of li cens ees. Lansoprazole is used and ap proved for a va ri ety of in di - 

ca tions in a num ber of coun tries, in clud ing gastroesophageal re flux dis ease (GERD), pep tic ul cers, 

NSAID-as so ci ated gas tric ul cers (phase III tri als on go ing in Ja pan in 2008), acid-re lated dys pep sia, 

Zollinger-Ellison syn drome, main te nance ther apy af ter ul cer heal ing, and main te nance ther apy for 

GERD. In De cem ber 2006, Takeda launched an in tra ve nous for mu la tion of lansoprazole (Takepron iv) for 

the treat ment of bleed ing as so ci ated with gastrointestinal ulcers in patients unable to take the drug 

orally. 

Prevacid of fers a va ri ety of ad min is tra tion modes: an oral sus pen sion form and an orally dis in te grat ing 

tab let. Prevacid SoluTab is a for mu la tion which dis in te grates quickly in the mouth, usu ally less than 60 

sec onds, and can be taken with or with out wa ter. In 2004 the FDA has ap proved this for mu la tion of 

lansoprazole to be given us ing an oral sy ringe or nasogastric tube. An orally dis in te grat ing tab let, 



Takepron OD, has been de vel oped and was launched in the UK and in Ja pan and ap proved in the USA in 

2002. TAP has launched a new ready-to-mix oral sus pen sion for mu la tion of Prevacid in the USA, in tended 

for use by peo ple who have dif fi culty tak ing cap sules. TAP says this is the first drug in the PPI cat e gory to 

be of fered in an oral sus pen sion form. It is avail able in 15mg and 30mg pack ets. In Jan u ary 2004, a 

smaller cap sule for mu la tion was ap proved for use in Ja pan for Ogast, Agopton, Lansox (EU). 

In 2003 the FDA ap proved a com bi na tion pack, Prevacid NapraPAC (lansoprazole de layed re lease cap - 

sules/naproxen tab lets) for use by pa tients tak ing NSAIDs for treat ment of ar thri tis who are at risk for re - 

cur rent gas tric ul cers. A tri ple ther apy pack for H. pylori erad i ca tion, con tain ing lansoprazole, amoxicillin 

and clarithromycin, is mar keted as Prepac in the USA and Lansap in Japan. 

In 2004, the US FDA ap proved Prevacid for the short-term treat ment of symp tom atic GERD and ero sive 

esophagitis in chil dren aged 12 to 17 years, ex pand ing its ap proved use in chil dren aged one to 17 years. 

Prevacid was the only PPI ap proved for use in chil dren as young as one year. 

Also in 2004, TAP re ceived US FDA ap proval for an in tra ve nous for mu la tion, Prevacid IV, for pa tients 

who are un able to take the oral for mu la tion. The prod uct is in di cated for short-term (up to seven days) 

treat ment of ero sive esophagitis of any grade se ver ity, un til pa tients are able to take oral ther apy, when 

they switch to the oral ver sion for up to six to eight weeks. The IV for mu la tion was ap proved in Ja pan in 

Oc to ber 2006 and launched in December 2006. 

Li cens ing: In May 2008, Abbott and Takeda con cluded their TAP joint ven ture and Takeda re tained the 

rights to lansoprazole. TAP Pharmaceuticals, Takeda’s US jv with Abbott, mar keted lansoprazole in the 

US, where it was launched in 1995 as Prevacid. Takeda Pharma mar kets it in Ger many, Aus tria and 

Swit zer land. Abbott also has rights in Can ada and a num ber of Latin Amer i can coun tries (where 

lansoprazole is sold as Ogastro). Roemmers (Ar gen tina) and Boehringer Ingelheim (Ger many) also 

have rights in Latin Amer ica. Almirall Prodesfarma (Spain) is the li censee for Spain. Wyeth (USA) is the li - 

censee for the UK, Den mark, Fin land, Swe den, Nor way, Aus tra lia and Pa ki stan, and uses trade names in - 

clud ing Zoton and Lanzo. Aventis (France) has rights in France, the Neth er lands, Bel gium, Af rica and 

the Mid dle East. Han Il (South Ko rea) the licensee for South Korea. 

Pat ents: The main pat ent for lansoprazole ex pires in No vem ber 2009 and this is set to be the big gest ex - 

pi ra tion of the year. Teva made at tempts to launch its ge neric lansoprazole in 2008 but court rul ings con - 

cluded Takeda’s pat ents to be en force able and Teva now plans to launch in November 2009. 

In June 2008, Barr Pharmaceuticals chal lenged the pat ents for Prevacid SoluTab af ter fil ing its ANDA to 

the FDA in No vem ber 2007, which has been ac cepted for fil ing. 

Lifecycle Man age ment: In 2009, Takeda re ported phase III tri als on go ing in Ja pan of lansoprazole for 

risk re duc tion of NSAIS-as so ci ated gas tric ul cer and risk re duc tion of low dos age as pi rin-as so ci ated 

gastric ulcer. 

TAP an nounced a deal in Jan u ary 2006 grant ing Novartis the right to de velop an OTC ver sion of Prevacid 

in the US, giv ing an op por tu nity to boost flag ging sales, hit by com pe ti tion from other ge neric PPIs, ahead 

of its loom ing 2009 pat ent ex piry. Novartis will take full re spon si bil ity for the OTC-switch pro gram, in clud - 

ing the de sign and con duct of clin i cal stud ies, reg u la tory sub mis sions to the FDA and man u fac tur ing, dis - 

tri bu tion and launch ac tiv i ties. Fi nan cial ar range ments were un dis closed. In June 2003, the UK’s Na tional 

Phar ma ceu ti cal As so ci a tion, which rep re sents com mu nity phar ma cists, said it was con cerned about an 

ap pli ca tion to the UK au thor i ties to make the PPI antiulcerant, omeprazole, an OTC ther apy. The as so ci a - 

tion said it pre ferred OTC lansoprazole in stead. Lansoprazole had been shown to be more ef fec tive when 

used for episodic treatment and appeared to have a better safety profile. 

TAP an nounced a li cens ing deal with Flamel Tech nol o gies’ (France) over the firm’s Micropump Tech nol - 

ogy, a con trolled re lease plat form for po ten tial use in the de liv ery of lansoprazole, the ac tive in gre di ent in 



Prevacid. At the time of the an nounce ment in Sep tem ber 2004, un der the deal TAP would pay costs of all 

fur ther de vel op ment, test ing, reg u la tory ap proval and mar ket ing of the new for mu la tion. Flamel also 

men tioned that it had the po ten tial to earn more than $100 mil lion of mile stones and would re ceive roy al - 

ties. The move rep re sented an at tempt by TAP to plug the hem or rhage in sales seen for Prevacid in the 

USA. 

Clin i cal Data: In 2003, the first head-to-head study of the five cur rently mar keted PPIs was pub lished in 

the Amer i can Jour nal of Gastroenterology. Nexium con trolled intragastric acid ity to a greater ex tent than 

the other four, de spite all the prod ucts shar ing the same mode of ac tion. In the ran dom ized, open-la bel 

cross over trial, pa tients took each prod uct for five days, 30 min utes af ter a stan dard ized break fast. The 

study com pared Nexium, Prevacid, Prilosec (omeprazole), Protonix (pantoprazole) and Aciphex 

(rabeprazole). 

In an open-la bel, US multicenter study, 87 ad o les cent pa tients with symp tom atic GERD were as signed to 

re ceive ei ther Prevacid 15 mg or 30 mg once daily. Most pa tients had mild or mod er ate GERD symp toms. 

Sixty-four pa tients had nonerosive GERD and were treated with Prevacid 15 mg daily for eight weeks, 

while 23 pa tients had ero sive esophagitis and were treated with Prevacid 30 mg daily for eight to twelve 

weeks. Prevacid was found to be safe and ef fec tive in treat ing pa tients with ero sive esophagitis and 

symp tom atic GERD. Of 22 pa tients with ero sive esophagitis, 95.5% were healed af ter eight weeks of 

treat ment, which is sim i lar to heal ing rates in adult studies. 

Com pe ti tion: The world PPI mar ket is ex tremely com pet i tive, with many prod ucts fight ing for a mar ket 

share. In the 12-month pe riod to the end of Sep tem ber 2008, ac cord ing to IMS, lansoprazole, sold as 

Takepron, was the world’s sec ond lead ing antiulcerant with a 14.4% mar ket share and a 3% de cline in 

dol lar growth. The num ber one prod uct in this area with 25.5% of the mar ket and 8% dol lar growth is 

AstraZeneca’s Nexium, its fol low on prod uct to Losec (omeprazole), sales of which fell by 16% and 

hold ing sixth place with 3.6% of the mar ket. Pariet (rabeprazole) took third place with 7.5% share. 

Pantozol (pantoprazole) took fourth place 6% share and sales down 2% while Wyeth/Altana’s Protonix 

(pantoprazole) took fifth place in the same pe riod with 3.8% of the mar ket, down 54% over the previous 

year. 

In 2007, the FDA cleared prilosec and Nexium of links to heart prob lems but dis closed a re view of po ten - 

tial links for hip frac tures fol low ing a pre vi ous re port from JAMA sug gest ing that long term use of pro ton 

pump in hib i tors can in crease hip frac ture risk in adults over 50. 

Fol low ing the with drawal of Merck & Co’s Vioxx in 2004, sales of heart burn drugs such as Prevacid or 

AstraZeneca’s Prilosec, in com bi na tion with OTC NSAIDS have gone up; re sults of a study re leased 2007 

sug gest that this com bi na tion is as ef fec tive as us ing a COX-2 in hib i tors for re duc ing the risk of NSAID 

gastropathy. 

Procter & Gam ble (USA) launched Prilosec OTC in the USA in 2003. In 2004, Bentley Pharmaceuticals 

(USA) was granted ap proval by the Span ish Health Min is try to mar ket a ge neric ver sion of lansoprazole in 

Spain and then an nounced a launch in France in 2007. Takeda al ready mar kets its branded ver sion in the 

coun try un der var i ous trade marks by a num ber of com pa nies in clud ing Merck & Co. 

Sales/An a lyst Com ment: In the year to March 31 2008, ac cord ing to Takeda, do mes tic sales of 

Takepron were Yen64.8 bil lion, up 11.8%. To tal global sales were up 8.2% to Yen148.7 bil lion. In the 

12-month pe riod to the end of Sep tem ber 2008, lansoprazole (Takepron) was Takeda’s lead ing in ter na - 

tional phar ma ceu ti cal prod uct, with 32.1% of cor po rate sales, down 3% (fixed dol lar rate) ac cord ing to 

IMS. Mor gan Stan ley an a lysts (Au gust 2008), fore cast peak con sol i dated sales of Yen301.1 bil lion in the 

next fis cal (end ing March 2009) and a grad ual de cline there af ter to Yen224 billion in the year to March 

2012. 



� Antineoplastics/Immunomodulating Agents 

CANFERON-A (in ter feron al pha-2a), a cytostatic and an ti vi ral (re com bi nant hu man in ter feron), was 

launched in 1986 in Ja pan. It was jointly de vel oped with Roche (Swit zer land) un der li cense from 

Genentech (USA) and is co-mar keted with Roche in Ja pan. Roche mar kets it world wide (in clud ing in Ja - 

pan) for a num ber of can cer and an ti vi ral in di ca tions as Roferon-A. Al pha-in ter feron is in di cated in Ja pan 

for ma lig nant mel a noma, re nal cell car ci noma and vi ral hep a ti tis. Sales of in ter feron prod ucts in Ja pan 

have been in de cline since a warn ing in 1994 by Ja pan’s then Min is try of Health and Wel fare that al - 

pha-interferons may cause de pres sion and ex ac er bate sui cidal ten den cies. In late 2003, the Min is try of 

Health, La bor and Wel fare in sisted that a range of side-ef fect warnings be added to the product label of 

Canferon and other interferons. 

CELEUK (celmoleukin), a re com bi nant interleukin-2 prod uct, was de vel oped in-house by Takeda. It was 

the first prod uct of its kind to be mar keted in Ja pan and was in tro duced in 1992. It is in di cated pri mar ily as 

an anticancer agent, par tic u larly for the treat ment of ma lig nant hemangioendotheliomas, and also for 

Ep stein-Barr virus infections. 

ISOVORIN (cal cium levofolinate), an in ject able methotrexate res cue in osteosarcoma and mod u la tion 

of 5-FU drug ther apy in colorectal, breast, head, and neck can cers. Isovorin re duces the side ef fects of 

methotrexate on cells lin ing the mouth and gut as well as blood cells in volved in fight ing in fec tion. 

Levofolinic acid is given by in tra ve nous in jec tion or in fu sion, or by in tra mus cu lar (into muscle) injection. 

Sales/An a lyst Com ment: Mor gan Stan ley an a lysts (Au gust 2008) fore cast sales de clin ing to Yen10.0 

bil lion by the year to March 2013. 

LEUPLIN/LUPRON (leuprorelin), a luteinizing hor mone-re leas ing hor mone (LHRH) an a logue, is in di - 

cated in the treat ment of pros tate can cer, endometriosis and uter ine fib roids. It is also in di cated in the 

treat ment of pre co cious pu berty and breast can cer in some mar kets. Leuprorelin was Takeda’s first prod - 

uct to be sold on a global ba sis. It was orig i nally launched as a daily in jec tion in the USA in 1985 by TAP, 

Takeda’s joint ven ture with Abbott which was con cluded in May 2008 with Abbott re tain ing US rights to 

this product. 

It was launched in Ja pan (as Leuplin) and is now avail able in over 60 mar kets world wide. In 2005 the Min - 

is try of Health, La bor and Wel fare added pre cau tions of pi tu itary ap o plexy and blurred vi sion to the prod - 

uct la bel. Leuprorelin was de vel oped over seas be fore be ing launched on the do mes tic mar ket be cause of 

the higher in ci dence of pros tate can cer over seas. In France and It aly leuprorelin is mar keted as 

Enantone. Takeda Pharma mar kets it in Ger many and Aus tria (as Enantone), and a pre-filled sy ringe 

im plant ver sion was launched in Ger many as Trenentone in 2003. An a lysts state that the key to the 

prod uct’s suc cess is its availability in long-acting dosage forms. 

Lupron De pot was orig i nally a monthly dos age form, slowly re leased from a “de pot” in jected into a mus - 

cle. Takeda has been de vel op ing a num ber of slow-re lease ver sions, in clud ing Lupron De pot-4, where 

pa tients only re quire an in jec tion ev ery four months and Lupron De pot-3 (once ev ery three months). A 

four monthly Leuplin SR for In jec tion Kit for pros tate can cer us ing a new microcapsule base was 

launched in Ja pan in Au gust 2002 for pros tate can cer. In Au gust 2005 Takeda an nounced that the Jap a - 

nese Min is try of Health, La bor and Wel fare has granted mar ket ing ap proval for sus tained-re lease 

leuprorelin (Leuplin SR) as an ad junct to pre vent re lapses of premenopausal breast can cer. The clear ance 

is for the 11.25mg three-month microcapsule de pot kit for mu la tion, and the 3.75mg kit, and stan dard 

foruulations are also ap proved for use in help ing post op er a tive re cur rence. A six-month de pot for mu la - 

tion suit able for pros tate can cer ther apy was ap proved in the USA in 2004 and in Eu rope in 2008 where it 

has been launched (France, Germany and Austria). 



Clin i cal Data: In 2000, re sults of a trial of Lupron in Alz hei mer’s dis ease were pre sented (go nad o tro pin 

lev els are higher in women with Alz hei mer’s). TAP was spon sor ing fur ther re search in this area. 

Li cens ing: Leuprorelin has been li censed out to Abbott for Can ada, Eu rope, Mex ico and sev eral other 

Latin Amer i can coun tries. The TAP jv mar keted it in the USA. Abbott and Takeda con cluded their TAP joint 

ven ture in May 2008 and Abbott re ceived rights to Lupron. 

In No vem ber 2003, TAP ob tained an ex clu sive li cense from Norwood Ab bey (Aus tra lia) to ex pand the in - 

di ca tions for Lupron. Norwood has been in ves ti gat ing ways in which LHRH can be used to boost T-cell 

pro duc tion by the thy mus gland, pro duc tion which nor mally de clines with pu berty. LHRH may be able to 

tem po rarily block pro duc tion of sex ste roids that are re spon si ble for this de cline. The two com pa nies will 

jointly fund R&D to as sess ap pli ca tions in fields in clud ing bone mar row trans plan ta tion, can cer and 

HIV/AIDS. TAP would have re spon si bil ity for fil ing any re sult ing sNDAs, and would pay mile stones and 

roy al ties to Norwood. In ad di tion, TAP ac quired a $2 mil lion eq uity stake in Norwood Im mu nol ogy, a 

wholly owned Norwood subsidiary based in the UK. 

Pat ents: In 1999, Takeda filed law suits against OWL Pharmaceuticals and Oakwood Lab o ra to ries (USA) 

with a US dis trict court claim ing in fringe ment of 12 pat ents re lated to its leuprorelin de pot for mu la tion. 

OWL had sub mit ted an ANDA in the US for a ge neric ver sion of Lupron De pot. The suit called for a halt to 

ac tiv i ties that in fringe Takeda’s pat ents and post pone ment of FDA ap proval un til those pat ents ex pire. 

Ac cord ing to Takeda, the pat ents will re main in effect until after 2010. 

Oakwood Lab o ra to ries (USA) has filed suit in the US Dis trict Court al leg ing that TAP and its co-own ers Ab - 

bot and Takeda have been and are in fring ing the US ‘542 pat ent by mak ing and sell ing sus tained-re lease 

leuprolide ac e tate prod ucts un der the trade name Lupron De pot. The suit fur ther al leges that TAP and its 

par ent com pa nies had knowl edge of the pat ent, which was is sued in 1989, and that the in fringe ment was 

will ful. The suit was filed by Oakwood Lab o ra to ries and the Uni ver sity of Ken tucky Re search Foun da tion, 

the pat ent owner and li cen sor of rights under the ‘542 patent to Oakwood. 

In 2003, TAP filed a suit against Atrix (now QLT, USA) and its li censee Sanofi-Synthelabo (now 

sanofi-aventis, France) al leg ing that the use of the Atrigel de liv ery sys tem in their prod uct Eligard 

(leuprolide ac e tate for in ject able sus pen sion) in fringes a Takeda and Waco US patent. 

In Sep tem ber 2007, Takeda set tled lit i ga tion amount ing to Yen37.6 mil lion re lat ing to the be reaved fam - 

ily of an em ployee who had been in volved in de vel op ing con trolled re leased for mu la tion of Leuplin. 

Lifecycle Man age ment: The FDA ap proved an IND for a trial us ing Lupron De pot to re ju ve nate the thy - 

mus gland and im prove im mune re sponse in pa tients who re ceived an autologous bone mar row trans - 

plant, us ing an ap proach de vel oped by Aus tra lia’s Norwood Im mu nol ogy and will be co-funded by the US 

Na tional Can cer In sti tute and the Na tional In sti tute of Al lergy and Infectious Disease. 

TAP, Takeda’s fully-owned US sub sid iary, an nounced in 2003 that LuproLoc be came avail able for use 

with Lupron De pot (leuprolide ac e tate for de pot sus pen sion) as the first prod uct in its class to of fer a nee - 

dle safety de vice on pre-filled sy ringes. LuproLoc, which was ap proved by the US FDA, fea tures an in no - 

va tive, in te grated safety mech a nism at tached to pre-filled sy ringes con tain ing Leupron De pot. The new 

prod uct is de signed to of fer healthcare work ers ad di tional pro tec tion from needlestick in jury, which is a 

cause of oc cu pa tional ex po sure to dis eases such as HIV, hep a ti tis B and hep a ti tis C. The FDA ap proval is 

the re sult of fil ings with both the FDA’s cen ter for Drug eval u a tion and Re search (CDER) and its Cen ter for 

De vices and Ra dio log i cal Health (CDRH). The de vice is the first prod uct to come to mar ket fea tur ing tech - 

nol o gies li censed by TAP from Spe cial ized Health Prod ucts In ter na tional (SHPI). Takeda has now de vel - 

oped a num ber of slow-re lease ver sions, in clud ing Lupron De pot-4, where pa tients only re quire an 

in jec tion ev ery four months and Lupron De pot-3 (once ev ery three months). A six-monthly in jec tion was 

awaiting approval in 2007 in Germany, Italy and France following filings in 2005. 



Norwood Ab bey (Aus tra lia) is in volved with Takeda in an ad di tional clin i cal study which will pro vide a 

greater un der stand ing of the ef fects of Lupron on the out put of new T-cells from the thy mus, as well as 

changes in other cel lu lar com po nents of the im mune sys tem. The study is be ing con ducted in con junc tion 

with TAP at a num ber of high-pro file US hos pi tals. The pro to col for this study is now be ing re viewed by the 

eth ics com mit tee at Norwood. An IND is not re quired for this trial, as it is based on the anal y sis of blood 

sam ples from pa tients al ready be ing treated with Lupron within in di ca tions al ready ap proved by the FDA. 

The study is slated to commence in the first quarter of 2005. 

A sig nif i cant new ther apy area for leuprorelin in Ja pan is endometriosis, which, with a po ten tial 70,000 

cases a year, ex ceeds the mar ket for pros tate can cer (30,000 per year). Leuprorelin has also been ap - 

proved for the treat ment of breast can cer and uter ine fib roids in Japan. 

Com pe ti tion: Lupron/Enantone ac counts for al most half (48.9%) of the To tal Cytostatic Hor mones 

ther a peu tic cat e gory. In the 12 month pe riod to the end of Sep tem ber 2008, ac cord ing to IMS, Lupron 

was num ber two in the class, with a mar ket share of 22.1%, down 5% in fixed rate dol lar terms, and 

Enantone was third with 20.6% of the mar ket, steady over the pre vi ous year. Just ahead of Lupron alone 

in terms of mar ket share was AstraZeneca’s (UK) Zoladex (goserelin), with a 26.8% mar ket share, 

steady over the pre vi ous year in fixed rate dol lar terms. The GnRH sub-seg ment of the mar ket, dom i - 

nated by Lupron and Zoladex, is worth around $2.5 billion globally. 

In April 2005, data was re leased re veal ing that pros tate can cer pa tients treated with Zoladex im me di - 

ately af ter ra di a tion ther apy live lon ger than men who wait to take the drug. Cur rently around half of 

pros tate can cer pa tients treated with ra di a tion go on to take Zoladex. These re sults could also en cour age 

ear lier use of Lupron as both drugs work in ex actly the same way and cost around the same. In May 2006, 

AstraZeneca granted Biovail rights to pro mote Zoladex to ob ste tri cians and gy ne col o gists for the treat - 

ment of endometriosis in the USA and Puerto Rico. 

In 2004, Valera Pharmaceuticals (USA) re ceived FDA mar ket ing ap proval for the firm’s long-act ing 

(12-month ad min is tra tion) im plant Vantas (histrelin), a syn thetic nonapeptide ag o nist of luteinizing hor - 

mone-re leas ing hor mone (LHRH). LHRH agonists have rap idly be come a main stay in treat ing lo cally ad - 

vanced and met a static pros tate can cer with the US mar ket, which could af fect the shorter du ra tion 

Leupron Depot sales. 

Sales/An a lyst Com ment: In the year to March 31 2008, ac cord ing to Takeda, do mes tic sales of 

Leuplin were Yen66.4 bil lion, up 3.3%, while to tal global sales reached Yen124.0 bil lion (down 2.7%). In 

the 12-month pe riod to the end of Sep tem ber 2008, ac cord ing to IMS, Enantone was Takeda’s num ber 

four in ter na tional phar ma ceu ti cal prod uct, gen er at ing 6.3% of cor po rate sales, up 1% over the pre vi ous 

year in fixed rate dol lar terms. Mor gan Stan ley an a lysts (Au gust 2008) fore cast Leuprin to tal sales fall ing 

to Yen112.5 billion by the year to March 2013. 

MYLOTARG (gemtuzumab ozogamicin) is a hu man ized monoclonal an ti body, linked to calicheamicin, 

which has been de vel oped by Wyeth in col lab o ra tion with Celltech Group (now part of UCB, Bel gium) and 

was first launched by Wyeth in the USA in 2000 for the treat ment of acute myeloid leu ke mia. Wyeth KK 

(Ja pan), gained ap proval for Mylotarg in Japan in 2005. 

VELCADE (bortezomib), a small mol e cule protesome in hib i tor, was launched in the USA by Mil len nium 

(now part of Takeda) in 2003 for the treat ment of mul ti ple myeloma (MM) in pa tients who have re ceived 

at least two prior ther a pies and have dem on strated dis ease pro gres sion since the last ther apy. Velcade is 

ad min is tered as an in jec tion. Li censee John son & John son from 2004 has launched it in many ex-US mar - 

kets and in Sep tem ber 2008, J&J re ported that Velcade has been ap proved as a sec ond-line ther apy for 

MM in 87 coun tries world wide. In Ja pan, Velcade was ap proved in Sep tem ber 2006 on the con di tion that 

all-pa tient post-mar ket ing sur veil lance is con ducted, a guide book for proper use is dis trib uted and that 

the pack age in sert con tains strong warn ings. Data from clin i cal tri als and ADR re ports from phy si cians 



who have used bortezomib in pa tients who im ported the drug for their own use have shown higher in ci - 

dence of lung dis or ders amongst Japanese patients than in non-Japanese patients. 

In June 2008, Velcade was ap proved for first-line use in MM in the USA: pre vi ously it had re ceived ap - 

proval for sec ond-line use in the USA. The phase III VISTA (VELCADE as Ini tial Stan dard Ther apy in MM: 

As sess ment with melphalan and prednisolone) trial to test Velcade in com bi na tion with melphalan and 

prednisolone in pa tients with newly-di ag nosed MM who are not trans plant can di dates was stopped early 

in Sep tem ber 2007 af ter in terim find ings showed that there was sig nif i cant ad van tage for newly di ag - 

nosed pa tients. A fil ing for first-line use in MM was sub mit ted in the EU in De cem ber 2007 and this was 

rec om mended for ap proval in July 2008. In Sep tem ber 2008, full ap proval was re ceived for use as a 

first-line ther apy for MM in com bi na tion with melphelan and pred ni sone. Ap proval for first-line use was 

also received in Canada in September 2008. 

The US Na tional Com pre hen sive Can cer Net work (NCCN) up dated its MM Guide lines in Oc to ber 2007 to 

in clude Velcade in com bi na tion with J&J’s Doxil (pegylated liposomal doxorubicin) as a cat e gory 1 rec - 

om men da tion for pa tients with re lapsed/re frac tory MM in the fol low ing clin i cal sit u a tions: pa tients with 

pro gres sive dis ease fol low ing allogenic or autologous stem cell trans plant (SCT); pa tients with pri mary 

pro gres sive dis ease fol low ing ini tial autologous or allogenic SCT; and non trans plant can di dates with pro - 

gres sive or re laps ing dis ease af ter ini tial in duc tion ther apy. This fol lowed the May 2007 FDA ap proval of 

Velcade plus Doxil in combination for the treatment of relapsed or refractory MM. 

In Oc to ber 2007, the FDA ap proved an ad di tional in di ca tion for Velcade for use in pa tients with im paired 

kid ney function. 

Li cens ing: In 2003, Ortho Biotech and Janssen Cilag gained rights to Velcade out side the USA from Mil - 

len nium (now part of Takeda, Ja pan). The two com pa nies also agreed to col lab o rate on the fur ther de vel - 

op ment of Velcade worldwide. 

Clin i cal Data: At the 49th An nual Meet ing of the Amer i can So ci ety of He ma tol ogy, held in At lanta in De - 

cem ber 2007, Mil len nium pre sented data from the VISTA study, its piv otal 682-pa tient trial for dem on - 

strat ing the ef fec tive ness of Velcade as a first-line ther apy for mul ti ple myeloma. Com plete re mis sion 

rates of 30-35% were seen with a com bi na tion of Velcade, melphalan and pred ni sone (VcMP), com pared 

with 4-5% seen with the stan dard reg i men of melphalan and pred ni sone (MP) alone. The me dian du ra - 

tion of re sponse was 24 months for VcMP, ver sus 13 months with MP, while time to dis ease pro gres sion 

was 24 months against 17 months. VcMP dem on strated sta tis ti cal sig nif i cance in over all sur vival, with a 

40% re duc tion in the risk of death, and me dian sur vival was not reached at 16 months. Dis con tinu a tion 

due to ad verse events was low, and sim i lar in both arms. Also at the ASH meet ing, re sults from a 

French-led phase III trial in volv ing 482 pa tients re ceiv ing ini tial treat ment for MM pre- and post-trans - 

plan ta tion were re leased. It com pared Velcade and dexa meth a sone (VcD) with vincristine, adriamycin 

and dexa meth a sone (VAD). As in duc tion ther apy, VcD led to a com plete re mis sion rate of 21%, com - 

pared with 8% for VAD. Af ter stem cell trans plan ta tion, 41% of VcD pa tients achieved remission, versus 

29% of those given VAD, saving the number of second transplantations required. 

At the 43rd An nual Meet ing of the Amer i can So ci ety of Clin i cal On col ogy, held in Chi cago in June 2007, 

data were pre sented from the phase II To tal Ther apy 3 study, which used Velcade in a reg i men called 

VTD-PACE, also con tain ing tha lid o mide, dexa meth a sone, cisplatin, adriamycin, cyclophosphamide and 

etoposide. Two cy cles were given to 303 pa tients be fore and af ter stem cell trans plan ta tion. Lon ger treat - 

ment was pro vided with Velcade, tha lid o mide and dexa meth a sone, and then tha lid o mide and dexa meth - 

a sone. The re sults were com pared with those from TT2, which in volved 323 pa tients and omit ted 

Velcade. In TT3 a com plete re sponse rate of 84% was seen, up from 68% in TT2, and fewer patients 

experienced severe adverse effects. 



In June 2007, at the 11th In ter na tional Myeloma Work shop held in Kos, Greece, study re sults re leased 

sug gested that Velcade helped with some of the com pli ca tions of MM, in clud ing bone de gen er a tion and 

re nal impairment. 

Lifecycle Man age ment: Takeda re ported that in 2009 eval u a tion in follicular NHL was un der way in the 

US (phase III) along with phase II tri als in other tumors. 

Clin i cal tri als are on go ing (alone and in com bi na tion) for a range of solid tu mors and hematologic can cers, 

such as re frac tory man tle cell lym phoma, low grade lymphoproliferative dis or ders, NHL, and chronic 

lymphocytic leu ke mia. In June 2008 Ger man re search ers re ported that Velcade may also be ef fec tive in 

the chronic au to im mune dis ease lupus. Velcade acts by in hib it ing the cell growth sig nal ing path way, in - 

duc ing apoptosis (pro grammed cell death) and pos si bly in hib it ing pro duc tion of cel lu lar ad he sion mol e - 

cules. When com bined with stan dard chemotherapeutics, it has the po ten tial to cause the death of 

can cer ous cells. Re sults pre sented at ASCO in June 2006 dem on strated the po ten tial of Velcade across 

solid and he ma to log i cal can cers, in clud ing: high sin gle-agent re sponse rates in newly di ag nosed MM pa - 

tients; and im proved sur vival in front-line ad vanced lung can cer. Data pre sented at ASCO 2007 showed 

that Velcade also has potential in a broader NHL population including newly diagnosed NHL patients. 

Velcade is cur rently be ing in ves ti gated as a monotherapy in ad di tional in di ca tions and in com bi na tion 

with sev eral other chemotherapeutic agents by Mil len nium and J&J as well as by other com pa nies. To 

date the fol low ing tri als have been reported: 

Velcade plus Alimta (pemetrexed): In March 2006, Mil len nium and J&J Phar ma ceu ti cal Re search and 

De vel op ment ini ti ated a phase II trial to eval u ate Velcade in com bi na tion with Lilly’s Alimta 

(pemetrexed) in pa tients with lo cally ad vanced or met a static non-small cell lung can cer (NSCLC) who 

have failed pre vi ous che mo ther apy reg i mens. The ran dom ized, open-la bel, three-arm trial will en roll 135 

pa tients at mul ti ple cen ters, who will re ceive 1.6mg/m2 bortezomib weekly in com bi na tion with 

pemetrexed, or ei ther agent alone. The pri mary end point is ob jec tive re sponse rate, as mea sured by Re - 

sponse Eval u a tion Criteria in Solid Tumors (RECIST) criteria. 

Velcade plus Roche’s Tarceva (erlotinib): Mil len nium and J&J are con duct ing a phase II trial to eval u ate 

bortezomib in com bi na tion with erlotinib in pa tients with ad vanced or met a static NSCLC, Velcade plus 

Roche’s Rituxan (rituximab): In April 2006, Mil len nium and J&J ini ti ated a phase III clin i cal trial of 

Velcade in com bi na tion with rituximab in pa tients with re lapsed or re frac tory follicular lym phoma, a sub - 

type of NHL. This study builds on clin i cal data ob served in pre vi ous tri als of Velcade that showed high ob - 

jec tive re sponse rates and a fa vor able safety pro file across a va ri ety of lym pho mas. 670 pa tients are 

expected to be enrolled in the trial. 

Velcade plus HGS-ETR1 (mapatumumab): In July 2006, Hu man Ge nome Sci ences (USA) be gan dos ing 

pa tients with ad vanced MM (re lapsed or re frac tory) in a ran dom ized phase II clin i cal trial of HGS-ETR1 

(mapatumumab) in com bi na tion with Velcade. The pri mary ob jec tive of the study is to eval u ate dis ease 

re sponse to HGS-ETR1 in com bi na tion with bortezomib, ver sus bortezomib alone. Velcade in a four drug 

ther apy: In Au gust 2007, Mil len nium ini ti ated a ran dom ized phase II trial (EVO LU TION) to eval u ate a 

four-drug ther apy in ap prox i mately 100 pa tients with newly di ag nosed MM at mul ti ple sites in the USA. 

The trial will as sess the ef fi cacy of a com bined ther apy con sist ing of Velcade for in jec tion, Celgene’s 

Revlimid (lenalidomide) and dexa meth a sone; the in cre men tal ben e fit of the ad di tion of 

cyclophosphamide to this reg i men will also be ex am ined. The pri mary ob jec tive of this trial is to achieve 

com plete re sponse and very good par tial re sponse rates. Sec ond ary end points will include duration of 

response, overall survival, safety, and tolerability. 

Velcade plus Wyeth’s Torisel (temsirolimus): A multi-cen ter phase I/II clin i cal pro gram to in ves ti gate 

the com bi na tion of temsirolimus and Velcade for the treat ment of re lapsed or re frac tory MM be gan in the 

USA in Sep tem ber 2007. 



Velcade in a trans plant set ting: Phase III ran dom ized study of vincristine, adriamycin, dexa meth a sone 

ver sus Velcade, adriamycin and dexa meth a sone as an in duc tion ther apy and Velcade main te nance in the 

trans plant setting. 

Velcade plus SGN 40: In June 2008 Se at tle Ge net ics/Genentech (USA) ini ti ated a phase Ib trial of SGN 

40 plus Velcade in pa tients with re lapsed or re frac tory MM. 

In Sep tem ber 2008, Mil len nium re ported that there are also a num ber of on go ing phase I and II tri als 

with Velcade as a sin gle agent or in com bi na tion with other chemotherapeutic agents as a po ten tial treat - 

ment for hematologic ma lig nan cies in clud ing non-Hodg kin’s lym phoma and Waldenstrom’s 

macroglobulinemia, and var i ous solid tu mors in clud ing lung, breast, pros tate and ovarian cancers. 

In Au gust 2006, the FDA granted Mil len nium a pri or ity re view des ig na tion for Velcade for the treat ment of 

re lapsed man tle cell lym phoma, an ag gres sive, in cur able sub type of NHL, for which there is cur rently no 

standard of care. 

In terim anal y sis of a phase III, ran dom ized, open-la bel study of 646 pa tients with re lapsed or re frac tory 

MM showed that the com bi na tion of J&J’s Doxil (doxorubicin) and Velcade pro vided a nearly three month 

im prove ment in time to dis ease pro gres sion, ver sus Velcade alone. The data was pre sented in De cem ber 

2006 at the meet ing of the Amer i can So ci ety of He ma tol ogy. The study re sults dem on strate that pa tients 

who re ceived Doxil/Velcade had 45% less risk of their dis ease pro gress ing and a sta tis ti cally sig nif i cant 

im prove ment in me dian time to dis ease pro gres sion. The pat terns of ad verse events were con sis tent with 

the known tox ic i ties of Doxil and Velcade. There was an in crease in clin i cally rel e vant treat ment-re lated 

ad verse events as so ci ated with the com bi na tion of Doxil plus Velcade, mostly due to in creased 

hematologic ad verse events such as ane mia (low red blood cell count), neutropenia (low white blood cell 

count), thrombocytopenia (low platelet count), and gas tro in tes ti nal ad verse events (such as con sti pa - 

tion, di ar rhea, nau sea and vom it ing). The in ci dences of se ri ous ad verse events (36% and 31% for the 

Doxil/Velcade and Velcade groups, re spec tively) and ad verse events with out come of death (4% and 

3%, re spec tively) tended to be sim i lar be tween the two treat ment groups. The in ci dences of 

thromboembolic events (blood clots) were 1% for both the com bi na tion and for Velcade monotherapy. 

16% of pa tients ran dom ized to the com bi na tion ex pe ri enced hand-foot syn drome, whereas none of the 

pa tients re ceiv ing Velcade monotherapy ex pe ri enced this side ef fect. In Jan u ary 2007, J&J filed an sNDA 

for Doxil as com bi na tion ther apy with Velcade for injection to treat patients with MM who have received at 

least one prior therapy. This was approved in May 2007. 

In June 2007, Mil len nium re ported pos i tive data for Velcade for MM pa tients who had re ceived at least 

one prior ther apy. Data in cluded re sults from a phase II trial for sub cu ta ne ous ad min is tra tion of Velcade, 

which is an op tion be ing eval u ated by Millennium and J&J. 

Com pe ti tion: Celgene’s Thalomid (tha lid o mide) is re ported to be the most widely-pre scribed drug for 

MM, but is known to cause se ri ous birth de fects if used by women of child bear ing age. Tha lid o mide is an 

old drug (first in tro duced in the 1950s) and is used off la bel for a va ri ety of dis eases. Celgene is re ported 

to be seek ing for mal ap proval for use in MM, but the FDA has asked for up dated safety in for ma tion be fore 

al low ing the drug to be mar keted for treat ing newly-di ag nosed MM. How ever, in March 2006, it was re - 

ported that tha lid o mide failed in a study to pro long the lives of pa tients with MM. In June 2006, up dated 

clin i cal data from an on go ing multi-cen tered, ran dom ized, pla cebo-con trolled phase III study of oral 

com bi na tion ther apy tha lid o mide plus dexa meth a sone ver sus dexa meth a sone alone as in duc tion ther - 

apy for pre vi ously un treated MM sug gested that the com bi na tion of tha lid o mide plus dexa meth a sone led 

to a sta tis ti cally sig nif i cant im prove ment in median time to disease progression; this was the primary 

endpoint of this trial. 

Celgene has now de vel oped a suc ces sor drug, the immunomodulator Revlimid (lenalidomide) for the 

treat ment of mul ti ple myeloma and MDS. Revlimid in com bi na tion with dexa meth a sone was ap proved 



for the treat ment of MM by the US FDA in June 2006 and by the Eu ro pean Com mis sion in June 2007, by 

the Aus tra lian Ther a peu tic Goods Ad min is tra tion in Jan u ary 2008, and in Can ada in Oc to ber 2008. In 

June 2007 Celgene launched the agent in the UK and Ger many for the treat ment of MM in pa tients who 

have re ceived at least one prior ther apy. In June 2008 pos i tive data from phase III tri als of Revlimid plus 

dexa meth a sone in newly di ag nosed MM pa tients was re ported at ASCO. The two stud ies re ported a sur - 

vival advantage and improved complete response rates. 

In Feb ru ary 2006, Celgene launched Revlimid in the USA for the treat ment of trans fu sion-de pend ent 

ane mia due to low or in ter me di ate-1-risk myelodysplastic syn dromes (MDS) as so ci ated with a de le tion 

5q cytogenetic ab nor mal ity with or with out other cytogenetic ab nor mal i ties. An MAA was sub mit ted to 

the EMEA in Au gust 2005 seek ing ap proval of the drug for the treat ment of trans fu sion-de pend ent ane - 

mia due to low- or in ter me di ate-1-risk MDS as so ci ated with a de le tion 5q cytogenetic ab nor mal ity with or 

with out ad di tional cytogenetic ab nor mal i ties; the EMEA ac cepted the MAA for re view in Oc to ber 2005. 

How ever, in Jan u ary 2008, the EMEA is sued a negative opinion, and in June 2008 Celgene withdrew the 

MAA. 

In June 2008, Keryx Biopharmaceuticals (USA) re ported re sults from a multicenter, open-la bel US phase 

II trial of its drug perifosine (KRX 0401) in pa tients with MM. The trial as sessed the safety and ef fi cacy of 

perifosine alone and in com bi na tion with dexa meth a sone in pa tients with re lapsed and/or re frac tory MM. 

Other drugs in de vel op ment for mul ti ple myeloma in clude carfilzomib from Proteolix (USA) which in July 

2008 was in a phase II trial in pa tients with re lapsed MM in com bi na tion with lenalidomide and dexa meth - 

a sone and was granted or phan drug des ig na tion in April 2008. 

In the 12-month pe riod to the end of June 2008, Velcade was num ber eight in the ‘All Other 

Antineoplastics’ class with a 3.3% mar ket share and 36% fixed rate dol lar growth. This class was led by 

MabThera/Rituxan (rituximab) with an 18% mar ket share and 14% dol lar growth, fol lowed by Roche’s 

breast can cer drug Herceptin (trastuzumab) with a 15.6% mar ket share and 14% dol lar growth. 

Revlimid, Velcade’s di rect com pet i tor, is clas si fied as ‘To tal Immunosuppressive Agents’ in which it has a 

mar ket share of 3.9% with 388% fixed dollar growth. 

Sales/An a lyst Com ment: Ac cord ing to IMS, Velcade was Takeda’s eighth lead ing in ter na tional prod - 

uct in the year end ing Sep tem ber 2008 with 2.5% of cor po rate sales, up 40% over the pre vi ous year 

(fixed-dol lar growth). Velcade brought Takeda sales of Yen30.3 bil lion in fis cal 2007 (end ing March 

2008). An a lysts at Mor gan Stan ley (Au gust 2008) fore cast sales of Yen76.7 bil lion by the year end ing 

March 2013 for Takeda. 

� Cardiovascular System Agents 

ADECUT/CUPRESSIN (delapril), an ACE in hib i tor, was launched in Ja pan in 1989. It has since been 

launched in sev eral mar kets in clud ing South Ko rea, Thai land, In do ne sia and the Phil ip pines. It is in di - 

cated in the treat ment of es sen tial and re nal hypertension. 

Li cens ing: Delapril was li censed-out to Chiesi (It aly) for Eu rope and Brazil and launched by Chiesi in It - 

aly in 1995. 

Lifecycle Man age ment: Li censee Chiesi has de vel oped a com bi na tion of delapril and the cal cium an - 

tag o nist manidipine, with the trade name Vi vace. It was launched in Aus tria in Sep tem ber 2005 and in 

Ger many in Feb ru ary 2006. In March 2006, it was launched in Brazil as Hipertil. Delapril, and the cal - 

cium an tag o nist, manidipine were orig i nally de vel oped by Takeda, and li censed by Chiesi for Eu rope and 

Brazil. Takeda does not ap pear to be de vel op ing this com bi na tion product in Japan, however. 



Chiesi has also in de pend ently de vel oped Delapride (delapril/indapamide), a com bi na tion of delapril and 

the di uretic indapamide. Delapride was launched in It aly for the treat ment of hy per ten sion in 1997. The 

com bi na tion acts syn er gis ti cally and is in di cated in pa tients with mod er ate to se vere hy per ten sion. It was 

launched in Tu ni sia in 2005 and in Austria in March 2006. 

ADVICOR (ni a cin + lovastatin ex tended re lease) is ap proved in the USA for the treat ment of mul ti ple 

lipid dis or ders. 

Li cens ing: Takeda (through TPNA) signed an agree ment with Kos (now Abbott, USA) in 2003, to co-pro - 

mote the prod uct from Jan u ary 2004. An iden ti cal agree ment was signed for Kos’s other cho les terol 

prod uct, Niaspan (ni a cin). Both agree ments are due to last three years, but can be ex tended. If the com - 

pa nies do not re new the part ner ship, Takeda will be el i gi ble to re ceive de clin ing tail pay ments for a pe riod 

of three years fol low ing 2006. Un der the agree ment, TPNA’s 1,000-strong US sales force will co-pro mote 

the prod ucts and Takeda will re ceive an un dis closed per cent age of net sales for Kos’s (now Abbott’s) cur - 

rent cho les terol franchise above a specific baseline level. 

BLOPRESS (candesartan cilexetil), a long-act ing an gio ten sin II an tag o nist (AIIA) for the treat ment of 

hy per ten sion, de vel oped by Takeda, was first launched in Ger many in 1997, by Takeda Pharma, which 

co-mar kets it with AstraZeneca (UK). It is mainly sold over seas by li censee AstraZeneca, and is now 

avail able in over 70 coun tries. In 1999, Takeda launched Blopress in Ja pan where ap proval in heart fail - 

ure is still awaited fol low ing a filing in 2002. 

In 2005, a safety warn ing was added to the la bel of four AIIAs, in clud ing Blopress, for risk of low blood 

sugar lev els fol low ing sev eral re ports in pa tients tak ing the prod ucts. In 2003, use pre cau tions for 

Blopress in Ja pan have been mod i fied to in clude state ments on the pos si bil ity of in ter sti tial pneu mo nia, as 

well as fe ver, cough, and breath ing dif fi cul ties, and treat ment should be dis con tin ued should these symp - 

toms ap pear, says a Min is try of Health, Labor and Welfare’s ADR bulletin. 

In 2004, candesartan was ap proved in the EU, ex cept France and ex panded mem ber states, for chronic 

heart fail ure (CHF). This al lows its use both for heart fail ure pa tients in ad di tion to stan dard back ground 

ther apy in clud ing ACE-in hib i tors, and in pa tients in tol er ant of ACE-in hib i tor ther apy. In 2004, 

AstraZeneca and Takeda com pleted the EU’s mu tual rec og ni tion pro ce dure for ap proval of a 32 mg tab let 

of candesartan. Candesartan is al ready avail able in 2, 4, 8, and 16 mg doses and the new strength will be 

launched on a coun try-by-coun try ba sis. The two new pa tient groups were clearly shown to ben e fit from 

the prod uct in the CHARM-Added and CHARM-Al ter na tive stud ies re ported in the 2003 Eu ro pean So ci ety 

of Car di ol ogy meet ing. The new la bel will not, how ever, al low candesartan cilexetil’s use in heart fail ure 

pa tients with pre served left ven tric u lar func tion. These ac count for around half of all CHF pa tients and al - 

though they have better out comes than those with small ejec tion frac tions, they still ex pe ri ence high 

rates of mor tal ity and hos pi tal iza tion for heart fail ure. The EU ap proval does not cover France, where as 

for the ini tial hy per ten sion in di ca tion, a na tional pro ce dure is being pursued. Also, the drug does not get 

approval for the expanded member states. 

The FDA granted ap proval of Atacand for heart fail ure in 2005 in the US in pa tients with left ven tric u lar 

sys tolic dys func tion, to re duce car dio vas cu lar death and to re duce heart fail ure hos pi tal iza tions. Atacand 

had pre vi ously only been avail able in the US for hy per ten sion, and this was based on the CHARM-Al ter na - 

tive study re sults. This was fol lowed by FDA ap proval in May 2005 of Atacand in com bi na tion with an ACE 

in hib i tor to re duce car dio vas cu lar death and heart fail ure hos pi tal iza tions in heart fail ure pa tients with left 

ven tric u lar sys tolic dys func tion (with ejec tion frac tion be low 40%). This lat est ap proval was largely based 

on re sults of the CHARM-Added study. Data from the third CHARM-Pre served study in the pop u la tion with 

ejec tion frac tion above 40% only showed a trend to wards ben e fit for the pri mary end point, de spite a sig - 

nif i cant reduction in the secondary endpoint of heart failure hospitalization. 



Li cens ing: Candesartan cilexetil has been li censed out to the fol low ing: AstraZeneca for ex clu sive mar - 

ket ing in Bel gium, Den mark, Fin land, the Neth er lands, Nor way, New Zea land, Aus tra lia, and South Af - 

rica, and co-mar ket ing in the rest of the world out side Ja pan; Teva (Is rael) for Is rael; Orion (Fin land) for 

Ire land; Almirall Prodesfarma (Spain) for Spain; and Abbott (USA) for co-mar ket ing in Mex ico, Brazil, and 

Ar gen tina with AstraZeneca, and in Chile with Saval. In Ger many, Swit zer land and Aus tria, it is mar keted 

as Blopress by Takeda Pharma and by AstraZeneca as Atacand (candesartan cilexetil). 

Clin i cal Data: In Oc to ber 2006 a head-to-head com par i son with Pfizer’s Norvasc (amlodipine besylate) 

found com pa ra ble re duc tions in car dio vas cu lar events in high-risk hy per ten sive pa tients as well as sev - 

eral ad di tional sec ond ary ben e fits for candesartan such as a sig nif i cant 36% re duc tion in the new on set of 

di a be tes, par tic u larly in obese pa tients and also in duced. The find ings were pre sented at the So ci ety of 

Hy per ten sion meet ing in Ja pan and could sup port the wider use of candesartan in pa tients with met a bolic 

syn drome, char ac ter ized by mul ti ple risk fac tors such as obe sity and hy per ten sion. The study, CASE-J 

(candesartan antihypertensive sur vival eval u a tion in Ja pan) en rolled 4,728 hy per ten sive Jap a nese pa - 

tients. These find ings are of par tic u lar im por tance to Takeda in Ja pan where al most all obese pa tients 

were also hy per ten sive, un like in the US and Eu rope and this could give Takeda an edge with Blopress 

over Norvasc, al though the com pet i tor has al ready dem on strated ben e fits such as car diac event risk 

reduction, cardiovascular benefits and also in combination with ACE inhibitor therapy. 

In 2006, AstraZeneca re ported re sults of the ‘TRO PHY’ study re veal ing that pa tients with 

‘prehypertension’ (des ig nated as 140/90) were 15.6% less likely to de velop hy per ten sion than placebo. 

Fur ther data from the CHARM pro gram have been re ported in 2004, and data from a me dian fol low-up of 

3.1 years in the CHARM pro gram have been re ported in July 2005. The CHARM pro gram en rolled 7601 

pa tients with heart fail ure. At a me dian fol low-up of 3.1 years, the com pos ite end point of new di a be tes di - 

ag no sis or death oc curred in 25.2% of candesartan cilexetil-treated pa tients, com pared with 28.6% of 

pla cebo-treated pa tients. A con sis tent re duc tion in the rate of new on set of di a be tes was seen in all 

groups of pa tients with heart fail ure symp toms of vary ing severities, and tak ing dif fer ent con com i tant 

drugs, such as beta-blockers or di uret ics. The mag ni tude of this ef fect ap peared to be smaller in pa tients 

tak ing con com i tant ACE in hib i tors. A 29% re duc tion in the rel a tive risk of new on set di a be tes was seen 

across all pa tients en rolled in the CHARM pro gram, except for those receiving a concomitant ACE inhibitor 

therapy. 

In 2003, sev eral sets of re sults from the CHARM (Candesartan in Heart fail ure As sess ment of Re duc tion in 

mor tal ity and Mor bid ity) trial were re ported. In 2001, AstraZeneca com pleted re cruit ment into the 

CHARM trial, which in volved 7,601 par tic i pants, at more than 610 sites in 26 coun tries. Its aim was to see 

whether candesartan im proves sur vival in a broad spec trum of pa tients with symp tom atic heart fail ure, 

al ready dem on strated with com pet i tor Diovan (valsartan) from Novartis (Swit zer land). The end points 

used in the CHARM trial in cluded mor tal ity and hos pi tal iza tions at trib uted to heart fail ure, as well as 

all-cause mor tal ity. This se lec tion of end points, along with the in clu sion of many pa tients with pre served 

left ven tric u lar func tion, led to the re sults re ceiv ing a mixed re cep tion. Over all, the trial suc cess fully dem - 

on strated that candesartan re duced the risk of car dio vas cu lar death or hos pi tal iza tion in pa tients with 

chronic heart fail ure and di min ished left ven tric u lar func tion. These re sults were in de pend ent of whether 

pa tients were or were not tak ing an ACE in hib i tor con cur rently. Nev er the less, within the en tire dataset, 

im prove ment in all-cause mor tal ity was of bor der line sig nif i cance and it re mained un clear whether the 

im prove ments seen rep re sented a qual i ta tive ef fect or merely the con se quence of in creased sup pres sion 

of the renin-an gio ten sin sys tem. AstraZeneca announced in 2003 that, as predicted, it planned a filing for 

heart failure in late 2003 or early 2004 worldwide. 

AstraZeneca re ported re sults from a Phase II AC CESS (Acute Candesartan Cilexetil Eval u a tion in Stroke 

Sur vi vors) trial of Atacand in July 2003. The agent was well tol er ated and re duced the num ber of vas cu lar 

events by 45% dur ing 12 months fol low ing acute stroke in pa tients with high blood pres sure. Cu mu la tive 

mor tal ity in the 12 months was 2.9% from candesartan cilexetil-treated pa tients com pared with pla - 



cebo-treated pa tients at 7.2%. An other sig nif i cant find ing was that as long as the drug was given at least 

three days af ter a stroke, pa tients’ car dio vas cu lar mor bid ity and mor tal ity were im proved. No car dio vas - 

cu lar or cerebrovascular events oc curred as a re sult of low blood pres sure after treatment with 

candesartan cilexetil. 

Re sults of the SCOPE study in volv ing 4,964 el derly pa tients with high sys tolic blood pres sure were re - 

ported at the Amer i can Heart As so ci a tion meet ing in No vem ber 2003. Candesartan dra mat i cally re duced 

the risk of fa tal and non-fa tal strokes ver sus pla cebo, de spite both groups of pa tients main tain ing sim i lar 

val ues for systolic blood pressure. 

AstraZeneca an nounced in July 2004 that it had sub mit ted a sup ple men tal NDA to the US FDA for ap - 

proval of Atacand for the treat ment of chronic heart fail ure (CHF). The study re search ers con cluded that 

candesartan should be con sid ered in all chronic heart fail ure pa tients. How ever, other ex perts at the 

meet ing were not as cer tain that the find ings could be ap plied so broadly, point ing to less con vinc ing data 

for pa tients with pre served left ven tric u lar func tion. Ear lier in April 2004, Takeda Eu rope R&D Cen ter in 

Lon don filed a Eu ro pean ap proval ap pli ca tion for Blopress for CHF (the UK will act as ref er ence mem ber 

state). The mu tual rec og ni tion vari a tion pro ce dure for the prod uct cov ers Aus tria, Ger many, It aly, Ire - 

land, Por tu gal, Spain, and the UK, where the Jap a nese firm has mar ket ing rights. Sep a rate sub mis sions 

will be made soon in France and Swit zer land. The filings were based on the results of the CHARM 

program. 

In Au gust 2004, data pre sented at the Eu ro pean So ci ety of Car di ol ogy (ESC) Con gress re in forced the 

ben e fits of candesartan cilexetil in pa tients with CHF and re duced left ven tric u lar ejec tion frac tion (LVEF). 

The data dem on strated a sig nif i cant re duc tion in deaths and CHF hos pi tal ad mis sions in fa vor of the com - 

pound, add ing fur ther sup port to the July 2004 an nounce ment. A pre-spec i fied anal y sis in the group of 

CHARM pa tients with heart fail ure and re duced LVEF, the higher risk pop u la tion most fre quently stud ied 

in pre vi ous heart fail ure clin i cal tri als, dem on strated a 12% rel a tive risk re duc tion in all cause deaths and 

a 16% rel a tive risk re duc tion in car dio vas cu lar deaths when candesartan was added to stan dard treat - 

ment. The ef fect of treat ment with candesartan was sim i lar ir re spec tive of background treatment with 

ACE-inhibitors, beta-blockers, or spironolactone. 

Lifecycle Man age ment: In Au gust 2008, Takeda re vealed that it is de vel op ing a fixed-dose com bi na - 

tion of candesartan with the cal cium an tag o nist amlodipine in Ja pan, un der go ing phase III development. 

A com bi na tion prod uct with a di uretic (Blopress Comp/Blopress R) has been launched in a num ber of 

mar kets (see sep a rate drug re cord), and Takeda is now de vel op ing the drug for sev eral new indications. 

In 2000, Takeda and AstraZeneca launched the DI RECT (DI a betic REtinopathy Candesartan Trial) pro - 

gram, which com prises three clin i cal tri als within one pro gram is ex am in ing whether candesartan can 

pre vent the on set and pro gres sion of di a betic retinopathy, a com pli ca tion of di a be tes that can lead to 

blind ness. There is cur rently no spe cific treat ment for di a betic retinopathy, though glycemic and blood 

pres sure con trol can help. The trial has com pleted the ran dom iza tion of 5238 pa tients with type I and II 

di a be tes in 30 coun tries, to re ceive ei ther 32 mg candesartan cilexetil or pla cebo and AstraZeneca re - 

ported base line data for 5231 di a betic pa tients en rolled in this trial in May 2005. Full re sults of the three 

dou ble-blind stud ies in volv ing 5,213 pa tients, ran dom ized to re ceive 32mg of candesartan or pla cebo for 

at least four years were re ported in Sep tem ber 2008 and pub lished in The Lan cet. Candesartan re duced 

the in ci dence of di a betic retinopathy by 18% com pared with pla cebo. In the type I di a bet ics with 

retinopathy there was no dif fer ence in pro gres sion be tween the two groups while candesartan re duced 

the pro gres sion of retinopathy in type 2 di a bet ics by 13% com pared with pla cebo. As a con se quence of 

the re sults, Takeda de cided not to pursue this indication in prevention of the onset and progression of 

diabetic retinopathy. 



In 2001, AstraZeneca an nounced the ini ti a tion of a clin i cal study ex am in ing Atacand as add-on ther apy 

with the ACE in hib i tor Zestril (lisinopril) for low er ing blood pres sure. In volv ing 1,000 hy per ten sive pa - 

tients from 150 sites across the USA, the study was de signed to re spond to the re sults of re cent health 

sur veys sug gest ing that only 27% of hy per ten sive pa tients have their blood pres sure ad e quately con - 

trolled at the de sired blood pressure target of 140/90 mmHg. 

Com pe ti tion: Blopress was the third best sell ing AIIA in its class (C9C, To tal An gio ten sin II An tag o nists, 

Plain) in the 12 months to Sep tem ber 2008, with 11.4% mar ket share and 6% dol lar growth, ac cord ing 

to IMS. Novartis’ (Swit zer land) Diovan (valsartan) is mar ket leader with a 26.3% mar ket share and 12% 

dol lar growth; Merck & Co’s (USA) Cozaar (losartan) is sec ond with a 16.3% mar ket share, down 5% 

over the pre vi ous year, and in fourth place, Boehringer Ingelheim’s (Ger many) Micardis (irbesartan), 

with a 8.9% mar ket share and 16% dol lar growth. Benicar (olmesartan medoxmil) took fifth place with 

8.5% and 24% growth. Blopress led the Jap a nese mar ket in the same pe riod with 30.9% mar ket share 

and 4% fixed-dollar growth. 

Blopress was also the best sell ing phar ma ceu ti cal prod uct in Ja pan in the year end ing Sep tem ber 2008 

ac cord ing to IMS. 

Takeda is de vel op ing a fixed-dose com bi na tion of candesartan with the cal cium an tag o nist amlodipine in 

Ja pan, un der go ing phase III de vel op ment This will be a com bi na tion of two of Ja pan’s best sell ing drugs. 

In Ja pan doc tors of ten co-pre scribe an ARB and cal cium an tag o nist to achieve blood pres sure tar gets with 

sin gle treat ment said to achieve this in only half of pa tients. Other com pa nies de vel op ing such com bi na - 

tions in Ja pan are Daiichi Sankyo with Oletec (olmesartan) + Calblock (azelnidipine), ex pected to be filed 

for ap proval in 2009 and Novartis with Diovan (valsartan) and amlodipine. In the US Novartis ob tained 

ap proval for its Exforge (valsartan + amlodipine) in the US in June 2007 and Daiichi Sankyo for Azor 

(olmesartan + amlodipine) in September 2007. 

Hyzaar/Cozaar (losartan) was ap proved by the FDA in April 2005 as the first and only fixed-dose com bi - 

na tion hy per ten sion med i cine to help pre vent stroke in pa tients with hy per ten sion and left ven tric u lar 

hypertrophy. 

Sales/An a lyst Com ment: In the year to March 31 2008 (fis cal 2007) ac cord ing to Takeda, con sol i - 

dated Blopress global sales were up 8.2% to Yen223.1 bil lion. Ac cord ing to IMS, Blopress was Takeda’s 

num ber three in ter na tional phar ma ceu ti cal prod uct in the 12-month pe riod to the end of Sep tem ber 

2008, mak ing up 11% of cor po rate sales, up 6% in fixed rate dol lar terms. An a lysts at Mor gan Stan ley 

(Au gust 2008) fore cast con sol i dated Blopress sales of Yen246.8 bil lion by the year ending March 2013. 

BLOPRESS COMP (candesartan cilexetil+ hy dro chlo ro thi a zide), an AIIA/di uretic com bi na tion for hy per - 

ten sion, has been de vel oped by Takeda and was first launched in Swe den in 1998. Takeda has now 

launched the com bi na tion prod uct in a num ber of mar kets, in clud ing Ger many (as Blopress R), Aus tria 

(as Blopress Plus), It aly (as Blopresid), Swit zer land and Thai land (Blopress Plus) and France (as 

Cokenzen). In a num ber of other mar kets, the com bi na tion is mar keted by li censee AstraZeneca (UK) 

and in some mar kets, the com bi na tion is co-mar keted by Takeda and AstraZeneca. The com bi na tion was 

launched in the USA by AstraZeneca as Atacand HCT. 

In Feb ru ary 2009 AstraZeneca re ported that its fil ing for Atacand Plus, 32 mg (candesartan cilexetil) + 

12.5 mg (hy dro chlo ro thi a zide) and 32 mg/25 mg for mu la tions, has been ap proved in 11 EU states and 

Ice land for the treat ment of hy per ten sive pa tients; Swe den acted as the ref er ence mem ber state. 

Takeda and AstraZeneca’s com bi na tion of candesartan cilexetil and hy dro chlo ro thi a zide is avail able in 

most mar kets world wide for the treat ment of hy per ten sion. It was filed again in Ja pan with half the dose 

of hy dro chlo ro thi a zide in March 2008 and ap proval of Ecard in two dos age forms for the treat ment of hy - 

per ten sion was granted in Jan u ary 2009. The dose of hy dro chlo ro thi a zide for both was set at 6.25mg 



(one-quar ter the low est ap proved dose) as the side ef fects are dose de pend ent, along with the two most 

commonly used doses of candesartan (4 and 8mg). 

Com pe ti tion: Novartis also ob tained ap proval in Ja pan for its Co-DIO, com bin ing its Diovan (valsartan) 

with hy dro chlo ro thi a zide in Jan u ary 2009. Both join Banyu’s losartan + hy dro chlo ro thi a zide com bi na tion 

Preminent al though this is avail able in one strength only com pared with two strengths for Takeda’s 

Ecard and Novartis’ Co-DIO. Co-DIO how ever uses two dos ages of hy dro chlo ro thi a zide (6.25mg and 

12.5mg) along with the same dose of valsartan which it says will en able cli ni cians to se lect the more ap - 

pro pri ate one con sid er ing the risk of ad verse events due to hy dro chlo ro thi a zide. Takeda con firmed that 

data from clin i cal tri als re vealed com pa ra ble hypotensive ef fi cacy with Ecard (4mg candesartan + 

6.25mg hy dro chlo ro thi a zide) to candesartan 8mg and a more po tent hypotensive ef fect using Ecard 

(8mg + 6.25mg hydrochlorothiazide) to candesartan 8mg. 

Takeda’s Blopress was the third best sell ing AIIA in its class (C9C, To tal An gio ten sin II An tag o nists, Plain) 

in the 12 months to Sep tem ber 2008, with 11.4% mar ket share and 6% dol lar growth, ac cord ing to IMS. 

Novartis’ (Swit zer land) Diovan (valsartan) is mar ket leader with a 26.3% mar ket share and 12% dol lar 

growth; Merck & Co’s (USA) Cozaar (losartan) is sec ond with a 16.3% mar ket share, down 5% over the 

pre vi ous year, and in fourth place, Boehringer Ingelheim’s (Ger many) Micardis (irbesartan), with a 

8.9% mar ket share and 16% dol lar growth. Benicar (olmesartan medoxmil) took fifth place with 8.5% 

and 24% growth. 

Sales/An a lyst Com ment: In the year to March 31 2008 (fis cal 2007) ac cord ing to Takeda, con sol i - 

dated Blopress global sales were up 8.2% to Yen223.1 bil lion. In the 12-month pe riod to the end of Sep - 

tem ber 2008, Blopress Comp was Takeda’s num ber nine in ter na tional phar ma ceu ti cal prod uct, mak ing 

up 1.3% of cor po rate sales, up 7% in fixed rate dol lar terms, ac cord ing to IMS. An a lysts at Mor gan Stan - 

ley (Au gust 2008) fore cast con sol i dated Blopress sales of Yen246.8 bil lion by the year ending March 

2013. 

CALSLOT (manidipine), a once-daily cal cium an tag o nist, was launched in Ja pan in 1990 for hy per ten - 

sion. 

Li cens ing: Manidipine was li censed-out to Chiesi (It aly) for mar ket ing in Eu rope and Brazil. Takeda 

co-mar kets the prod uct in It aly with Chiesi as Vascoman. Chiesi first launched it in It aly as Iperten in 

1996. In 2000, Chiesi launched it in Brazil as Manivasc. Chiesi com pleted the Eu ro pean mu tual rec og ni - 

tion pro ce dure in 2001, and in 2003, launched manidipine in Spain as Artedil and in Greece as Manyper. 

It was launched in Ger many as Manyper in and in Tu ni sia as Iperten in 2004. In 2005, it was launched in 

France as Iperten. Iperten was launched in Mo rocco in March 2006. 

Lifecycle Man age ment: Li censee Chiesi has de vel oped a com bi na tion of the Takeda ACE in hib i tor 

delapril and manidipine, with the trade name Vi vace. It was launched in Aus tria in 2005 and in Ger many 

in Feb ru ary 2006. In March 2006, it was launched in Brazil as Hipertil. Delapril, and manidipine were 

orig i nally de vel oped by Takeda, and li censed by Chiesi for Eu rope and Brazil. Takeda does not ap pear to 

be de vel op ing this com bi na tion product in Japan, however. 

Sales/An a lyst Com ment: With sales of Yen5 bil lion in fis cal 2007 (end ing March 2008), an a lysts at 

Mor gan Stan ley (Au gust 2008) fore cast a drop in sales to Yen3.5 bil lion by the year end ing March 2013. 

NIASPAN (ni a cin ex tended re lease) is ap proved a treat ment of mul ti ple lipid dis or ders, and was first 

launched in 1997. It is the only once-daily ex tended-re lease for mu la tion of ni a cin avail able in the USA for 

this indication. 

Li cens ing: Takeda (through TPNA) signed an agree ment with Kos (now Abbott, USA) in No vem ber 2003 

to co-pro mote the prod uct in the USA from Jan u ary 2004. An iden ti cal agree ment was signed for Kos’s 

other cho les terol prod uct, Advicor (ni a cin/lovastatin ex tended re lease). Both agree ments are due to last 



three years, but can be ex tended. If the com pa nies do not re new the part ner ship, Takeda will be el i gi ble 

to re ceive de clin ing tail pay ments for a pe riod of three years fol low ing 2006. Un der the agree ment, 

TPNA’s 1,000-strong US sales force will co-pro mote the prod ucts and Takeda will re ceive an un dis closed 

per cent age of net sales for the Kos’s (now Abbott’s) cur rent cho les terol franchise above a specific 

baseline level. 

Lifecycle Man age ment: Kos an nounced in July 2006 that it had sub mit ted a sup ple men tal NDA to the 

US FDA, seek ing the ap proval of a com plete dos age range of Niaspan CF, a caplet for mu la tion of the 

prod uct. The Niaspan CF range in cludes an op ti mized 1000mg caplet formulation. 

� Central Nervous System Agents 

ANPEC TAKEDA (mor phine hy dro chlo ride) was launched in Ja pan in 1991. It was co-launched with 

Tanab (now Mitsubishi Tanabe Pharm), Sankyo (now Daiichi Sankyo), Shionogi and Dainippon (now 

Dainippon Sumitomo, all Ja pan), which mar ket it as Anpec Tanabe, Anpec Sankyo etc. A con cen trated 

high-dose ver sion of mor phine hy dro chlo ride has been filed in Ja pan by Takeda and its joint de vel op ment 

part ners (with the lab o ra tory code MH 200), for the treat ment of se vere pain due to cancer. 

EURODIN (estazolam), an in ter me di ate-act ing benzo diaz epine, has been mar keted world wide for the 

short-term man age ment of in som nia since 1967. It was orig i nally de vel oped by the Takeda/Abbott joint 

ven ture, TAP (USA), dis solved in May 2008. In 2003, estazolam was launched in Tai wan, Rus sia and Lat - 

via as a treat ment for insomnia. 

HIRTONIN (protirelin), a thyrotropin-re leas ing hor mone, has been on the mar ket for some years as a 

di ag nos tic and ther a peu tic agent and was launched by Takeda in Ja pan as Hirtonin in 1978 as a 

nootropic. In 1988, Takeda Italia launched it as a nootropic un der the name Irtonin. 

MS CONTIN TAKEDA (mor phine sul fate) is a slow-re lease mor phine prod uct, orig i nally de vel oped by 

Mundipharma (Swit zer land). It was li censed out to Takeda for Ja pan and launched there in 1989. It was 

co-de vel oped with Tanabe (now Mitsubishi Tanabe Pharma), Sankyo (now Daiichi Sankyo), Shionogi and 

Dainippon (now Dainippon Sumitomo), which co-mar ket the prod uct in Ja pan as MS Contin Tanabe, 

MS Contin Sankyo etc. A high-dose con cen trated ver sion was launched in Japan in 1995. 

NICHOLIN (citicoline), an oral neuroprotective is avail able in more than 70 coun tries for the treat ment 

of ischemic stroke. Takeda sells the drug in Ja pan. 

OPSO TAKEDA (mor phine hy dro chlo ride) is an oral for mu la tion pre-pre pared in dos age units of 5mg 

and 10mg. It is in di cated for mod er ate to se vere pain in can cer, and was launched in Ja pan in 2003. 

OXYCONTIN TAKEDA (oxycodone) is a re tard-film coated tab let for mu la tion used for mod er ate to se - 

vere pain in var i ous types of can cer. It was launched in Ja pan in 2003. 

PREPENON TAKEDA (in ject able mor phine hy dro chlo ride) was launched in Ja pan in 2001, through a 

part ner ship with Terumo (Ja pan). It is in di cated for the re lief of pain in can cer pa tients. Takeda is re spon - 

si ble for sales and Terumo for de vel op ment and pro duc tion. Prepenon is sold in pre-filled sy ringes, in - 

creas ing con ve nience for pa tients treat ing themselves at home. 

PROVIGIL (modafinil), a non-am phet amine psychostimulant for narcolepsy and id io pathic 

hypersomnia. It was first launched in France in 1994 for the treat ment of narcolepsy and id io pathic 

hypersomnia, and has sub se quently been launched in most mar kets world wide, in clud ing the USA, Eu - 

rope, Can ada and Aus tra lia, and is await ing ap proval in Ja pan for this in di ca tion. In Au gust 2006 the US 

FDA is sued a non-ap prov able let ter for Cephalon’s s NDA for the use of modafinil in the treat ment of at - 



ten tion def i cit hy per ac tiv ity dis or der (ADHD) in chil dren and ad o les cents. Li censee Cephalon (USA) has 

dis con tin ued fur ther development of modafinil for this indication. 

Li cens ing: Lafon (France) holds pat ent rights to modafinil, and Cephalon has li censed rights to the prod - 

uct in the USA, UK, Ire land, Ja pan, It aly, Mex ico, Latin Amer ica and sev eral Asian coun tries. In June 

2006, Cephalon and Takeda an nounced that they had en tered into an agree ment, un der which Takeda 

will co-pro mote Provigil in the USA. The three-year deal will have an op tion to re new an nu ally, and 

Cephalon will also have an op tion to use Takeda to pro mote Nuvigil (armodafinil). Cephalon will pay 

Takeda a roy alty based on cer tain sales cri te ria for both prod ucts. Cephalon will re tain all re spon si bil ity for 

de vel op ment, dis tri bu tion and sales of modafinil. 

ROZEREM (ramelteon), a melatonin ag o nist de vel oped by Takeda, was launched in 2005 in the USA for 

in som nia char ac ter ized by dif fi culty with sleep on set. Rozerem is the first and only non-sched uled pre - 

scrip tion sleep med i ca tion to be ap proved (thus al low ing phy si cians to pre scribe for long-term use in 

adults) and also is the first pre scrip tion in som nia med i ca tion with a novel mech a nism of ac tion to be 

approved in the last 35 years. 

Phase III tri als were on go ing in Ja pan and in Feb ru ary 2008, Takeda sub mit ted an NDA in Ja pan for ap - 

proval of ramelteon in the treat ment of pri mary insomnia. 

In March 2007 Takeda sub mit ted a Mar ket ing Au tho ri za tion Ap pli ca tion to the Eu ro pean Med i cines 

Agency (EMEA) for this in di ca tion. Takeda’s ap pli ca tion was sub mit ted through the cen tral ized pro ce dure 

and is sup ported by clin i cal trial data from 8100 pa tients aged 18 to 93. Takeda an nounced in Sep tem ber 

2008 that it has with drawn its MAA for ramelteon in the EU, seek ing ap proval for the treat ment of pri mary 

in som nia. The de ci sion fol lows the anal y sis of ad di tional clin i cal data, col lected af ter Takeda’s re quest for 

re-ex am i na tion of the CHMP’s neg a tive opin ion in May 2008. Takeda re mains com mit ted to gain ing EU 

ap proval of the agent, and plans to submit a new MAA to the EMEA in the future. 

In March 2007, the FDA called for stron ger warn ings for 13 sleep ing pills in clud ing Rozerem of dan ger ous 

po ten tial side ef fects like al ler gic re ac tions and sleep driv ing. The same month, the FDA also said that TV 

ad ver tise ments of Rozerem that in cluded im ages of chil dren vi o lated rules as Takeda does not have ap - 

proval for pe di at ric use and it is not known if Rozerem is safe in ad o les cents due to po ten tial ef fects on re - 

pro duc tive hor mones. Fur ther more, Takeda failed to sub mit the ad ver tise ment be fore run ning and while 

the FDA does not have to sign off be fore run ning, companies are required to submit beforehand. 

Clin i cal Data: The FDA ap proval was backed by data from more than 4,200 pa tients aged 18 to 93, in - 

clud ing a 472 pa tient trial with sin gle doses daily for up to a year. Rozerem was ad di tion ally shown to be 

safe in adults with COPD or mild-to-mod er ate sleep apnea as well as el derly adults. Clin i cal stud ies also 

re vealed that Rozerem had no more po ten tial for abuse or be hav ioral im pair ment than pla cebo, even at 

up to 20 times the pro posed therapeutic dose. 

In May 2007, a new study pre sented by TPNA showed that ramelteon did not im pair mid dle-of-the-night 

bal ance, mo bil ity or mem ory per for mance in older adults with in som nia over pla cebo un like the zolpidem 

treated pa tients who dem on strated im paired per for mance in these mea sures com pared with placebo. 

Lifecycle Man age ment: Phase II tri als are be ing con ducted in the USA for sleep/cir ca dian rhythm dis - 

or ders/jetlag. Ramelteon spe cif i cally tar gets melatonin ML-1 re cep tors within the hy po tha lamic re gion of 

the brain.Takeda had ex pressed in tent to ex tend the use of Rozerem to treat Alz hei mer’s dis ease (TAK 

375) but phase III tri als were dis con tin ued in 2007 fol low ing in suf fi cient num bers of pa tients re cruited 

meeting inclusion criteria. 

Com pe ti tion: The US in som nia mar ket is fore cast to grow sub stan tially but Takeda is not the only one 

hop ing to tap into this growth. In 2005, Sepracor’s in som nia treat ment, Lunesta (eszopiclone), hit the 

mar ket, around six months ahead of Rozerem. Lunesta of fers the ad van tage of long du ra tion of ac tion 



(six hours sleep) com pared with other hyp notic drugs on the mar ket like sanofi-aventis’ (France) 

Stilnox/Ambien (zolpidem) and Wyeth/King’s (USA) So nata (zaleplon), which of fer just three hours 

sleep and thus is more of a sleep in ducer than maintainer. 

In the 12 month pe riod to the end of Sep tem ber 2008, Rozerem climbed to be come the fourth lead ing 

prod uct in the global hyp notic mar ket ac cord ing to IMS with 2.4% share down 4% (fixed dol lar growth) 

over the pre vi ous year. Stilnox/Ambien cur rently dom i nates with one-third of this mar ket 32.6% mar ket 

share al though sales de clined by 46% fixed rate dol lar growth. Ambien first hit the US mar ket in 1993, of - 

fer ing an al ter na tive to the older benzodiazepines such as Roche’s Val ium (di az e pam). US ex clu siv ity for 

Ambien was due to ex pire in Oc to ber 2006, but in Sep tem ber 2005, a con trolled re lease ver sion 

(Ambien CR) was ap proved by the FDA for the treat ment of in som nia, and with a broader ap pli ca tion 

than its par ent, with out the re stric tion of use to 7-10 days. Pre vi ously Lunesta had been the only prod uct 

with out this re stric tion, while Rozerem is the only prod uct not des ig nated as a con trolled sub stance. 

sanofi-aventis’s other benzo diaz epine an tag o nist Imovane (zopiclone) now wits in fifth place in this 

class with 2.4% market share and 17% growth. 

While Lunesta has been crit i cized for its un pleas ant taste, an a lysts be lieved it has sig nif i cant com mer cial 

po ten tial and in the year end ing Sep tem ber 2008, ac cord ing to IMS it took sec ond po si tion with a 17% 

mar ket share and 7% fixed rate dol lar growth. Num ber three was Boehringer Ingelheim’s Lendormin 

(brotizolam), with a 3.0% mar ket share and up 4% over the previous year. 

Wyeth/King’s (USA) So nata (zaleplon) other benzo diaz epine an tag o nist has fallen to eighth place, with a 

1.4% mar ket share, and with sales down 37% in fixed rate dol lar terms. 

Many an a lysts are con tent with Takeda’s view that Rozerem of fers the best side ef fect pro file with vir tu - 

ally no abuse po ten tial, re bound in som nia, with drawal ef fects or im pact on mo tor func tion (and no hang - 

over like ef fects the next day). All other pre scrip tion in som nia drugs have been des ig nated sched ule IV 

con trolled sub stances by the US Drug En force ment Ad min is tra tion, a cat e gory Rozerem avoided be cause 

of lack of ev i dence of de pend ency or abuse, and this is a real sell ing point for Takeda. The prod uct acts on 

neuronal ac tiv ity in the brain’s suprachiasmatic nu cleus to pro mote phys i o log i cal rather than sed a tive 

sleep. Other an a lysts have ex pressed con cern over the nar row in di ca tion for Rozerem, which does not in - 

clude sleep main te nance, a strong sell ing point for Lunesta; an a lysts at Merrill Lynch note that the treat - 

ment of sleep main te nance in som nia represents a larger market opportunity than sleep onset insomnia. 

A ma jor com pet i tor was ex pected to be indiplon, which Neurocrine Bio sci ences (USA) had part nered with 

Pfizer (USA). Indiplon has been dem on strated to be as ef fec tive as Ambien in treat ing in som nia with out 

caus ing next-day re sid ual ef fects. The drug hit prob lems in 2006, how ever, when the FDA gave only con - 

di tional ap proval, and the com pany has to con duct an other trial. In June 2007, Neurocrine Bio sci ences 

re sub mit ted the NDA for indiplon cap sules, but an a lysts are now skep ti cal about the prod uct’s po ten tial 

with out Pfizer’s mar ket ing mus cle be hind it af ter the com pany ter mi nated its agree ment with Neurocrine. 

In July 2008, Neurocrine Bio sci ences (USA) is sched uled to be meet ing with the FDA to dis cuss its De - 

cem ber 2007 ‘ap prov able’ let ter for indiplon 5 and 10mg cap sules; the agency re quested an ob jec - 

tive/sub jec tive clin i cal trial in the el derly, a safety study as sess ing the rates of ad verse events oc cur ring 

with indiplon com pared with a prod uct on the mar ket, and a pre clin i cal study eval u at ing the ad min is tra - 

tion of indiplon dur ing the third tri mes ter of preg nancy — al most halv ing Neurocrine’s share price to an 

eight-year low. Indiplon is a nonbenzodiazapine agonist of the benzodiazepine site on GABA receptors. 

At the end of Jan u ary 2008, Somaxon (USA) filed Silenor (doxepin) for ap proval in in som nia; this is ac - 

tu ally an old, tricyclic an ti de pres sant, and is thus not ex pected to be come a sched uled prod uct. Silenor 

could be come the first non sched uled in som nia treat ment to help pa tients fall asleep and main tain sleep 

through out the night giv ing a dis tinct mar ket ing ad van tage over Rozerem which is in di cated spe cif i cally 

for in som nia marked by dif fi culty with sleep on set. Rozerem is the first sleep aid with a new mech a nism of 

ac tion launched in over 30 years and the only pre scrip tion treat ment for this use not to be des ig nated as a 



con trolled sub stance; the mech a nism of ac tion of Silenor is not fully un der stood but works by block ing 

the re lease of his ta mine at the H1 re cep tor (most approved insomnia medications act via GABA 

receptors). 

New in som nia ther a pies in de vel op ment in 2008 in cluded sanofi-aventis’ eplivanserin and 

volinanserin, 5-HT2A re cep tor an tag o nists both in phase III tri als. Reg u la tory fil ings for eplivanserin 

were ex pected dur ing the sec ond half of 2008. 

Also at the phase III stage is Akzo No bel’s (Neth er lands) esmirtazapine, an other 5-HT2A an tag o nist. 

An a lysts ap pear to have high hopes for Vanda’s tasimelteon (VEC-162), a melatonin MT1/MT2 ag o nist 

that be gan phase III tri als in 2006, and like Rozerem (which af fects just the MT1 re cep tor), should not be 

a con trolled sub stance. Vanda an nounced pos i tive top-line re sults from one phase III study in June 2008, 

where tasimelteon showed good ef fi cacy at treat ing chronic in som nia over a four-week pe riod. The com - 

pany be lieves that the com pound may also have po ten tial as a ther apy for cir ca dian rhythm sleep 

disorders. 

Lilly is de vel op ing pruvanserin, a 5-HT2A an tag o nist li censed from Merck KGaA, in phase II tri als, and in 

March 2007 an nounced the ac qui si tion of Hypnion, which fo cuses on in som nia ther a pies. Its lead com - 

pound, HY10275, also in phase II tri als, tar gets 5-HT2A and the his ta mine H1 re cep tor. Lilly hopes nei - 

ther drug would be a controlled substance. 

At the end of 2007, Actelion (Swit zer land) ini ti ated a phase III study with almorexant, a first-in- class 

orexin OX1/OX2 re cep tor an tag o nist, in chronic pri mary in som nia. In 2008 GlaxoSmithKline en tered a 

$3.3 bil lion deal over this drug with Actelion. GSK is also de vel op ing an orexin an tag o nist, in phase II tri - 

als: the neuropeptide plays a key role in main tain ing wake ful ness and reg u lat ing the sleep-wake cy cle, 

and these new drugs are gar ner ing a lot of attention. 

A num ber of com pa nies are de vel op ing novel for mu la tions of zolpidem. In De cem ber 2008, the FDA ap - 

proved NovaDel’s Zolpimist, an oral spray prod uct for the short-term treat ment of in som nia. In May 

2008, Orexo (Swe den) sub mit ted a 505(b)(2) NDA for Sublinox, which uses the com pany’s sublingual 

tab let tech nol ogy, also as a short-term in som nia ther apy; Meda (Swe den) has the global rights to com - 

mer cial ize Sublinox, which Orexo claims takes ef fect 30% faster than Ambien. In Oc to ber 2008, 

Transcept filed a US NDA for In ter mezzo, an other sublingual formulation of zolpidem. 

Sales/An a lyst Com ment: Backed by an ag gres sive Yen25 bil lion ($231.6 mil lion) sales cam paign, 

with a di rect-to-con sumer (DTC) com po nent that started in 2006, Takeda aims for Rozerem to be come 

its fifth block buster. Sales jumped 25% in the US to $111 mil lion in the year end ing March 2008; Yen12.6 

bil lion, from Yen10.3 bil lion in the year to March 2007) and Mor gan Stan ley an a lysts (Au gust 2008) fore - 

cast sales ris ing to Yen33.5 bil lion by the year end ing March 31 2013. Some Jap a nese an a lysts have es ti - 

mated that peak global sales for Rozerem could reach Yen60-100 billion. 

� Genitourinary System/Sex Hormones 

IXENSE/UPRIMA (sublingual apomorphine), a do pa mine ag o nist, is in di cated in the treat ment of erec - 

tile dys func tion (ED). It acts on the CNS and has a mech a nism of ac tion com pletely dif fer ent from that of 

ex ist ing ED prod ucts. The drug has shown ef fec tive ness in men with erec tile dys func tion of or ganic, psy - 

cho genic, and mixed eti ol ogy. Cau tion is rec om mended in pa tients us ing antihypertensive agents, ni - 

trates or other drugs which might lower blood pres sure. Apomorphine has been used for many years in 

the treat ment of Par kin son’s dis ease. It was launched in France, It aly and Ger many as Ixense by Takeda 

in 2001, and in Thai land in 2002. In the UK, it was co-pro moted by Takeda and Abbott as Uprima. In the 

rest of the EU, Takeda will use the Ixense trade name and Abbott Uprima. Li censee Abbott has launched 

the prod uct as Uprima in a num ber of mar kets in Eu rope and Latin America, as well as New Zealand. 



In the USA, the prod uct was in de vel op ment with TAP Pharmaceuticals, the Takeda Abbott jv which was 

con cluded in May 2008 with Takeda re tain ing rights to this prod uct. TAP started mar ket ing the drug in the 

USA in 2003. 

Li cens ing: Apomorphine was li censed to TAP by Pentech. TAP holds ex clu sive world wide rights to 

apomorphine for the treat ment of Par kin son’s Dis ease. An agree ment be tween TAP and Takeda giv ing 

Takeda rights to the prod uct out side Eu rope and the USA was ter mi nated in 2001. Pharmacia (now Pfizer, 

USA) has held rights to an intranasal for mu la tion for erec tile dys func tion and fe male sex ual dysfunction 

since 2002. 

Com pe ti tion: Abbott has stated that it has high hopes for Uprima and be lieves that it will of fer pa tients a 

prom is ing new op tion. The ED mar ket is now dom i nated by a bat tle be tween the PDE-V in hib i tors Pfizer’s 

Viagra (sildenafil), Bayer’s Levitra (vardenafil) and Lilly’s Cialis (tadalafil). In the year end ing Sep tem - 

ber 2008, Viagra was still the world’s lead ing ED drug with 44.5% mar ket share, up 4% (fixed dol lar 

growth) over the pre vi ous year, fol lowed by Cialis with 33.4% share (up 18%) and then Levitra with 13% 

(up 10%). 

� Musculoskeletal System Agents 

BENET (risedronic acid), a bisphosphonate com pound, was launched in Ja pan in May 2002 by Takeda for 

the treat ment of postmenopausal os teo po ro sis. Sanofi-aventis (France) is co-mar ket ing the prod uct in 

Ja pan as Actonel. In June 2004, the Jap a nese side-ef fect warn ing state ments for risedronic acid were 

re vised fol low ing lo cal re ports of ADRs. The list of se ri ous po ten tial side-ef fects for the prod uct, along with 

Pfizer’s Cardenalin (doxazosin), has been ex panded to in clude hepatic dys func tion and jaun dice, as well 

as hep a ti tis for Cardenalin. A once-a-week for mu la tion of risedronic acid is avail able in the USA, Can ada 

and a num ber of other coun tries, now in clud ing Japan following approval in April 2007. 

Li cens ing: Orig i na tor Procter & Gam ble (USA) li censed it out to Aji no mo to (Ja pan) for Ja pan in 1992, 

where it was co-de vel oped with sublicensees Takeda and Aventis (now sanofi-aventis). Risedronic acid 

pre vents bone cal cium from be ing re ab sorbed by the body. Risedronic acid was launched in the USA in 

1998 as Actonel for the treat ment of Paget’s dis ease by P&G and Aventis. It is now widely avail able for 

the treat ment of Paget’s dis ease and the pre ven tion and treat ment of os teo po ro sis. In 1997, P&G and 

Aventis agreed to co-de velop and co-mar ket risedronic acid worldwide. 

Clin i cal Data: In 2004, Aventis re ported re sults from a five-year pla cebo-con trolled paired bi opsy study 

of risedronic acid in 86 postmenopausal women with os teo po ro sis. Pa tients were treated with risedronic 

acid or pla cebo, and bone tis sue bi op sies taken from 21 and 27 pa tients in each treat ment group were 

histologically ex am ined at base line and af ter five years of treat ment. Re sults showed a sig nif i cant mod er - 

ate and sus tained de crease in bone turn over in pa tients treated with risedronic acid, with no sig nif i cant 

de crease in pla cebo. New bone was nor mal and of good qual ity. Bi opsy data showed a mod er ate sup pres - 

sion of bone re mod el ing, in line with es ti mated sup pres sion of bone turnover in patients treated with 

risedronic acid. 

Lifecycle Man age ment: The prod uct was filed for ap proval in Paget’s dis ease in Ja pan in July 2007 and 

ap proval granted in July 2008. 

Com pe ti tion: Benet was the world’s num ber 10 bone cal cium reg u la tor in the 12-month pe riod to the 

end of Sep tem ber 2008, ac cord ing to IMS, with a mar ket share of 1.5% and 2% de cline in fixed rate dol - 

lar growth. Procter & Gam ble’s risedronic acid prod uct Actonel led the class with a 18.4% mar ket share 

but a sales de cline of 1% in fixed rate dol lar terms. Novartis’ Zometa (zoledronic acid) was num ber two 

with 16.1% mar ket share and up 14% over the pre vi ous year. Num ber three was Merck & Co’s Fosamax 

(alendronate), with a 15.2% down 47% over the previous year. 



Sales/An a lyst Com ment: With sales of Yen16.5 bil lion in fis cal 2007 (end ing March 2008), up from 

Yen16.2 bil lion the pre vi ous year, Mor gan Stan ley an a lysts (Au gust 2008) pre dict sales of Yen26.0 bil lion 

by the year end ing March 2013. 

DASEN (serrapeptase), an orally-ef fec tive anti-in flam ma tory bac te rial pro te ase, was first launched in 

Ja pan in 1968. It was launched in France in 1981, and in Ger many in 1985 as Aniflazym. 

Sales/An a lyst Com ment: With sales of Yen7.7 bil lion in fis cal 2007 (end ing March 2008), down from 

Yen8.1 bil lion the pre vi ous year, Mor gan Stan ley an a lysts (Au gust 2008) pre dict sales of Yen7 bil lion by 

the year end ing March 2013. 

ENBREL (etanercept), a mod u la tor of in flam ma tion, was launched in Ja pan in March 2005 fol low ing ap - 

proval in Jan u ary for the treat ment of rheu ma toid ar thri tis (RA) in pa tients who have had an in ad e quate 

re sponse to ex ist ing ther a pies. Enbrel in hib its tu mor ne cro sis fac tor (TNF). In June 2008, Wyeth and 

Takeda launched a once-fort nightly pre-filled self-in jec tion sy ringe for mu la tion of Enbrel, re duc ing the 

healthcare bur den. Wyeth mar kets etanercept out side North Amer ica and co-pro motes the agent in 

North America with licensor Amgen. 

Enbrel was first launched in the USA in 1998 for the re duc tion in signs and symp toms of mod er ately to se - 

verely ac tive rheu ma toid ar thri tis in adult pa tients who have an in ad e quate re sponse to one or more dis - 

ease mod i fy ing anti-rheu matic drugs (DMARDs), and can be used in com bi na tion with methotrexate in 

pa tients who do not re spond ad e quately to methotrexate alone. The prod uct is in di cated for the treat - 

ment of RA, psoriatic ar thri tis, an ky los ing spondylitis, and pso ri a sis, and is ad min is tered as a sub cu ta ne - 

ous in jec tion twice-weekly. In the USA, the FDA ap proved Enbrel for ju ve nile RA (1999), for psoriatic 

ar thri tis in adults (2002), for the treat ment of ac tive an ky los ing spondylitis in adults (2003), as a treat - 

ment to im prove phys i cal func tion in pa tients with mod er ate-to-se vere ac tive RA (2003) and an ex - 

panded in di ca tion to im prove phys i cal func tion in pa tients with psoriatic ar thri tis (June 2005). In 2004, 

the FDA ap proved a once-weekly 50 mg/mL pre-filled sy ringe for mu la tion of Enbrel for the treat ment of 

all ap proved adult in di ca tions. This ad di tional for mu la tion eliminates the need to mix the drug prior to 

injection and allows for once-weekly injections. 

In Eu rope, Enbrel was ap proved for use in mod er ate-to-se vere RA and polyarticular course ju ve nile 

chronic ar thri tis in chil dren aged 4-17 in 2000, for psoriatic ar thri tis in adults (2002), and for of ac tive an - 

ky los ing spondylitis in adults in 2003. From 1999-2003 it was rolled out in Eu rope, Can ada, Asia and Latin 

Amer ica. It is also be ing stud ied in a num ber of other in di ca tions. In 2006, Wyeth ini ti ated a phase II trial 

of etanercept in Ja pan in pa tients with ju ve nile RA. In 2009 ap proval was granted for treat ment of chronic 

se vere plaque pso ri a sis in children aged eight to 17 years. 

Li cens ing: Enbrel was de vel oped by Immunex (now part of Amgen, USA) and is co-mar keted by Wyeth 

(USA) in the USA. Wyeth KK, in which Takeda pre vi ously held a stake, is de vel op ing the drug in Ja pan. 

Wyeth has rights to Enbrel out side the USA for all in di ca tions out side on col ogy, and the drug will be 

co-mar keted with Takeda in Ja pan. Enbrel’s Jap a nese ap proval trig gered changes in the struc ture of 

Wyeth’s 60%-owned jv with Takeda. Wyeth’s grad ual planned buy-out of Takeda’s share will con vert the 

op er a tion into a wholly-owned sub sid iary. Un der the agree ment, Takeda will con tinue to dis trib ute Wyeth 

prod ucts in Ja pan and will co-pro mote Enbrel and co-pro mote or co-market two other products. 

Clin i cal Data: In De cem ber 2008, Wyeth and Takeda pub lished re sults from a 151-Jap a nese pa tient 

study show ing that co-ad min is tra tion of etanercept with methotrexate gave better re sults than 

etanercept alone. 

In April 2007, at the An nual Sci en tific Meet ing of the Ja pan Col lege of Rheumatology, data from 

post-mar ket ing sur veil lance on data from over 7,000 pa tients ad min is tered Enbrel since April 2005. High 

ef fi cacy was shown with marked im prove ment in 28.9%; mod er ate im prove ment in 55.2% and no im - 



prove ment in 15.9%; the ef fi cacy rate was 84.1% (de ter mined by the DAS28 dis ease ac tiv ity score). Ad - 

verse events were re ported in 30.6% and 5.7% were serious. 

Com pe ti tion: With an es ti mated 700,000 RA suf fer ers (mostly women) in Ja pan, fewer than half of 

which are treated, Ja pan rep re sents a po ten tially lu cra tive mar ket and com pe ti tion is in ten si fy ing. 

Enbrel’s, main ri val, John son & John son’s Remicade (infliximab), was the first TNF-al pha an tag o nist to 

reach the Jap a nese mar ket with its 2002 launch for RA (un re spon sive to other DMARDS). Remicade has 

the ad van tage of in tra ve nous ad min is tra tion once ev ery eight weeks, com pared with Enbrel’s self-in jec - 

tion twice weekly. Whilst Remicade acts to de stroy cells pro duc ing TNF al pha, Enbrel acts sim ply to in hibit 

them, be ing an an ti body-like fu sion pro tein as op posed to an an ti body. An other ad di tion to the 

monoclonal an ti body mar ket is Abbott‘s (USA) Humira (adalimumab), a fully hu man monoclonal an ti - 

body di rected against tu mor ne cro sis fac tor-al pha, li censed to Eisai/Hokuriku‘s (Japan), where it won 

approval in April 2008. 

Ac cord ing to IMS, in the year end ing Sep tem ber 2008, Enbrel was Ja pan’s lead ing ‘to tal spe cific 

anti-rheu matic’ (M1C class) with 49.9% share of the mar ket and 58% fixed dol lar growth over the pre vi - 

ous year. Enbrel also dom i nated the world wide M1C mar ket with 53.4% share and 9% fixed dol lar 

growth, fol lowed by Humira with 35.6% share, up 41%. Other sig nif i cant prod ucts in the M1C class in the 

pe riod were BMS’ Orencia, Arava (leflunomide) from sanofi-aventis (France), Wyeth’s Ledertrexate 

(methotrexate) and Amgen’s Kineret. Ac cord ing to IMS, Remicade be longs to the ‘Immunosuppressive 

Agents’ (L4A) ther apy class, which it led in the same time pe riod with a world wide mar ket share of 40.7% 

and registered 16% growth. 

Sales/An a lyst Com ment: Enbrel gen er ated sales of Yen18.8 bil lion in the year end ing March 31 2008, 

and an a lysts at Mor gan Stan ley (Au gust 2008) fore cast sales of Yen45 bil lion by the year end ing March 

2013. 

OSTEN (ipriflavone), an orally-ac tive agent against os teo po ro sis, was launched in Ja pan in 1988. It was 

orig i nally de vel oped by Chinoin (Hun gary), now part of sanofi-aventis (France). For It aly, Chinoin li - 

censed it to Chiesi (It aly). Chiesi has now sub-li censed it to Takeda Italia and the two groups are co-mar - 

ket ing in It aly. Takeda launched it as Iprosten in It aly in 1991, while Chiesi mar kets it as Osteofix. In 

2001, ipriflavone was launched in Mex ico and Co lom bia for the treat ment of postmenopausal 

osteoporosis. 

� Respiratory System Agents 

BRONICA (seratrodast), an orally-ac tive thromboxane A2 re cep tor an tag o nist, was launched on its first 

world mar ket, Ja pan, in 1996, for the treat ment of bron chial asthma. Bronica, the first thromboxane A2 

re cep tor an tag o nist to be launched, is avail able in tab let and gran u lar for mu la tions. It works by in hib it ing 

in creases in air way hy per sen si tiv ity and air way ste no sis by se lec tive an tag o nism of thromboxane A2 re - 

cep tors. In 1998, Takeda re vised the pre cau tions sec tion of the pack age in sert for Bronica, fol low ing re - 

ports of se vere hepatic dis or ders as so ci ated with the drug. Phase II/III tri als were un der way in Eu rope as 

well as phase III in the USA, with the Takeda/Abbott jv TAP, which was dissolved in May 2008. 

� Systemic Anti-Infective Agents 

ACEL-IMUNE (acellular per tus sis + tet a nus + diph the ria vac cine) was first launched in Ja pan in 1981. It 

was li censed to Lederle-Praxis Bi o log i cals, now part of Wyeth (USA), for mar kets out side Ja pan, and was 

launched in the US in 1992. Wyeth has since launched it in a num ber of mar kets. Data sug gests that the 

in ci dence of ad verse re ac tions af ter Acel-Imune, such as pain at the in jec tion site, fe ver and vom it ing are 

re duced by up to 50% com pared to whole cell vaccine. 



BESTCALL (cefmenoxime), an in ject able third-gen er a tion cephalosporin an ti bi otic, was launched in Ja - 

pan by orig i na tor Takeda in 1983. Roche also mar kets it in Ja pan as Bestcall Roche. It is mar keted in 

Ger many and Aus tria by Takeda Pharma as Tacef. Han Il is the li censee for South Ko rea. Senju, Grelan 

and Kyorin sell oph thal mic versions in Japan. 

FAMVIR (famciclovir) is the in ac tive prodrug of penciclovir, which is ef fec tive against her pes sim plex vi - 

rus types 1 and 2. Famciclovir was ap proved for her pes zoster (shin gles) in the UK in De cem ber 1993 and 

was launched in the UK, its first mar ket, in Jan u ary 1994. Famciclovir has since been mar keted in the USA 

(July 1994) and in over 30 other coun tries worldwide. 

Li cens ing: In Sep tem ber 2006, TAP re ported that it had signed a co-pro mo tional agree ment with 

Novartis (Swit zer land) for famciclovir in the USA. Un der the terms of the agree ment, TAP was re spon si ble 

for pro mot ing famciclovir to ob ste tri cians and gy ne col o gists within the USA. Fur ther de tails of the agree - 

ment were not dis closed. In May 2008, Takeda and Abbott con cluded their TAP jv with Takeda re ceiv ing 

rights to the product. 

FIRSTCIN (cefozopran), a semisynthetic, broad-spec trum, parenteral cephalosporin an ti bi otic, was 

launched in Ja pan in 1995 by orig i na tor Takeda and li censee Lederle (now part of Wyeth). Firstcin is par - 

tic u larly ef fec tive against se vere in fec tions caused by staph y lo cocci and enterococci in 

immunocompromised pa tients. It has been ap proved for pe di at ric use and men in gi tis. It will not com pete 

against Takeda’s Pansporin as it is rec om mended for in fec tions that do not respond to Pansporin. 

Sales/An a lyst Com ment: With sales of Yen6.4 bil lion re ported in fis cal 2007 (end ing March 2008), 

Mor gan Stan ley an a lysts (Au gust 2008) fore cast a de cline in sales to Yen6 bil lion by the year to March 

2013. 

GLOVENIN (im mu no glob u lin base), a polyvalent in tra ve nous im mu no glob u lin used to treat se vere in - 

fec tions and im mu no de fi ciency syndromes. 

Sales/An a lyst Com ment: With sales of Yen8.8 bil lion re ported in fis cal 2007 (end ing March 2008), up 

from Yen8.6 bil lion the pre vi ous year, Mor gan Stan ley an a lysts (Au gust 2008) fore cast a slight de cline in 

sales to Yen8.5 bil lion by the year to March 2013. 

PANSPORIN (cefotiam), an in ject able cephalosporin an ti bi otic, was first launched by Takeda in Ja pan in 

1981. In 1983, Takeda launched Pansporin in the Phil ip pines and Thai land as Ceradolan, then in 1988 it 

was launched in Hong Kong, also as Ceradolan. 

In Sep tem ber 2008 Takeda filed a suit against Taiyo Yakuhin who man u fac tures Pansporin, de mand ing 

dam ages of Yen2.8 bil lion claim ing its qual ity con trol sys tem was de fi cient af ter it failed to re call all vi als 

(in which glass was found) from the market. 

Li cens ing: Pansporin was li censed to Ciba for world wide mar ket ing. Ciba (now part of Novartis, Swit zer - 

land) has launched it in a num ber of coun tries as Halospor, in clud ing Ger many, the Neth er lands and Ma - 

lay sia. Li censee Han Il launched it in South Ko rea in 1983. In 1989, it was ap proved for US mar ket ing as 

Ceradon, but has never been launched in North Amer ica and Takeda is not de vel op ing the oral form, 

Pansporin T (re fer to drug record) in the USA. 

Sales/An a lyst Com ment: With re ported sales of Yen8.4 bil lion in fis cal 2007 (end ing March 2008), 

Mor gan Stan ley an a lysts (Au gust 2008) fore cast a de cline in sales to Yen7.0 bil lion by the year to March 

2013. 

PANSPORIN T (cefotiam hexetil), an oral ver sion of the cephem an ti bi otic Pansporin, was launched in 

Ja pan in 1990. In 1993, it was launched in France by Takeda as Taketiam in part ner ship with Roussel 

Uclaf (now part of sanofi-aventis, France), which launched it as Texodil. Li censee Cheil launched it in 



1993 in South Ko rea as Brosporin. Takeda is not de vel op ing the prod uct in the US. In Oc to ber 2006, 

Takeda brought a le gal ac tion to re in state a US pat ent cov er ing meth ods for man u fac tur ing cephem 

compounds. 

TAKESULIN (cefsulodin), an in ject able cephalosporin an ti bi otic de vel oped in-house by Takeda, was first 

launched by li censee Ciba in France in 1980. It was launched in 1981 in Ja pan. Novartis and Takeda 

co-mar ket the prod uct in Ja pan and cer tain other mar kets out side North Amer ica, while in some mar kets, 

Novartis sells the prod uct in de pend ently. It has been filed in the US by TAP, Takeda’s joint ven ture with 

Abbott (USA), but has never been launched there, al though Abbott launched it as Cefmonil in Can ada in 

1986. The TAP joint ven ture con cluded in May 2008 and Takeda re ceived rights to this pro gram. Takeda 

mar kets the drug in France and has launched it in In do ne sia, Ma lay sia, the Phil ip pines and Thai land. In 

Ger many and Aus tria, the drug is mar keted by Takeda Pharma. Novartis now mar kets the prod uct in a 

num ber of Eu ro pean coun tries, as well as in Israel, Saudi Arabia and Thailand. 

TMR (vac cine, live, at ten u ated mea sles, ru bella) is a freeze-dried, live, at ten u ated mea sles and ru bella 

com bi na tion vac cine, launched in Ja pan in Jan u ary 2006 for the pre ven tion of mea sles and rubella. 

OTC Prod ucts 

Takeda’s main prod uct in the Con sumer Health busi ness is the Alinamin range of vi ta min and tonic prod - 

ucts. Other prod ucts in the di vi sion in clude cold rem e dies, con sti pa tion med i cines and vi ta min C prod - 

ucts. The Con sumer Healthcare busi ness ac counts for about 4.6% of Takeda’s rev e nues, but it posted a 

slight in crease in sales from Yen58.7 bil lion to Yen61.8 bil lion in the year to March 2008. 

Takeda pre sum ably still sees its Con sumer Health di vi sion as core to its con tin u ing busi ness, al though 

there was no men tion of it in the lat est five-year man age ment plan. How ever there are at pres ent no 

plans to di vest it as has hap pened with other non-phar ma ceu ti cal businesses. 

Ma jor prod ucts in clude: 

ACTAGE musculoskeletal prod ucts. Actage AN, a prod uct for musculoskeletal prob lems and for vi ta min 

B1 supplementation was launched in March 2003. 

ALINAMIN vi ta min and tonic prod ucts. Alinamin is Takeda’s best-sell ing OTC brand. The range in cludes 

Alinamin A25 (vi ta min B1 tab lets), Alinamin EX (a vi ta min E-for ti fied vi ta min B1, B6 and B12 com - 

pound), Alinamin V, a 50ml vi ta min B com plex health tonic drink, launched in 1987, Alinamin Dy - 

namic, a 100ml tonic drink, launched in 1996, and New Alinamin A, which con tains more vi ta min B6 

and B12 than the orig i nal prod uct, launched in 1999. In the year to March 31 2008, sales of Alinamin 

more than dou bled to Yen35 bil lion (from Yen14.6 bil lion) and for Alinamin Drink to Yen32 bil lion (from 

Yen12.1 bil lion the pre vi ous year) and pro jected by an a lysts at Mor gan Stan ley to drop and re main at 

Yen60 bil lion and Yen15 bil lion re spec tively from fis cal 2008 through 2012 (ending March 2013). 

BENZA (acetylsalicylic acid/ascor bic acid), a line of cough and cold treat ments, first launched in 1966. 

Prod ucts in clude Benza Ace and Benza De con ges tant. Benza AL Spray for rhi ni tis was launched in 

Ja pan in 1998. Benza Block Cough Syrup was launched in 1999. In 2003, Takeda an nounced ces sa - 

tion of pro duc tion and mar ket ing of some of its phenypropanolamine-con tain ing Benza prod ucts; no ta bly 

the cold rem edy Benza Block SP (ibuprofen/phenylpropanolamine). With drawal from the mar ket fol - 

lowed warn ings from the Jap a nese Health, Wel fare and La bor de part ment that 

phenypropanolamine-con tain ing prod ucts might be linked to ce re bral hem or rhagic ad verse ef fects. In 

the year to March 31 2008, sales of Benza in creased to Yen10 bil lion (from Yen7.7 bil lion the pre vi ous 

year) and pro jected by an a lysts at Mor gan Stan ley to drop and re main at Yen8.5 bil lion from fiscal 2008 

through 2012 (ending March 2013). 



BORRAGINOL, an antihemorrhoidal prod uct range, in clud ing Borraginol A and Borraginol M. 

FROMIN Ace, a vi ta min-for ti fied tonic. 

GROVIS, a med i cated hair tonic. 

HICEE (ascor bic acid/pantothenic acid), vi ta min C-based prod ucts. The range in cludes Hicee 1000, a 

gran u lated vi ta min C prod uct, Hicee B Mate, a vi ta min B/vi ta min C com bi na tion, Hicee-L chew able vi - 

ta min C tab lets and Hicee Pizea, a vi ta min E-for ti fied vitamin C preparation. 

MY TEAR eye care prod ucts. An oph thal mic for mu la tion of the anti-in flam ma tory panoprofen was 

launched in Oc to ber in Ja pan. The prod uct MyTear Eytect, de vel oped with Senju (Ja pan) is an OTC ver - 

sion of a pre scrip tion prod uct al ready mar keted as Niflan by Mitsubishi (Japan). 

NICORETTE smok ing ces sa tion chew ing gum. Takeda launched NICORETTE COOL MINT gum in De - 

cem ber 2005 and Nicorette Patch in July 2008. This launch helped the Nicorette range to gen er ate sales 

of Yen10 bil lion in the year to March 31 2008 (from Yen4.3 bil lion the pre vi ous year) and pro jected by an - 

a lysts at Mor gan Stan ley to drop and re main at Yen4.0 bil lion from fis cal 2008 through 2012 (end ing 

March 2013). 

PANVITAMIN HI, a mul ti vi ta min prep a ra tion with cal cium and mag ne sium. 

SCORBA DASH, (butenafine) an ath lete’s foot rem edy, launched in 2003 for the once-daily treat ment of 

ath lete’s foot in spray and cream for mu la tions. 

Scorba Ex, a se ries of antipruritic and antifungal prod ucts for ath lete’s foot and tinea launched in 2008. 

SHIN-BIOFERMIN, an in tes ti nal reg u la tor, based on a com bi na tion of lac tic acid and bac te ria, for in di - 

ges tion, con sti pa tion and flatulence. 

STANDBY, a liq uid gas tro in tes ti nal med i ca tion. 

TAKEDA ICHOYAKU 21, an ant acid, com bin ing syn thetic and herbal ac tive in gre di ents. 

TAKEDA KANPO BENPIYAKU, a herbal lax a tive. 

THAT’S BLOCK (cimetidine) ant acid pow der and tab lets, launched in 1997. The prod uct is sup plied by 

Sumitomo (Ja pan), and is also mar keted by Daiichi and Sumitomo. 

YOUR LIFE, a se ries of OTC nu tri tional sup ple ments and health food prod ucts, in clud ing mul ti vi ta mins, 

vi ta min C and cal cium test mar keted in 1997. Leiner Health Prod ucts (USA) spe cif i cally de vel oped the se - 

ries for the Jap a nese mar ket, in cooperation with Takeda. 



Research Pipeline for Takeda 

R&D Profile 

Compound Code Class Phase 

drug delivery system, modified 

release dexlansoprazole TAK 390MR A2B2 Approved 

febuxostat TMX 67, TEI 6720 M4A Approved 

alogliptin benzoate SYR 322 A10N1 Filed 

idebenone SNT MC17 N6D, N7X, M5X Filed 

panitumumab AMG 706 L1X3 Filed 

pioglitazone + metformin 

extended-release — A10K3 Filed 

asoprisnil J 867 G2X9 III 

azilsartan + pioglitazone — C9C III 

azilsartan medoxomil TAK 491 C9C III 

bis-aryl-sulphanyl amine LU AA21004 N6A9 III 

cetilistat ATL 962 A8A III 

ilaprazole IY 81149 A2B2 III 

motesanib AMG 706 L1X4 III 

pegylated erythropoietin 

receptor agonist AF 37702 B3X III 

repaglinide — A10B9 III 

resatorvid TAK 242 L4A, V3X III 

vedolizumab MLN 0002 A7E III 

venlafaxine WY 45030 N6A5, N5C, N7X III 

antirheumatic TAK 783 M1C II 

azilsartan TAK 536 C9C II 

bis-aryl-sulphanyl amine LU AA24530 N6A9 II 

ddp-iv inhibitor SYR 472 A10N1 II 

diabetic neuropathy therapy TAK 428 N7X II 

epa/dha agent TAK 085 C10A9 II 

epetirimod TAK 851, R 851 J5B II 

factor xa inhibitor TAK 442 B2C1 II 

G2 checkpoint abrogater CBP 501 L1X1 II 

GnRH analogue, Norwood 

Immunology/Takeda — L2A3 II 

insulin sensitizer TAK 379 A10X II 


lestaurtinib CEP 701 L1X4 II 

MAb, CCR2, Millennium MLN 1202 L4A, N7X, C6A II 

P38 MAP kinase Inhibitor TAK 715 M1C II 

PHN therapy TAK 583 N7X II 

tandutnib MLN 0518 L1X4 II 

advanced malignancies therapy MLN 4924 L1X9 I 



ARB for hypertension TAK 591 C9C I 

cancer therapy MLN 2238 L1X9 I 

CCR5 antagonist — J5C9 I 

conatumumab AMG 655 L1X3, T1G I 

ddp-iv inhibitor TAK 100 A10N1 I 

inflammatory disease therapy MLN 0415 A7E, R3X, N7X I 

inflammatory disease therapy MLN 3701 M1C I 

injectable gnrh modulator TAK 683 H4X, L1X9 I 



lh-rh receptor antagonist TAK 385 H1C3 I 

neuroregeneration enhancer TAK 065 N4A, N7D9 I 

oral her2 inhibitor TAK 285 L1X4 I 

oral sex hormone synthesis inhibitor TAK 700 L1X9 I 

potassium-competitive acid blocker (oral) TAK 438 A2B2 I 

prostate cancer therapy TAK 448 L1X9 I 

urinary incontinence therapy TAK 363, TRK 130 G4D I 

VEGFR and PDGFR inhibitor TAK 593 L1X4 I 

ANG receptor antagonist AMG 386 L1X9 Preclinical 

asthma and allergic rhinitis therapy MLN 6095 R3X Preclinical 

ceftaroline TAK 599, PPI 0903 J1D Preclinical 

COX inhibitor XEN 401 M1A1 Preclinical 

Crohn’s disease therapy MLN 3126 A7E Preclinical 

MAb, hepatocyte growth factor, Galaxy TAK 701, HuL 2G7 L1X3 Preclinical 

MAb, IGF-1, Amgen AMG 479 L1X3 Preclinical 

MAb, interleukin-1, Amgen AMG 108 M1C Preclinical 

MAb, interleukin-4/interleukin-13, Amgen AMG 317 R3X Preclinical 

SARM LGD 2226 G3B, M5B Preclinical 

vaccine, acellular pertussis, tetanus, 

diphtheria, poliovirus, Takeda TAK 361S J7B1 Preclinical 

Takeda is one of the six Jap a nese com pa nies with an an nual R&D bud get of around $1 bil lion, the spend - 

ing of which is crit i cally im por tant in or der to pri or i tize in vest ment in their pipe line. R&D at Takeda is fo - 

cused around four ar eas: on col ogy and urol ogy; life style dis eases, cen tral ner vous sys tem (CNS) and 

gas tro in tes ti nal (GI) dis or ders. The ac qui si tion of Mil len nium, giv ing ac cess to mar keted prod uct Velcade 

and 10 early stage mol e cules has been de scribed as the most sig nif i cant and stra te gi cally transformative 

deal in Takeda’s his tory, giv ing a large boost to its on col ogy fran chise. The ad di tion of Velcade may be 

Takeda’s lone bright spot as the pat ent ex pi ra tions of main stay prod ucts Actos and Prevacid near with lit - 

tle other than Velcade to sig nif i cantly fill the gap fol low ing un for tu nate de lays from missed PDUFU dates 

for both fol low-on prod ucts, Kapidex (TAK 390MR), a mod i fied re lease ver sion of an ac tive en an tio mer of 

Prevacid (lansoprazole) for acid re lated dis eases and the dipeptidyl peptidase IV (DPP-IV) in hib i tor 

alogliptin. Ex pected to be come Takeda’s two new main stay prod ucts, Kapidex was fi nally ap proved in 

Jan u ary 2009, mean ing it will be launched be fore the loss of pat ent pro tec tion for Prevacid in No vem ber. 

Ap proval of alogliptin is de layed un til June 2009 how ever, a de lay of eight months from the orig i nal date 

and it now lags well be hind Merck &Co’s Januvia (sitagliptin), which has be come the ‘gold stan dard’ for 

the DPP-IV in hib i tor class, with new prod ucts ex pected to show su pe ri or ity. An a lysts so far seem to be of 

the opin ion that alogliptin only of fers sim i lar safety and ef fi cacy to Januvia, al though the ex act in di ca tion 

Takeda seeks is not fully re vealed. Takeda does how ever have greater experience in diabetes, and that 

approval of a pill combining alogliptin with Actos is also expected in the second half of 2009. 

The ac qui si tion of Mil len nium also brought ex pan sion in the field of in flam ma tion with vedolizumab (MLN 

002), a hu man ized monoclonal an ti body that spe cif i cally binds with cell ad he sion mol e cule for in flam ma - 

tory bowel dis ease which Takeda in tends to file for ap proval in Ja pan, the US and Eu rope in 2011. Two 

phase III tri als were ini ti ated in Jan u ary 2009, as part of the GEM INI pro gram that will study vedolizumab 

in ul cer ative co li tis and Crohn’s dis ease, en roll ing 2,000 pa tients from 40 coun tries (in clu sion of Ja pan not 

yet de cided) with mod er ate-to-se vere dis ease, un re spon sive to stan dard ther a pies. Takeda hopes this 

will fur ther en hance its pres ence in the mar ket for gas tro in tes ti nal drugs which it has established with the 

PPI lansoprazole. 

The ac qui si tion of Amgen in Ja pan is a strong mes sage that Takeda will fully em bark on ad vanced phar - 

ma ceu ti cal de vel op ment in the fields of on col ogy and an ti body pharmaceuticals. Takeda Bio pres i dent re - 

vealed am bi tions to com mence clin i cal de vel op ment of the 10 pre clin i cal can di dates by 2010 and to file 

for ap proval of prod ucts gained from the in au gu ra tion of Amgen Ja pan. This started with Vectibix 

(panitumumab), a co lon can cer hu man monoclonal an ti body to the ep i the lial growth fac tor re cep tor 

(EGFR), which was filed for ap proval in June 2008 for colorectal can cer. A fil ing for motesanib, an 



antiangiogenic small mol e cule in phase III tri als in the USA, Eu rope and Ja pan in 2009, is planned by 

2010. Pa tient en rol ment in the MONET1 trial of motesanib in the treat ment of nonsmall cell lung can cer 

(NSCLC) was tem po rarily sus pended in No vem ber 2008 how ever, based on a higher early mor tal ity rate 

with motesanib. The trial’s in de pend ent Data Mon i tor ing Com mit tee (DMC) rec om mended im me di ate 


pected hemoptysis rate in these pa tients but not in pa tients with non-squamous NSCLC and in Feb ru ary 

2009, the DMC recommended the resumption of enrollment of patients with non-squamous NCSLC. 

Takeda says its ag gres sive al li ance pol icy aims at a wide range of tech nol o gies and prod ucts and the com - 

pany has said it will ac quire any new tech nol ogy and prod uct nec es sary for the com pany to com pete on 

the global mar ket with top man age ment in volved in all deals of any size. 2008 was a par tic u larly ac tive 

year as the com pany worked to tackle its long-stand ing chal lenges, in clud ing es tab lish ing and strength - 

en ing its pres ence in the global mar ket, en hanc ing its pres ence in on col ogy in ad di tion to sugar me tab o - 

lism and car dio vas cu lar med i cine, as well as in creas ing pro duc tiv ity of R&D. In May 2008, Takeda en tered 

a $1 bil lion li cens ing deal with Alynlam gain ing ac cess to its RNA in ter fer ence tech nol ogy in on col ogy and 

met a bolic dis ease and be com ing Alnylam’s stra te gic part ner for RNAi ther a peu tics. Un der stand ing RNAi 

en ables the ‘switch ing on/off’ of genes and gene si lenc ing, lead ing to the cre ation of a po ten tial new class 

of RNAi ther a peu tics. Takeda is so far Ja pan’s only com pany working in this area and the deal was 

selected as In Vivo Blog’s ‘deal of the year’ for 2008. 

Takeda has been fill ing its on col ogy pipe line through li cens ing deals, in clud ing one in April 2008 with Cell 

Genesys for the pros tate can cer immunotherapy GVAX, al though Takeda ter mi nated de vel op ment in De - 

cem ber 2008 with all com mer cial rights to be re turned to Cell Genesys. As part of the li cense agree ment 

with Amgen in Feb ru ary 2008, Takeda has ac quired rights to de velop and mar ket al most all of Amgen’s 

pipe line (13 prod ucts), ex clud ing Amgen’s main prod ucts which have al ready been li censed to Kirin and 

Daiichi Sankyo, in ad di tion to Amgen’s hu man re sources spe cial iz ing in the de vel op ment of 

biopharmaceuticals. Takeda will pay up to $837 mil lion in upfront and de vel op ment mile stone pay ments. 

The most ad vanced prod uct was Vectibix (panitumumab) for colorectal can cer, now ap proved and gen er - 

at ing block buster sales. The only other prod uct at a late stage of de vel op ment is motesanib (AMG 706) 

for can cer, and said to be one of the main driv ers of the deal for Takeda. Other prod ucts li censed in clude a 

num ber for can cer: AMG 386, AMG 479 and AMG 655; as well as AMG 108 for rheu ma toid ar thri tis and 

AMG 317 for asthma. The li censed prod ucts will strengthen Takeda’s pri or ity fields of can cer and uro log i - 

cal dis eases (12 pro jects un der way in clud ing line extensions) as well as CNS and bone joint disease (11 

projects underway). 

Com pared to most Jap a nese com pa nies, Takeda was pre vi ously rel a tively un-re li ant on in-li cens ing for 

its rev e nues. With three of Takeda’s four block bust ers go ing off-pat ent be tween 2009 and 2012 

(lansoprazole in 2009, pioglitazone in 2011 and candesartan in 2012) how ever, Takeda plans to in vest 

15% of its an nual R&D bud get to ob tain li cens ing can di dates from out side. Takeda in tends to li cense-in 

prod ucts for hyperlipidemia, ath ero scle ro sis, can cer, schizo phre nia, de pres sion, and con sti pa tion-type 

in flam ma tory bowel syn dromes. 



Alimentary Tract and Metabolism Agents 

drug delivery system, modified release 

dexlansoprazole TAK 390MR A2B2 Approved 

alogliptin benzoate SYR 322 A10N1 Filed 

pioglitazone + metformin extendedrelease 

— A10K3 Filed 

cetilistat ATL 962 A8A III 

ilaprazole IY 81149 A2B2 III 

repaglinide — A10B9 III 

vedolizumab MLN 0002 A7E III 

ddp-iv inhibitor SYR 472 A10N1 II 



ddp-iv inhibitor TAK 100 A10N1 I 

inflammatory disease therapy MLN 0415 A7E, R3X, N7X I 

potassium-competitive acid blocker (oral) TAK 438 A2B2 I 

Crohn’s disease therapy MLN 3126 A7E Preclinical 

TAK 390MR is a mod i fied-re lease for mu la tion of an en an tio mer of the pro ton pump in hib i tor 

dexlansoprazole, for the treat ment of gastroenterological acid-re lated dis or ders. In late Jan u ary 2009, 

one year af ter fil ing, Takeda an nounced that the FDA ap proved TAK 390MR for the treat ment of acid-re - 

lated dis eases and treat ment and main te nance of pa tients with ero sive esophagitis and non-ero sive re - 

flux dis ease. Kapidex is po si tioned as a suc ces sor to Prevacid which goes off pat ent in No vem ber 2009. 

The TAP jv concluded in May 2008. 

The prod uct en tered phase II tri als in Ja pan in 2007 and in May 2008, fa vor able late-stage trial re sults 

were re ported show ing that it was more ef fec tive than Prevacid in heal ing in flam ma tion of the esoph a - 

gus; these tri als were ongoing in 2009. 

Li cens ing: The com pound is li censed to TAP for de vel op ment in North Amer ica and if suc cess ful, could 

cush ion the ex pected huge loss to the com pany’s prof its when Prevacid’s pat ent ex pires in 2009. The new 

prod uct will com pete with AstraZeneca’s Nexium, the suc ces sor to Prilosec. 

Clin i cal Data: The NDA fil ing in Jan u ary 2008 was based on stud ies which eval u ated over 6000 sub jects 

in more than 20 coun tries. In Au gust 2005, TAP ini ti ated phase III tri als to eval u ate TAK 390MR in more 

than 5,000 pa tients with gastroenterological acid-re lated dis or ders in the USA. The FDA al lowed phase II 

tri als to be skipped as the mo lec u lar struc ture of the mol e cules are a mir ror im age (enantiomer) of 

Prevacid. 

Sales/An a lyst Com ment: An a lysts at Mor gan Stan ley writ ing in Au gust 2008 fore cast sales of Yen21 

bil lion in the next fis cal (end ing March 2009) ris ing to Yen210 bil lion by the year end ing March 2013. 

SYR 322, an oral dipeptidyl peptidase IV (DPP-IV) in hib i tor was filed for US ap proval in De cem ber 2007 

for the treat ment of type II di a be tes, two years af ter en ter ing a global (mainly US and Ja pan) phase III 

trial which com menced just four years fol low ing first lab tests; Takeda has not re vealed the ex act in di ca - 

tions sought for the prod uct. Alogliptin is ex pected to be come a new main stay for Takeda and US ap - 

proval is ex pected in June 2009, a de lay of eight months from the orig i nal date al though no is sues have 

been raised and this is due to con straints within the FDA. In Sep tem ber 2008, Takeda filed for ap proval of 

alogliptin in Ja pan. Al though no phase III stud ies have been con ducted in Ja pan, the fil ing is based on re - 

sults of phase III and ear lier stud ies abroad. Re sults of these over all show that alogliptin sig nif i cantly re - 

duces HbA1c safely and with good tolerability. Phase III trials were underway in Europe in 2009. 

The agent was gen er ated by Syrxx (now part of Takeda) from a pro gram ini ti ated in 2002, to dis cover 

DPP-IV in hib i tors, af ter de ter mi na tion of the struc ture of DPP-IV. DPP-IV is an en zyme which breaks 



down hor mone glucagon-like pep tide 1 and its in hi bi tion re sults in in creased GLP-1 lev els which stim u late 

pan cre atic in su lin pro duc tion and sup presses glucagon pro duc tion and may help to re store beta is let cell 

func tion and lost in su lin pro duc tion. This new class is ex pected to be ther a peu ti cally im por tant due to a 

ben e fi cial side ef fect pro file over ex ist ing therapies which result in weight gain and edema. 

Li cens ing: In 2003, Syrrx signed an agree ment with PPD (USA) to jointly de velop DPP-IV in hib i tors. In 

2005, Takeda ac quired Syrrx (to form Takeda San Diego), gain ing SYR 322 in the pro cess. In July 2005, 

Takeda and PPD ter mi nated the pre vi ous col lab o ra tion, and signed an agree ment grant ing Takeda de vel - 

op ment and mar ket ing rights to DPP-IV in hib i tors, in clud ing SYR 322. PPD is now the sole pro vider of 

phase II/III de vel op ment ser vices to Takeda in the US and Europe. 

Clin i cal Data: The ap proval sub mis sion was based on re sults from six phase III tri als in volv ing over 

2000 pa tients. Dur ing these stud ies, alogliptin was ad min is tered as a once-daily monotherapy ad junct to 

diet and ex er cise and as add-on ther apy to other antidiabetic agents. Re sults showed that 

alogliptin-treated pa tients had sta tis ti cally sig nif i cant re duc tions in he mo glo bin A1c (re flect ing av er age 

blood glu cose con cen tra tions over the pre vi ous two to three months). The agent was gen er ally well tol er - 

ated and weight-neu tral. No in crease in hypoglycemia was observed compared with placebo. 

Lifecycle Man age ment: Takeda has been con duct ing phase III tri als of pioglitazone in com bi na tion 

with the DPP-4 in hib i tor SYR-322 in the US and Eu rope and in Sep tem ber 2008 filed an NDA for a 

fixed-dose com bi na tion drug. Ap proval is ex pected no ear lier than mid-2009. The fil ing was sup ported by 

data from two phase III stud ies in volv ing 2,000 pa tients world wide who did not achieve glycemic tar gets 

with diet and ex er cise or metformin alone. The com bi na tion was re ported to sig nif i cantly im prove 

glycemic con trol as well as pa ram e ters re lated to beta cell func tion/in su lin re sis tance and be gen er ally 

well tol er ated. This com bi na tion was un der go ing phase III evaluation in Europe and phase I in Japan in 

2009 

Com pe ti tion: If ap proved, SYR 322 will be the sec ond DPP-IV in hib i tor af ter Merck & Co’s Januvia 

(sitagliptin) which was the first to reach the US mar ket (in Oc to ber 2006) and is now the ‘gold stan dard’ 

for this class fol low ing a strong ini tial launch; it is now also avail able in the EU and in De cem ber 2007 be - 

came the first to be filed for ap proval in Ja pan. In or der for newer DPP-IVs to com pete ef fec tively, they 

must as a min i mum be as good as Januvia in terms of ef fi cacy and safety. Ad di tion ally, while it may be 

pos si ble to have a sim i lar pro file to Januvia, it will not be easy to dem on strate su pe ri or ity. By the 12 

months to Sep tem ber 2008, Januvia had al ready be come the world’s sec ond-ranked oral antidiabetic 

(A10B class), ac cord ing to IMS, with 8.7% mar ket share. In first po si tion was Takeda’s glitazone Actos, 

with a 28.1% share and 9% sales growth, with GSK’s Avandia down 52% to third place with 8.1% share 

af ter a num ber of ques tions over the prod uct’s safety. There is a chance that the safety is sues for Avandia 

and other antidiabetics could ben e fit Januvia, as the FDA is likely to re quire large, long-term safety stud - 

ies, es pe cially to mon i tor car dio vas cu lar risks, thus pos si bly de lay ing the ar rival of new com pet i tors. An 

FDA ad vi sory panel voted in fa vor of such a move in July 2008. In April 2008, both glitazones were linked 

to an in creased risk of bone frac tures. While many phy si cians are likely to stick with tried-and-tested 

metformin, some may opt to pre scribe Januvia in stead of a glitazone in pa tients who re quire fur ther blood 

sugar con trol. Al though Takeda will face stiff com pe ti tion, the prod uct will en force Takeda’s antidiabetic 

strong hold with Actos with and with out metformin, acarbose and mitiglinide. An a lysts so far seem to be 

of the opin ion that alogliptin only of fers sim i lar safety and ef fi cacy to Januvia, though ac knowl edge that 

Takeda does have greater ex pe ri ence in di a be tes, and is also await ing ap proval of a pill com bin ing 

alogliptin with its lead ing glitazone, Actos (pioglitazone), expected in the second half of 2009. 

Januvia’s main com pet i tor is ex pected to be Novartis’ Galvus (vildagliptin), which was launched in June 

2007 in Brazil and Mex ico, and was ap proved in all 27 EU mem ber states as well as Nor way and Ice land in 

Sep tem ber 2007. How ever, the EU launch is likely to be de layed un til Novartis has re solved the liver 

safety prob lems as so ci ated with high doses of the drug. In No vem ber 2007, Novartis pro vided the Eu ro - 

pean reg u la tors with data that showed liver en zyme el e va tions were less fre quent in pa tients tak ing the 



once-daily or twice-daily 50mg doses com pared with the 100mg once-daily dose. The EMEA ap proved 

50mg once daily in com bi na tion with a sulphonylurea, or 50mg twice daily in com bi na tion with metformin 

or a thiazolidinedione, in Feb ru ary 2008: the pre vi ously ap proved 100mg once-daily dose of vildagliptin 

will not be avail able. In No vem ber 2007, the EMEA cleared Eucreas, a sin gle-tab let com bi na tion of 

Galvus and metformin, and its Eu ro pean roll-out com menced in March 2008. US ap proval has also been 

af fected by skin tox ic ity wor ries. Galvus was filed with the FDA in March 2006, and had its re view pe riod 

ex tended by the FDA by three months from No vem ber 2006 af ter clin i cal data were sub mit ted to sup port 

the pro posed dos ing and in di ca tions as well as com ple ment ear lier data on the risk:ben e fit pro file. Then in 

Feb ru ary 2007 the FDA is sued an ‘ap prov able’ let ter for the prod uct and re quested ad di tional data, in - 

clud ing a clin i cal study in pa tients with re nal im pair ment. This has de layed the de vel op ment of Galvus in 

the US for at least two years. Novartis is now con duct ing safety stud ies, but a resubmission for US reg u la - 

tory ap proval is not ex pected be fore 2010, and the Swiss gi ant’s CEO hinted in Jan u ary 2008 that it may 

not seek to refile Galvus with the FDA at all. Galvus was filed for Japanese approval in April 2008. 

Januvia may have an ad van tage over Galvus in terms of half-life and the po ten tial for true once-a-day 

dos ing. Galvus looks like it low ers blood sugar better than Januvia and an a lysts are pro ject ing an nual 

sales peak sales of more than $2 bil lion for Galvus. The per cep tion is that many di a be tes spe cial ists are 

ex cited about the po ten tial of these agents, but are wait ing to see more data on their risk:ben e fit pro file. 

Con cerns re main that these agents could be af fect ing sub strates other than DPP-IV, ex ert ing their met a - 

bolic ef fects in sub strates with the po ten tial for ad verse ef fects. The com mer cial po ten tial of DPP-IV in hib - 

i tors ob vi ously ex ceeds that of the GLP-1 ag o nist due to their oral avail abil ity, un less the lat ter are 

suc cess fully de vel oped in a form that re quires in fre quent in jec tion. Ul ti mately, the value of both ap - 

proaches will hinge on how the is sue of beta cell func tional im prove ment and pres er va tion plays out. Re - 

nal pro file could be one point of dif fer en ti a tion be tween Januvia and Galvus and ac cord ing to Novartis, 

Galvus has a dif fer ent re nal pro file than Januvia. Januvia is ex creted about 75% through the kidney. 

Galvus on the other hand, is only slightly excreted by the kidney, about 23%. 

Be sides Merck and Novartis, a num ber of other com pa nies are de vel op ing DPP-IV in hib i tors. Bris - 

tol-Myers Squibb’s Onglyza (saxagliptin) com menced phase III tri als in 2006, and is be ing co-de vel oped 

with AstraZeneca; it was filed for both US and EU ap proval in June 2008. A large num ber of other com pa - 

nies, in clud ing Roche and Novo Nordisk, have pre clin i cal DPP-IV in hib i tor can di dates. Probiodrug’s (Ger - 

many) P93/01 (li censed to Merck and OSI Pharmaceuticals, USA) and Mitsubishi Tanabe Pharma’s 

(Ja pan) TA 6666 (li censed to GlaxoSmithKline) are both in phase II. A large num ber of other com pa nies, 

in clud ing Roche (Swit zer land) and Novo Nordisk (Den mark), have DPP-IV in hib i tors candidates in early 

stages of development. 

The more fa vor able side ef fect pro file of the DPP-IV agents rel a tive to sulphonylureas and glitazones 

means that there is po ten tial for these drugs to have strong up take as sec ond line, add-on agents in Type 

II di a be tes pa tients who are not ad e quately con trolled on metformin alone. The fact that the DPP-IVs 

have much less in va sive oral dos ing, to gether with their lack of weight gain and the po ten tial to im prove 

beta cell func tion, should po si tion them for broader ap peal (un like Amylin and Lilly’s Byetta (exenatide), 

which is gen er ally pre scribed by en do cri nol o gists and spe cial ists). There is po ten tial for these oral 

antidiabetics to re place older sulphonylureas at a sig nif i cantly higher price point. How ever the ad van - 

tages must be bal anced against the com plex ity of the DPP-IV path way and the long-term na ture of the 

head-to-head tri als that will be re quired to dem on strate any favorable effects on beta cell function in 

humans. 

Byetta is an incretin mi metic (GLP-1 ag o nist) and syn thetic form of exendin 4, a pep tide iso lated from the 

sal i vary se cre tions of the Gila mon ster liz ard. It is in di cated as an ad junc tive ther apy to help im prove 

blood sugar con trol in Type II di a bet ics not ad e quately con trolled by metformin and/or a sulphonylurea. 

Its sales have per haps not achieved the lev els once fore cast ($650 mil lion in 2007), de spite Lilly’s ex per - 

tise in the di a be tes field. In April 2008, one an a lyst re ported that Januvia was tak ing sales from Byetta, 

partly as it is ap proved as a stand-alone treat ment, and also be cause it is an oral, once-daily drug, 



whereas Byetta needs to be in jected twice a day — though a once-weekly in ject able form is also in 

late-stage de vel op ment. Byetta suf fered a fur ther set back in Au gust 2008, when it was as so ci ated with a 

small num ber of deaths from pan cre ati tis. At the EASD meet ing in Rome the fol low ing month, how ever, 

Lilly and Amylin pre sented data from a four-week study in 61 pa tients sug gest ing that Byetta re duced 

glu cose lev els more than Januvia (by 112mg/dL, ver sus 37mg/dL two hours af ter a meal), with pa tients 

us ing their body’s in su lin more ef fec tively. It was the first head-to-head trial of the two prod ucts. Novo 

Nordisk filed its GLP-1 prod uct, liraglutide, for FDA and EU ap proval in May 2008, and is working with 

Emisphere on the development of an oral version 

Sales/An a lyst Com ment: Mor gan Stan ley an a lysts (Au gust 2008) fore cast a first year sales of Yen42 

bil lion in the year to March 2010, ris ing to Yen187.5 bil lion by the year to March 2013. 

ACTOPLUS MET XR (pioglitazone + metformin ex tended-re lease), con sist ing of Andrx’s ex tended-re - 

lease for mu la tion of the biguanide metformin (Fortamet) and Takeda’s in su lin sensitizer pioglitazone 

(Actos) is be ing co-de vel oped by Takeda and Andrx for the treat ment of type II di a be tes. Takeda filed for 

ap proval of the prod uct in the USA dur ing March 2006 and in Eu rope in Oc to ber 2008; it will be mar keted 

as Competact Pro longed-Re lease Tab let. 

CETILISTAT (ATL 962) is a prod uct be ing de vel oped for the treat ment of obe sity and as so ci ated con di - 

tions, such as Type 2 di a be tes. It was li censed in from Alizyme (UK). In De cem ber 2008, Takeda com - 

menced phase III tri als of cetilistat for obe sity; de tails of this trial, or re sults of the phase II (pla cebo 

con trolled) study in obese pa tients with di a be tes and dyslipidemia have not yet been disclosed. 

Li cens ing: In 2003, Takeda gained an op tion from Alizyme to de velop, man u fac ture and mar ket the 

prod uct in Ja pan. In 2004, Takeda ex er cised its rights to a li cense to de velop cetilistat in Ja pan on the ba - 

sis of re sults from a phase IIb study. It now has an ex clu sive li cense to de velop, man u fac ture, and mar ket 

cetilistat in Ja pan for the treat ment of obe sity and as so ci ated con di tions, such as Type 2 di a be tes. In 

2006, upon com mence ment of a phase II trial, Alizyme re ceived a $2 mil lion milestone payment from 

Takeda. 

Clin i cal Data: In Jan u ary 2006, Takeda re ported that phase I tri als had com pleted and that it had ini ti - 

ated a ran dom ized, pla cebo-con trolled, dou ble-blind, par al lel group, dose-rang ing 450-pa tient (BMI of at 

least 25; over seas tri als tar get 30+) phase II trial in Ja pan, to eval u ate cetilistat in the treat ment of obe - 

sity and re lated dis eases such as Type 2 diabetes. 

The re sults of phase IIb tri als in Eu rope (look ing at 612 obese di a betic pa tients), an nounced in De cem ber 

2005, di rectly com pared the prod uct with Roche’s (Swit zer land) Xenical (orlistat) show ing sim i lar ef fi cacy 

with a marked re duc tion in side ef fects, al though a dif fer ent mech a nism of ac tion has not yet been 

revealed. 

Ac cord ing to Alizyme (UK), pre lim i nary phase IIb re sults sug gest that over a three-month pe riod, weight 

loss is con sis tent with “other ap proved obe sity drugs of the same class”. The drug was well tol er ated, was 

as so ci ated with im prove ments in blood lev els of LDL, HDL and cho les terol, and in duced com pa ra ble 

weight loss at the three doses tested. Alizyme re port that the prod uct has 90% fewer gas tro in tes ti nal 

events than Xenical. 

Ac cord ing to Takeda, phase IIb tri als in volv ing 372 clin i cally obese pa tients in five Eu ro pean coun tries 

met their pri mary end points of weight loss. The drug pro duced sta tis ti cally-sig nif i cant re duc tion in weight 

at all doses com pared with pla cebo. The agent dem on strated ef fi cacy com pa ra ble to other ap proved obe - 

sity drugs of the same class, with no safety or tolerability issues. 

Com pe ti tion: If ap proved, ATL 962 will com pete with Abbott’s (USA) Meridia (sibutramine) which was 

fi nally filed for ap proval in Ja pan in De cem ber 2007 with Eisai fol low ing a need to re peat clin i cal work and 

was await ing ap proval in 2009. Obe sity drugs have faced hur dles in Ja pan how ever, as Chugai de cided in 



April 2005 not to de velop Xenical af ter com plet ing phase II tri als, cit ing a need for ad di tional tri als un der 

lo cal guide lines. An a lysts at West LN Pan mure be lieve that the pos i tive side ef fect pro file and low cost of 

the prod uct should make the prod uct com pet i tive. Clin i cal re sults so far in di cate that cetilistat is better 

tol er ated than Xenical. Ac cord ing to IMS, the only antiobesity prod uct mar keted in Ja pan in the year end - 

ing Sep tem ber 2008 is an am phet amine type drug Teronac (mazindol), available in Japan since 1992 

and marketed by Novartis. 

ILAPRAZOLE is a pro ton pump in hib i tor. In Sep tem ber 2005, the TAP joint ven ture be tween Takeda and 

Abbott ac quired world wide rights out side South Ko rea and China. The TAP jv was con cluded in May 2008 

and Takeda will re tain this prod uct. Phase III tri als are on go ing in var i ous Asian coun tries, and phase II 

tri als are re ported in the US and Canada. 

Orig i na tor Il Yang (South Ko rea) has launched the prod uct China in May 2008. 

Li cens ing: Il Yang has li censed-out Chi nese rights to Livzon (China). 

NOVONORM/PRANDIN (repaglinide) is an oral agent for the treat ment of non-in su lin de pend ent di a - 

be tes (Type 2). Repaglinide was orig i nally de vel oped by Boehringer Ingelheim (Ger many) and li censed 

out to Novo Nordisk (Den mark), which has launched it in a num ber of mar kets world wide. In 1999, Novo 

Nordisk and Takeda agreed to co-mar ket repaglinide in Ja pan. Repaglinide has been launched in the USA, 

the EU and var i ous other mar kets. Repaglinide was re ported to be in phase III tri als in Ja pan with 

Dainippon Sumitomo who signed an agree ment with Novo Nordisk in 2004. 

VEDOLIZUMAB (MLN 002), a hu man ized monoclonal an ti body that in hib its the in ter ac tion be tween the 

alpha4beta7 integrin on lym pho cytes and the mucosal adressin mol e cule, MAdCAM-1, which is pre dom i - 

nant on mucosal tis sue in the gut, is be ing de vel oped as an in ject able treat ment for ul cer ative co li tis and 

Crohn’s dis ease. Two phase III tri als were ini ti ated in Jan u ary 2009, as part of the GEM INI pro gram that 

will study vedolizumab in ul cer ative co li tis and Crohn’s dis ease, en roll ing 2,000 pa tients from 40 coun - 

tries (in clu sion of Ja pan not yet de cided) with mod er ate-to-se vere dis ease, un re spon sive to stan dard 

ther a pies. The tri als will each con sist of a six-week in duc tion phase fol lowed by 46 weeks of main te nance 

ther apy with vedolizumab iv in fu sion. Pa tients will be given the op por tu nity to con tinue treat ment for up 

to 100 weeks as part of a fol low-up study eval u at ing the safety and ef fi cacy of the agent. Takeda in tends 

to file for ap proval in Ja pan, the US and Eu rope in 2011, and hopes this will fur ther en hance its pres ence 

in the market for GI drugs which it has established with the PPI lansoprazole. 

SYR 472, an orally ad min is tered dipeptidyl peptidase IV (DDP-IV) in hib i tor, as a po ten tial treat ment for 

type II di a be tes. The com pound was in phase II de vel op ment in the USA and the EU and phase I in Japan 

in 2009. 

TAK 379, an in su lin sensitizer was re ported to be in phase II tri als with Takeda in the US and Eu rope and 

phase I in Ja pan for di a be tes mellitus in 2009. 

TAK 875, an oral glu cose-de pend ent in su lin secretagogue, for the treat ment of di a be tes was re ported to 

be in phase II tri als with Takeda in Ja pan for di a be tes in 2009. 

TAK 100, an orally ad min is tered dipeptidyl peptidase IV (DDP-IV) in hib i tor, as a po ten tial treat ment for 

type II di a be tes, was re ported to be in phase I de vel op ment in 2009. 

MLN 0415, is an oral small mol e cule in hib i tor of IKK2, with po ten tial ap pli ca tion in the treat ment of in - 

flam ma tory dis eases, in clud ing rheu ma toid ar thri tis, mul ti ple scle ro sis, chronic ob struc tive pul mo nary 

dis ease (COPD) and in flam ma tory bowel dis ease. Phase I eval u a tion was un der way with Millennium (now 

Takeda) in 2009. 



TAK 438, an oral po tas sium-com pet i tive acid blocker was in phase I tri als with Takeda in 2009 for treat - 

ment of acid re lated dis ease in clud ing GERD, pep tic ulcer. 

MLN 3126, a chemokine re cep tor 9 (CCR9) an tag o nist, for the treat ment of Crohn’s dis ease was in pre - 

clin i cal stud ies with Mil len nium (now Takeda) in 2008. 

Antineoplastics/Immunomodulating Agents 

panitumumab AMG 706 L1X3 Filed 

motesanib AMG 706 L1X4 III 

resatorvid TAK 242 L4A, V3X III 

G2 checkpoint abrogater CBP 501 L1X1 II 

GnRH analogue, Norwood Immunology/ 

Takeda — L2A3 II 

lestaurtinib CEP 701 L1X4 II 

MAb, CCR2, Millennium MLN 1202 L4A, N7X, C6A II 

tandutnib MLN 0518 L1X4 II 




cancer therapy MLN 2238 L1X9 I 

conatumumab AMG 655 L1X3, T1G I 

oral her2 inhibitor TAK 285 L1X4 I 

oral sex hormone synthesis inhibitor TAK 700 L1X9 I 

prostate cancer therapy TAK 448 L1X9 I 

VEGFR and PDGFR inhibitor TAK 593 L1X4 I 

ANG receptor antagonist AMG 386 L1X9 Preclinical 

MAb, hepatocyte growth factor, Galaxy TAK 701, HuL 2G7 L1X3 Preclinical 

MAb, IGF-1, Amgen AMG 479 L1X3 Preclinical 

VECTIBIX (panitumumab) is a XenoMouse-de rived fully hu man IgG2kappa monoclonal an ti body 

tar geted to epi der mal growth fac tor is a po ten tial ther a peu tic for EGF-de pend ent can cers. Vectibix was 

co-de vel oped by Abgenix (USA, later ac quired by Amgen) and Amgen. It was launched in the USA in Oc - 

to ber 2006 for the sec ond-line treat ment of pa tients with epi der mal growth fac tor re cep tor ex press ing 

met a static colorectal can cer af ter dis ease pro gres sion on, or fol low ing, che mo ther apy. Out side the US, 

mar ket ing ap pli ca tions have been sub mit ted in Eu rope, Can ada, Aus tra lia, and Swit zer land. In May 

2007, the CHMP of the EU reg u la tory agency adopted a neg a tive opin ion for panitumumab for the treat - 

ment of met a static colorectal can cer in pa tients who have failed che mo ther apy. Amgen re quested a 

re-ex am i na tion of the opin ion and in De cem ber 2007 the EMEA is sued a con di tional mar ket ing au tho ri za - 

tion of panitumumab. The agency rec om mended the drug only for pa tients whose tu mors do not have a 

mu ta tion of KRAS — a gene that can stim u late can cer if mu tated. Amgen has launched a screen ing test to 

ver ify non-mu tated KRAS ex pres sion. Sub se quent launches of Vectibix for colorectal can cer were re - 

ported to have taken place through out Eu rope and other coun tries in clud ing the UK, Ire land, Ger many, 

Fin land, Aus tria, Swe den and the Slo vak Re pub lic as well as South Ko rea and France in 2008 in pa tients 

with metastatic colorectal cancer expressing the epidermal growth factor receptor (EGFR) and wild type 

KRAS gene. 

In June 2008, Takeda filed a sub mis sion for ap proval in Ja pan for panitumumab in colorectal can cer. This 

was the first fil ing to be made by Takeda through the Takeda Bio De vel op ment Cen tre, the re named and 

for merly wholly-owned Jap a nese sub sid iary of Amgen ac quired as part of an al li ance in February 2008. 

Phase III tri als were un der way for panitumumab in com bi na tion with che mo ther apy as first and sec ond 

line ther apy met a static colorectal and in head and neck as well in 2008/9 and will en roll 20-30 pa tients 

from Ja pan. Fur ther re sults are ex pected in late 2009 and fil ing within three years. Ad di tion ally, phase II 

tri als were in ves ti gat ing panitumumab in lo cally ad vanced head and neck cancer in 2008. 



The epi der mal growth fac tor re cep tor is over-ex pressed in a va ri ety of can cers in clud ing lung, breast, 

pan cre atic, blad der, pros tate, colorectal, kid ney, head and neck cancers. 

Li cens ing: Amgen and Takeda an nounced in Feb ru ary 2008 that they have signed an agree ment un der 

which Takeda will de velop and com mer cial ize in Ja pan up to 13 of Amgen’s early- to mid-stage clin i cal 

can di dates. The al li ance in cludes Amgen’s Vectibix (panitumumab), motesanib (AMG 706) and other 

ther a pies for can cer, in flam ma tion and neu rol ogy/pain. With the ex cep tion of motesanib, all mol e cules 

in cluded in the part ner ship are biologics. Amgen is en ti tled to an upfront cash pay ment of $200m, up to 

$340m in world wide de vel op ment costs, $362m in suc cess-based mile stone pay ments and dou ble-digit 

roy al ties on sales in Ja pan. Takeda will be come Amgen’s world wide part ner for motesanib, and will pay 

Amgen $100m upfront, $175m in suc cess-based mile stones for the first two in di ca tions and dou ble-digit 

roy al ties on sales in Ja pan. Takeda will pay 60% of on go ing clin i cal de vel op ment ex penses out side Ja pan 

and share po ten tial prof its out side Ja pan on a 50/50 ba sis. Amgen re tains cer tain co-pro mo tion rights in 

Ja pan on all pro grams. In con nec tion with these agree ments, Takeda ac quired Amgen’s sub sid iary in Ja - 

pan, Amgen KK and all shares of Amgen KK were trans ferred to Takeda dur ing 2008 and consequently, 

Takeda has exclusive development and commercialization rights in Japan. 

Clin i cal Data: Anal y sis of re sults in re la tion to biomarker KRAS in 2007 showed that Vectibix was in ef - 

fec tive in the 40% of met a static colorectal can cer pa tients who har bor a mu tated KRAS onco gene where 

this is al ways ‘turned on’ ir re spec tive of whether EGFR has been ac ti vated or ther a peu ti cally in hib ited. 

KRAS is part of the RAS fam ily of pro teins, long im pli cated in can cer and just down stream of the EGFR re - 

cep tor. This there fore in volves iden ti fy ing subpopulations within a larger in di ca tion (e.g. breast or 

colorectal) who will or will not respond to specifically targeted therapy. 

Amgen is con duct ing a phase III PRIME trial in 1,200 pa tients that com pares first line treat ment FOLFOX 

che mo ther apy with and with out Vectibix ef fects while a sec ond rial in 1,200 pa tients ex plores FOLRIEI 

(irinotecan-based) che mo ther apy with and with out Vectabix as sec ond line ther apy. Both tri als look at 

pro gres sion free sur vival (PFS) and over all survival (OS). 

In 2008, the most com mon side ef fect re ported from in terim anal y sis of on go ing colorectal tri als in 601 

pa tients was re ported to be skin rash, which oc curred in over half of the group com pared with 11% on the 

che mo ther apy group. 

In 2005, Amgen and Abgenix re ported re sults from a piv otal phase III trial of panitumumab in pa tients 

with met a static colorectal can cer who had failed stan dard che mo ther apy, in clud ing oxaliplatin and 

irinotecan. The study, in volv ing 463 pa tients at sites in Eu rope, Aus tra lia and Can ada, achieved its pri - 

mary end point of im prov ing pro gres sion-free sur vival in this pa tient pop u la tion; pa tients who re ceived 

panitumumab ev ery two weeks showed a 46% de crease in tu mor pro gres sion rate ver sus those who re - 

ceived best sup port ive care alone. This re sult ex ceeded the pre-spec i fied mea sure of pro gres sion-free 

sur vival that the trial was de signed to dem on strate (a 33% de crease in tu mor pro gres sion rate in 

panitumumab-treated pa tients ver sus pa tients re ceiv ing best sup port ive care). The study also met its 

sec ond ary end point of ob jec tive re sponse rate, as as sessed by cen tral ra di ol ogy re view. Ini tial safety 

data showed that ad verse events ob served were con sis tent with pre vi ous tri als of panitumumab, with the 

most com mon side ef fects be ing acneiform rash, fa tigue, nau sea and mild di ar rhea. No human 

anti-human (HAHA) or anti-panitumumab antibody formation was observed. 

Up dated re sults from an on go ing phase II study of panitumumab was pre sented in May 2005 at the 41st 

ASCO meet ing. The re sults dem on strate that panitumumab has antitumor ac tiv ity when ad min is tered as 

a sin gle-agent treat ment to pa tients with met a static colorectal can cer (mCRC) who have failed stan dard 

che mo ther apy. An in de pend ent cen tral ra di ol ogy re view de ter mined that treat ment with panitumumab 

re sulted in a 9% over all re sponse rate and me dian time to pro gres sion of 11.4 weeks. In ves ti ga tors re - 

ported that pa tients with mCRC tu mors ex press ing the EGFr pro tein who re ceived panitumumab 

monotherapy dem on strated a me dian sur vival time of 37.6 weeks and a me dian du ra tion of tu mor re - 



sponse of 18.1 weeks. Sta bi li za tion of dis ease was ob served in 29% of pa tients (n=43). Median 

progression-free survival time was 13.6 weeks. 

Lifecycle Man age ment: In June 2007 Amgen ini ti ated a phase III trial to as sess panitumumab in com - 

bi na tion with che mo ther apy ver sus che mo ther apy alone as first-line ther apy for met a static and/or re cur - 

rent squamous cell car ci noma of the head and neck (SCCHN). The pri mary out come mea sure of the trial, 

which is be ing con ducted in the USA, Aus tra lia, Can ada and Eu rope and in volves 650 pa tients, is over all 

sur vival. Panitumumab is also be ing eval u ated as a monotherapy in the sec ond-line treat ment of SCCHN. 

Phase III tri als are also on go ing as a first- and sec ond-line treatment for colorectal cancer. 

In 2005, Amgen and Abgenix ini ti ated a phase III trial of panitumumab in com bi na tion with Avastin 

(bevacizumab) in the first-line treat ment of met a static colorectal can cer. The clin i cal trial called the 

PACCE (Panitumumab Ad vanced Colorectal Can cer Eval u a tion) study has as end points pro gres sion-free 

sur vival, over all sur vival and re sponse rate. In March 2007, Amgen dis con tin ued the trial due to a sta tis ti - 

cally sig nif i cant ben e fit on sur vival fa vor ing the con trol arm. Amgen hoped PACCE would “leap frog” 

Vectibix into the front-line set ting, de spite not being designed as a registration trial. 

Com pe ti tion: In the 12-month pe riod to the end of Sep tem ber 2008, Vectibix was the num ber 14 lead - 

ing prod uct in the ‘to tal other neoplastics’ ther a peu tic class, with a 0.6% mar ket share, down 21% in 

fixed rate dol lar terms. Roche and its ma jor ity-owned sub sid iary Genentech dom i nate this class with its 

MabThera (rituximab) in first place with 17.8% share (up 14%) fol lowed by Avastin (bevacizumab) 

with 15.6%, up 38% and Herceptin (trastuzumab) in third place with 15.4% share, up 12% over the 

pre vi ous 12-month pe riod. Erbitux took sixth place in the same pe riod with 5.5% share with 15% growth 

over the previous year. 

ImClone Sys tems (USA) and BM-S (USA) have a com pet i tor prod uct Erbitux (cetuximab) on the mar - 

ket, launched in the USA in 2004 and now launched in sev eral Eu ro pean and other mar kets. Other com - 

pet i tors are Genentech’s (USA)/Roche’s (Swit zer land) Avastin and Tarceva (erlotinib). Avastin has been 

on the Jap a nese mar ket for ad vanced/re cur rent colorectal can cer, in com bi na tion with 5-FU che mo ther - 

apy since June 2007. Avastin has also been filed in Ja pan for use in com bi na tion with Roche/Chugai’s 

Xeloda (capecitabine) and Yakult Honsha’s chemotherapeutic Elplat (oxaliplatin), li censed from 

Debiopharm) while Xeloda was filed the same month for colorectal can cer; Elplat is al ready in di cated for 

colorectal can cer in com bi na tion with 5-FU and levofolinate. 

Re sults of a 755-pa tient study (CAIRO II) pre sented in 2008 showed that the ad di tion of Erbitux to a 

treat ment reg i men of FOLFOX and Avastin was as so ci ated with a lower pro gres sion free sur vival of 9.8 

months com pared with 10.7 months in the con trol arm al though over all sur vival was sim i lar at 20.4 

months ver sus 20.3 months with Erbitux. These re sults mir ror those that led to the dis con tinu a tion of the 

Vectibix trial in early 2007 and ac cord ing to an a lysts the gap is clos ing be tween Erbitux and Vectibix with 

the emer gence of the K-RAS as pect which could cre ate a sig nif i cant win dow of op por tu nity for Amgen. 

Amgen is run ning the first phase III clin i cal tri als in colorectal can cer that pro spec tively de fines pa tient 

KRAS status, gaining a potential edge over Erbitux. 

The an a lyst said how ever that al though Amgen has at tempted to limit the la bel in the USA to the KRAS 

wild type only, the FDA has show re sis tance at the ret ro spec tive anal y sis and may re quire an other trial 

(which could take sev eral years). In De cem ber 2008, the FDA on col ogy ad vi sory com mit tee (ODAC) met 

to dis cuss the use of KRAS mu ta tion sta tus as pre dic tive/prog nos tic biomarker to eval u ate pa tients more 

likely to re spond to Vectibix and Erbitux. Eu ro pean la bel ing for the EGFR in hib i tors al ready lim its use to 

pa tients with the KRAS wild-type gene. In No vem ber 2008, the US Na tional Com pre hen sive Can cer Net - 

work (NCCN) rec om mended use of the EGFR in hib i tors (Vectibix and Erbitux) only for pa tients with wild 

KRAS tumors in metastatic colorectal cancer. 



There were an es ti mated 115,000 new cases of colorectal can cer in Ja pan in 2005, the coun try’s sec ond 

most com mon can cer (af ter stom ach) with around one-quar ter of pa tients pre sent ing with dis ease that 

has al ready metastasized; the in ci dence is said to be ris ing with around 38,000 deaths annually. 

Sales/An a lyst Com ment: Sales of Vectibix for Amgen were $153 mil lion in 2008, down 10% over 

2007, its first full-year on the mar ket, sales of $170 mil lion. An a lysts at Mor gan Stan ley, writ ing on 

Amgen in Jan u ary 2009, es ti mate peak global sales of $400 mil lion for Vectibix. They com mented that al - 

though Amgen has a win dow of op por tu nity with the KRAS data in first and sec ond line colorectal can cer, 

and can po ten tially beat Erbitux to this more lu cra tive front-line pa tient pool, Amgen will still need to 

over come Erbitux’ ‘first mover’ ad van tage. The an a lysts view it highly un likely that data could be strong 

enough for Vectibix to be come com pe ti tion for Avastin but more on a par with Erbitux, al low ing it to take 

share in the $1.5 bil lion EGFR an ti body mar ket. The an a lysts fore cast sales of $195 mil lion in 2009, rising 

to $276 million by 2013 for Amgen. 

MOTESANIB, an antiangiogenic small mol e cule that in hib its mul ti ple kin ases in volved in ep i the lial ma - 

lig nan cies and angiogenesis, in clud ing VEGFR, PDGFR and c-kit was in phase III tri als with Takeda, Mil - 

len nium and Amgen (the Takeda On col ogy Com pany) in the USA, Eu rope and Japan in 2009. 

In No vem ber 2008, the tem po rary sus pen sion of pa tient en roll ment in the MONET1 trial of motesanib 

(AMG 706) in the treat ment of nonsmall cell lung can cer (NSCLC) was an nounced. This fol lows a rec om - 

men da tion by the trial’s in de pend ent Data Mon i tor ing Com mit tee (DMC) af ter a planned re view of safety 

data from 600 pa tients. The DMC’s de ci sion is based on the ob ser va tion of a higher early mor tal ity rate in 

the motesanib group com pared with the pla cebo group. Ad di tion ally, the DMC rec om mended im me di ate 


pected hemoptysis rate in these pa tients. The DMC did not rec om mend dis con tinu a tion of motesanib 

ther apy in pa tients with non-squamous NSCLC. In Feb ru ary 2009, an in de pend ent data mon i tor ing com - 

mit tee (DMC) has rec om mended the re sump tion of en roll ment of pa tients with non-squamous nonsmall 

cell lung cancer (NCSLC) into the phase III MONET1 trial of motesanib. 

Li cens ing: In Feb ru ary 2008, as part of a col lab o ra tion with Amgen in Ja pan, Takeda con cluded a li cense 

agree ment for 13 com pounds in clud ing motesanib that Takeda has ob tained rights to ex clu sively de velop 

and mar ket in Ja pan and co-de velop and co-mar ket with Amgen Inc out side of Ja pan. Takeda will pay 

$100 mil lion upfront and pay 100% of de vel op ment in Ja pan and 60% over seas, in ad di tion to mile stone 

pay ments of up to Yen175 million as well as royalties. 

Clin i cal Data: The pla cebo-con trolled, dou ble-blind in ter na tional MONET1 (MOtesanib NSCLC Ef fi cacy 

and Tolerability study) phase III trial has en rolled 1100 of 1240 planned pa tients with ad vanced 

squamous or non-squamous NSCLC. Pa tients were ran dom ized 1:1 to re ceive carboplatin and paclitaxel 

given ev ery three weeks with or with out once-daily 125 mg motesanib. The pri mary end point is over all 

sur vival; sec ond ary end points in clude pro gres sion-free sur vival, ob jec tive re sponse rate in pa tients with 

mea sur able dis ease and duration of response and safety. 

At the ASCO Meet ing 2007, Amgen pre sented data from a multicenter, open-la bel phase II trial of 

motesanib in the treat ment of pa tients with I-131-re sis tant dif fer en ti ated thy roid can cer. The pri mary 

end point was ob jec tive re sponse rate per mod i fied RECIST cri te ria; sec ond ary end points were du ra tion of 

re sponse, pro gres sion-free sur vival and safety. The agent was given orally at 125mg once-daily for up to 

48 weeks or un til ev i dence of dis ease pro gres sion, death or un ac cept able tox ic ity. Tu mor re sponse was 

eval u ated ev ery eight weeks and blood thy ro glob u lin lev els were an a lyzed at study day one and ev ery 

four weeks there af ter. Four teen per cent, 35% and 49% of pa tients achieved a con firmed par tial re - 

sponse, du ra ble sta ble dis ease for 24 weeks or lon ger and clin i cal ben e fit, re spec tively. Eighty-two per - 

cent of pa tients with post-base line thy ro glob u lin as sess ment achieved a de crease in thy ro glob u lin 

con cen tra tion af ter motesanib ther apy. Me dian trough plasma con cen tra tions af ter daily ad min is tra tion 

of 125mg motesanib were be tween IC50 and IC90 val ues (as cer tained by in vi tro HUVEC method). 



Motesanib was tol er a ble with the most frequent adverse events being diarrhea, hypertension and fatigue 

(generally manageable). 

Amgen re ported in No vem ber 2006 re sults from a sin gle-arm, multicenter phase II trial of AMG 706 in 

pa tients with ad vanced high-dose imatinib-re sis tant GISTs. 120 evaluable pa tients re ceived AMG 706 

125mg po un til pro gres sive dis ease or tox ic ity (for at least eight weeks). A clin i cal ben e fit rate of 27%, in - 

clud ing 3% of par tial re sponses and 24% of du ra ble sta ble dis ease greater than or equal to 22 weeks, 

was de ter mined by the RECIST as sess ment. At week eight, 23% of pa tients showed an ob jec tive re - 

sponse as de ter mined by fluorodeoxyglucose-pos i tron emis sion to mog ra phy (FDG-PET) and 33% of pa - 

tients dem on strated an ob jec tive re sponse when eval u ated by Choi cri te ria. The me dian pro gres sion-free 

sur vival was 16 weeks, with 26 week pro gres sion-free sur vival of 27%. Me dian sur vival was 59 weeks. 

Treat ment-re lated ad verse events, which oc curred in 15% or more of all treated pa tients, in cluded di ar - 

rhea (55%), hypertension (48%), fatigue (45%), headache (47%) and nausea (35%). 

TAK 242 (resatorvid), which in hib its pro duc tion of in flam ma tory me di a tors such as cytokines by block - 

ing Toll-like re cep tor 4 (TLR4) sig nal ing, is be ing de vel oped by Takeda for the novel treat ment of se vere 

sep sis. It was in phase III tri als in Eu rope, the USA and Ja pan in 2009. The prod uct ob tained Fast Track 

sta tus in the US in July 2005. Se vere sep sis of ten re sults in or gan dys func tion and has a high mor tal ity 

rate. Lilly’s (USA) Xigris (drotrecogin al pha) is cur rently the only ther apy avail able for the con di tion with 

sev eral ther a peu tic can di dates fail ing over the past few years in clud ing Chiron’s (now Novartis, Swit zer - 

land) tifacogin (still in de vel op ment for other uses) and Shionogi’s (Ja pan) varespladip. 

CBP 501, a G2 check point abrogater (in jec tion) be gan phase II eval u a tion in the US in De cem ber 2008 

with CanBas and Mil len nium (Takeda’s wholly-owned sub sid iary) for ma lig nant pleu ral me so the li oma. 

The trial is ex pected to com plete in De cem ber 2010. The drug in duces can cer cell death by block ing the 

tran si tion of can cer cells through the cell cy cle. Data from a phase I study in di cated that when com bined 

with se lected chemotherapeutic drugs, CBP 501 en hances the anticancer cytotoxic ac tiv ity of these es - 

tab lished treat ments. a phase I trial in lung can cer was also re ported to be underway with CanBas in 

2009. 

Li cens ing: Takeda gained ex clu sive rights to de velop, man u fac ture and mar ket this and backup can cer 

com pounds world wide, ex cept in the US where ac tiv ity will be jointly con ducted from CanBas (USA) in 

March 2007. Takeda will pay CanBas an upfront sum upon the ini ti a tion of the col lab o ra tion and will make 

an eq uity in vest ment in CanBas. Takeda will also make mile stone pay ments to CanBas re lated to clin i cal 

and reg u la tory prog ress, and roy alty payments on sales of the agent. 

GNRH AN A LOGUE: TAP (now Takeda) and Norwood Im mu nol ogy funded a pre clin i cal study at Mas sa - 

chu setts Gen eral Hos pi tal on the po ten tial use of GnRH an a logues in the trans plant set ting, pre vent ing 

or gan re jec tion with out need for long-term immunosuppresssants. Phase II tri als were on go ing in the US 

in 2008. The TAP jv was concluded in May 2008. 

LESTAURTINIB (CEP 701), an orally-avail able ty ro sine kinase in hib i tor, was li censed to TAP (the 

Takeda/Abbott joint ven ture) in 1999 for the US by Cephalon (USA). This po ten tial treat ment for pros tate 

and pan cre atic can cers be gan phase II tri als in pros tate can cer in 2000 with TAP. Cephalon planned clin i - 

cal stud ies for the treat ment of pan cre atic can cer, and in 2002 an ad di tional phase II study was un der 

way for acute myelogenous leukemia. 

The TAP jv was con cluded in May 2008. 

Li cens ing: Cephalon gained rights to this prod uct and a se ries of re lated mol e cules from Kyowa Hakko 

(Ja pan). 

MLN 1202, a hu man ized monoclonal an ti body that tar gets the CCR2 chemokine re cep tor has po ten tial 

util ity for the treat ment of mul ti ple scle ro sis, as well as other in flam ma tory con di tions, in clud ing ath ero - 



scle ro sis, scleroderma, restenosis and fi bro sis. It is un der go ing eval u a tion in a Eu ro pean/Ca na dian phase 

II trial in pa tients with re laps ing-re mit ting mul ti ple scle ro sis and a US phase II trial in pa tients at risk for 

atherosclerotic car dio vas cu lar dis ease as well as pre clin i cal stud ies in the USA for the treatment of 

scleroderma with Millennium (now Takeda). 

MLN 518 (tandutnib), an in hib i tor of the FLT3 re cep tor ty ro sine kinase (RTK), as an orally de liv ered ther - 

apy with po ten tial in the treat ment of acute myelogenous leu ke mia (AML) and glioblastoma was in phase 

II tri als in the US in 2009 with Mil len nium (now Takeda). 

MLN 4924 is a small mol e cule in hib i tor of the Nedd 8 ac ti vat ing en zyme (NAE) which con trols a sub set of 

pro teins in the ubiquitin proteaseome path way that reg u late can cer cell sur vival. It was un der go ing two 

phase I dose es ca la tion tri als with Mil len nium (now Takeda) in the US in 2009. 

MLN 8054, an orally act ing, small mol e cule au rora A kinase in hib i tor for the po ten tial treat ment of ad - 

vanced ma lig nan cies is un der go ing US phase I eval u a tion in pa tients with a range of solid and he ma to - 

log i cal tu mors with Mil len nium (now Takeda) in 2009. 

MLN 8054, an orally act ing, small mol e cule au rora A kinase in hib i tor for the po ten tial treat ment of ad - 

vanced ma lig nan cies is un der go ing US phase I eval u a tion in pa tients with a range of solid and he ma to - 

log i cal tu mors with Mil len nium (now Takeda) in 2009. 

MLN 2238, a sec ond-gen er a tion proteasome in hib i tor, for the po ten tial treat ment of can cer was un der - 

go ing pre clin i cal eval u a tion in 2008 with Mil len nium (now Takeda). 

AMG 655, a fully hu man monoclonal agonistic an ti body tar get ing the extracellular do main of the hu man 

TNF-re lated apoptosis-in duc ing ligand (TRAIL) re cep tor 2 (TR-2), for the po ten tial treat ment of can cer 

was in phase 1 de vel op ment with Takeda in Ja pan in 2009. In Feb ru ary 2008 Amgen and Takeda signed 

an agree ment un der which Takeda will de velop and com mer cial ize in Ja pan up to 13 of Amgen’s early- to 

mid clin i cal-stage can di dates, in clud ing AMG 655. It is un der go ing phase II tri als in the US in the treat - 

ment of solid tumors and lymphomas with Amgen. 

TAK 285, an oral HER2 in hib i tor was in a phase I trial for solid tu mors with Takeda in 2009; pre clin i cal re - 

sults have been re ported. 

TAK 700, an oral sex hor mone syn the sis in hib i tor was re ported to be in phase I tri als for pros tate can cer 

with Takeda in 2009. 

TAK 448, a go nad o tro pin-re leas ing hor mone (GnRH) mod u la tor for the po ten tial treat ment of pros tate 

can cer, that re duces tes tos ter one lev els rap idly and strongly is un der go ing phase I eval u a tion in Japan in 

2009. 

TAK 593, an oral in hib i tor of the ty ro sine kin ases for the VEGFR and PDGFR fam i lies, was un der go ing 

phase I eval u a tion in Ja pan for the po ten tial treat ment of solid tumors in 2009. 

AMG 386, an angiopoietin (ANG) re cep tor an tag o nist, is in phase II stud ies with Amgen for the po ten tial 

treat ment of solid tu mors. In Feb ru ary 2008 Amgen and Takeda signed an agree ment un der which 

Takeda will de velop and com mer cial ize in Ja pan up to 13 of Amgen’s early- to mid clin i cal-stage can di - 

dates, including AMG 386. 

HUL 2G7, a monoclonal an ti body with po ten tial in the treat ment of brain tu mors in clud ing gliomas. HuL 

2G7 is de signed to in hibit hepatocyte growth fac tor (HGF), which is in volved in tu mor cell di vi sion, tu mor 

angiogenesis and tu mor cell re sis tance to che mo ther apy and ra di a tion. The monoclonal is un der go ing 

pre clin i cal eval u a tion in the USA. Gal axy (USA) an tic i pates com menc ing clin i cal tri als in 2007 and in 2008 

Takeda con firmed that prep a ra tion for clinical trials is ongoing. 



Li cens ing: In July 2006, Gal axy signed a li cens ing agree ment with Takeda, grant ing the lat ter ex clu sive, 

world wide rights to de velop, man u fac ture and mar ket HuL 2G7. Gal axy will re ceive an upfront $2 mil lion 

li cens ing fee from Takeda, as well as mile stone pay ments de pend ent on the achieve ment of cer tain de - 

vel op ment and reg u la tory mile stones. Gal axy will also be en ti tled to roy al ties on prod uct sales. Takeda 

will fund fur ther re search ac tiv i ties at Gal axy on HuL 2G7 and suc ces sor agents, for a period of four years. 

AMG 479, a fully hu man monoclonal an ti body tar geted to in su lin-like growth fac tor 1 (IGF-1), with po - 

ten tial in the treat ment of can cer was in phase II tri als in the USA with Amgen in 2009. In Feb ru ary 2008 

Amgen and Takeda signed an agree ment un der which Takeda will de velop and com mer cial ize in Ja pan up 

to 13 of Amgen’s early- to mid clin i cal-stage can di dates, including AMG 479. 

Blood and Blood-Forming Organ Agents 

pegylated erythropoietin receptor agonist AF 37702 B3X III 

factor xa inhibitor TAK 442 B2C1 II 

HEMATIDE (pegylated eryth ro poi e tin re cep tor ag o nist) was in phase III tri als in the US and Eu rope, and 

phase II in Ja pan in 2009, for the treat ment of ane mia in di al y sis and predialysis chronic kid ney dis ease 

pa tients with pure red cell aplasia (PCRA, an au to im mune re ac tion to re com bi nant eryth ro poi e tin). In - 

terim re sults re leased in April 2008 sug gested that it is safe and ef fec tive in kid ney di al y sis pa tients and 

suc cess fully main tained he mo glo bin lev els in the target range over 18 months of treatment. 

A phase I trial (to en rol 100 pa tients with non small cell lung, breast or pros tate can cer) com menced in 

the US in Jan u ary 2008 for ane mia in can cer pa tients un der go ing che mo ther apy and sim i lar phase I tri als 

have al ready been ini ti ated in the EU and Ja pan. In Au gust 2008 how ever, Takeda and Affymax sus - 

pended de vel op ment of Hematide as a treat ment for che mo ther apy-in duced ane mia, and will fo cus on 

de vel op ing the agent as a treat ment for ane mia re lated to chronic kid ney dis ease be cause of un cer tain 

reg u la tory pros pects for such agents in on col ogy in di ca tions; the FDA added ‘black box’ warn ings to 

eryth ro poi e tin prod ucts in 2008. No fur ther en roll ment will take place in the ongoing phase I trial of 

Hematide in cancer patients. 

Li cens ing: In Feb ru ary 2006, Affymax granted Takeda an ex clu sive li cense to de velop and com mer cial - 

ize Hematide in Ja pan. Takeda will pay $17 mil lion upfront and pur chase $10 mil lion of Affymax’s stock. 

In ad di tion, Affymax is en ti tled to re ceive clin i cal and reg u la tory based mile stone pay ments to tal ing $75 

mil lion as well as a dou ble-digit roy alty on sales upon Jap a nese launch; al to gether the deal was val ued at 

$100m to Affymax. Takeda is re spon si ble for all de vel op ment and com mer cial iza tion costs in Ja pan. 

Affymax will man u fac ture and sup ply the drug sub stance for Takeda to man u fac ture the fi nal com mer cial 

prod uct for use in Ja pan. This agree ment was mod i fied in June 2006 to grant Takeda rights to de velop 

and com mer cial ize Hematide out side the USA, and to col lab o rate with Affymax on the de vel op ment of the 

prod uct in the USA. A $10 mil lion pay ment was made by Takeda in Feb ru ary 2007 fol low ing the com ple - 

tion of phase I test ing in nor mal healthy volunteers. Takeda is to commercialize Hematide in Europe also 

upon approval. 

Clin i cal Data: In 2008, Affymax com pleted en roll ment in the phase III pro gram of Hematide in chronic 

re nal fail ure (PEARL 1, PEARL2, EM ER ALD 1, and EM ER ALD 2) in volv ing a to tal of 2,600 chronic re nal fail - 

ure pa tients with the aim of com ple tion, data col lec tion and NDA fil ing in 2010. Takeda an nounced re sults 

of a phase II clin i cal trial of Hematide in No vem ber 2007 in dem on strat ing that six months of in jec tion 

with the prod uct re stored he mo glo bin to the tar get range and elim i nated the need for red blood cell 

transfusion in the patients studied. 

Com pe ti tion: This syn thetic drug will com pete with bi o logic ane mia prod ucts that have faced re stric - 

tions over safety and po ten tial over use con cerns. The Jap a nese mar ket for erythropoiesis agents is worth 

around $1 bil lion an nu ally, cur rently dom i nated by re com bi nant erythropoietins such as Roche’s (Swit - 



zer land) Epogin (epoetin beta) which has been filed for ad di tional do mes tic ap proval in chemotherapy 

induced anemia. 

TAK 442, an orally ac tive, se lec tive and com pet i tive in hib i tor of ac ti vated fac tor Xa, as a po ten tial ther - 

apy for ve nous or ar te rial thromboembolism, such as pul mo nary em bo lism and ce re bral in farc tion. 

Takeda ini ti ated a US/Eu ro pean phase II trial of TAK 442 in 2008 and phase I eval u a tion was also re - 

ported to be underway in Japan in 2009. 

Cardiovascular System Agents 

azilsartan + pioglitazone — C9C III 

azilsartan medoxomil TAK 491 C9C III 

azilsartan TAK 536 C9C II 

epa/dha agent TAK 085 C10A9 II 

ARB for hypertension TAK 591 C9C I 

AZILSARTAN + PIOGLITAZONE, a fixed com bi na tion of pioglitazone, a thiazolidinedione, plus 

azilsartan, an an gio ten sin II re cep tor an tag o nist, for the po ten tial treat ment of Type 2 di a be tes as so ci - 

ated with hy per ten sion. A US phase III trial pro gram of the prod uct in pa tients with Type 2 di a be tes as so - 

ci ated with hy per ten sion began in the USA in 2006. 

TAK 491, an an gio ten sin II re cep tor an tag o nist with po ten tial in the treat ment of hy per ten sion was un - 

der go ing phase III eval u a tion in Eu rope and the USA in 2009. A ran dom ized, dou ble-blind, pla cebo-con - 

trolled phase II trial, be ing con ducted in the USA, Mex ico and Peru, eval u ated the safety, ef fi cacy and 

tolerability of treat ment with TAK 491 for eight weeks in ap prox i mately 420 pa tients with hy per ten sion. 

The pri mary endpoint was diastolic blood pressure. 

TAK 491 is ex pected to have a stron ger antihypertensive ac tion and to dis play a su pe rior pro file in im - 

prov ing in su lin re sis tance and de creas ing proteinuria com pared with mar keted an gio ten sin receptor 

blockers. 

TAK 536 (azilisartan) is an an gio ten sin II re cep tor an tag o nist, in phase II de vel op ment for the treat ment 

of hy per ten sion in the USA and Eu rope and also en tered phase II tri als in Ja pan in 2007, all re ported to be 

ongoing in 2009. 

In July 2006, Takeda be gan a phase III trial pro gram of a fixed com bi na tion of pioglitazone plus TAK 536 

for the treat ment of Type 2 di a be tes as so ci ated with hy per ten sion (see sep a rate drug record). 

OMACOR (TAK 085), omega-3-acid ethyl es ters, en tered phase II tri als for the treat ment of 

hyperlipidemia in Ja pan with Takeda in 2007, on go ing in 2009. In 2005, Takeda li censed the Jap a nese 

rights to Omacor (TAK 085) from Pronova. 

TAK 591, an an gio ten sin II re cep tor blocker was in phase I tri als for the treat ment of hy per ten sion in 

2009. 



Central Nervous System Agents 

idebenone SNT MC17 N6D, N7X, M5X Filed 

bis-aryl-sulphanyl amine LU AA21004 N6A9 III 

venlafaxine WY 45030 N6A5, N5C, N7X III 

bis-aryl-sulphanyl amine LU AA24530 N6A9 II 

diabetic neuropathy therapy TAK 428 N7X II 

PHN therapy TAK 583 N7X II 

neuroregeneration enhancer TAK 065 N4A, N7D9 I 

IDEBENONE is a com pound orig i nally de vel oped by Santhera (Swit zer land). It was orig i nally de vel oped 

as a brain me tab o lism-im prov ing drug and was launched in a num ber of coun tries by var i ous li cens ees, 

no ta bly Abbott (USA) and Takeda. It was launched as Avan in Ja pan in 1987 by Takeda, but was delisted 

from re im burse ment in Ja pan in 1998, to gether with a num ber of sim i lar prod ucts, due to efficacy 

concerns. 

Santhera has now be gun tri als in new in di ca tions. In 2005, Santhera com menced a Eu ro pean phase III 

trial of idebenone in Friedreich’s Ataxia (FRDA) pa tients. In Au gust 2007, the EMEA ac cepted the fil ing of 

an MAA for idebenone for the treat ment of Friedreich’s Ataxia; a reg u la tory fil ing in this in di ca tion was ac - 

cepted by Swissmedic in Oc to ber 2007 and Health Can ada in No vem ber 2007. Idebenone has been 

granted or phan drug des ig na tion in the EU and could be come the first ap proved prod uct for the treat - 

ment of FRDA. A US phase III trial in pa tients with Friedreich’s Ataxia was ini ti ated in the USA in Sep tem - 

ber 2007. In No vem ber 2008 Santhera re ported that the EMEA has con firmed its orig i nal neg a tive 

opin ion (is sued in July 2008) on the EU MAA for idebenone (SOVRIMA;SNT MC17) in Friedreich’s ataxia. 

The CHMP of the EMEA an nounced that it pre ferred to wait for ad di tional re sults from at least one of two 

piv otal tri als. Santhera in tends to file for marketing authorization in the USA and the EU in 2009. 

Santhera is also con duct ing a phase II trial to eval u ate the agent as a ther apy for Du chenne Mus cu lar 

Dystropy. Santhera is de vel op ing idebenone as a po ten tial treat ment for Leber’s he red i tary op tic neu rop - 

a thy; reg u la tory ap prov als for phase IIa tri als in the UK and Ger many have been granted. 

Li cens ing: In 2005, Takeda ob tained mar ket ing rights in the EU and Swit zer land to idebenone for the 

treat ment of Friedreich’s ataxia; Santhera will con duct all clin i cal tri als of idebenone. In Au gust 2007 

Santhera granted Takeda mar ket ing rights in the EU and Swit zer land to idebenone for the treat ment of 

DMD. 

Pat ents: Takeda filed a pri or ity pat ent ap pli ca tion in Ja pan in 1974. All com po si tion of mat ter pat ents for 

idebenone have ex pired and Santhera holds a method of use pat ent for idebenone for the treat ment of 

Friedreich’s ataxia, in the USA and Canada. 

LU AA21004, a bis-aryl-sulphanyl amine SRI an ti de pres sant com pound en tered phase III de vel op ment 

for the treat ment of ma jor de pres sive dis or der (MDD) in De cem ber 2007. A phase I trial of Lu AA21004 

was re ported to be un der way in Ja pan in 2009. Bis-aryl-sulphanyl amines is a new chem i cal class of novel 

psychotropics, and ac cord ing to Lundbeck, the in vi tro phar ma co log i cal pro file LU AA21004 shows that it 

com bines po tent ef fect on sev eral se ro to nin re cep tors and se ro to nin trans porter pro teins. The com pound 

acts as a se ro to nin mod u la tor and stimulator and mod u lates rel e vant parts of the neurochemical ar chi - 

tec ture in the brain in a ben e fi cial way. Com pared with cur rently ap proved an ti de pres sants, pre clin i cal 

mod els have dem on strated that the com pounds have the po ten tial to ad dress im por tant un met needs for 

pa tients in terms of both fast on set of ef fect and in creased ef fi cacy. This prod uct is one of Takeda’s pri or - 

ity prod ucts in the CNS field and the advancement to phase III represents a significant achievement for 

Takeda’s CNS pipeline. 

Li cens ing: In Sep tem ber 2007, Takeda an nounced a stra te gic al li ance with Lundbeck (Den mark) for the 

ex clu sive co-de vel op ment and co-com mer cial iza tion in the USA and Ja pan of sev eral com pounds in 



Lundbeck’s pipe line for the treat ment of mood and anx i ety dis or ders. The part ner ship will ini tially fo cus 

on co-de vel op ment and co-com mer cial iza tion of Lu AA21004 and Lu AA24530 for mood and anx i ety dis - 

or ders, but the agree ment in cludes an op tion un der cer tain con di tions to in clude two other com pounds of 

the same class in ear lier stages of de vel op ment. If ap proved, the com pa nies plan to co-pro mote the com - 

pounds in the USA and Ja pan. Un der the terms of the agree ment, Lundbeck will re ceive an ini tial pay ment 

of $40 mil lion and po ten tial max i mum of $345 mil lion in ad di tional de vel op ment mile stone pay ments. 

Takeda and Lundbeck will jointly com plete the de vel op ment programmes, with Takeda book ing the to tal 

sales and fund ing the ma jor ity of the re main ing de vel op ment ac tiv i ties. Lundbeck will re ceive a share of 

the rev e nue gen er ated in the USA and Ja pan as well as roy alty pay ments on Takeda’s share of revenues. 

Takeda considers that this alliance will enhance its core CNS franchise. 

Clin i cal Data: Over 2,000 pa tients are ex pected to en rol in the phase III pro gram glob ally. Phase II tri als 

dem on strated sig nif i cant im prove ments over pla cebo on pri mary end points and a good safety profile. 

EFFEXOR (venlafaxine), a se ro to nin and noradrenaline reuptake in hib i tor, is a struc tur ally novel an ti de - 

pres sant, first launched in the USA in 1994. Orig i na tor Wyeth has since launched it world wide out side Ja - 

pan. Wyeth KK (Ja pan), in which Takeda has a 20% stake, is de vel op ing the drug in Ja pan. Phase III tri als 

com menced in Ja pan to eval u ate venlafaxine for de pres sion and gen er al ized anx i ety dis or der (GAD) and 

were reported to be ongoing in 2006. 

Clin i cal Data: Re sults have been re leased from over 30 mul ti na tional, dou ble-blind, phase IV post-mar - 

ket ing sur veil lance tri als in more than 7000 pa tients with ma jor de pres sive dis or der ran dom ized to re - 

ceive ei ther Effexor, Effexor XR (venlafaxine ex tended-re lease for mu la tion), fluoxetine, paroxetine, 

citalopram, fluvoxamine, or sertraline. Data showed that pa tients treated with Effexor and Effexor XR had 

sig nif i cantly higher re mis sion rates than those treated with other SSRIs in the trial. Effexor and Effexor 

XR were both more ef fec tive than the other SSRIs in the treat ment of the phys i cal anx i ety/somatization 

symp toms of de pres sion. In the Effexor/Effexor XR group, 38% pa tients achieved res o lu tion of the gen - 

eral so matic symp toms, com pared with 32% of pa tients re ceiv ing SSRIs and 25% of patients 

administered placebo. 

In Jan u ary 2004, phase III tri als com menced in Ja pan to eval u ate venlafaxine. Re sults were re leased 

from over 30 mul ti na tional, dou ble-blind, phase IV post-mar ket ing sur veil lance tri als in more than 7000 

pa tients with ma jor de pres sive dis or der ran dom ized to re ceive ei ther Effexor, Effexor XR (venlafaxine ex - 

tended-re lease for mu la tion), fluoxetine, paroxetine, citalopram, fluvoxamine, or sertraline. Data showed 

that pa tients treated with Effexor and Effexor XR had sig nif i cantly higher re mis sion rates than those 

treated with other SSRIs in the trial. Effexor and Effexor XR were both more ef fec tive than the other 

SSRIs in the treat ment of the phys i cal anx i ety/somatization symp toms of de pres sion. In the 

Effexor/Effexor XR group, 38% pa tients achieved res o lu tion of the gen eral so matic symp toms, com pared 

with 32% of pa tients re ceiv ing SSRIs and 25% of patients administered placebo. 

LU AA24530 was re ported to have en tered phase I de vel op ment with Takeda in Ja pan in 2009 for mood 

and anx i ety dis or ders/de pres sion while phase II de vel op ment was on go ing in Eu rope. The Eu ro pean trial 

is ex pected to en rol 600 pa tients with a fil ing is anticipated from 2009. 

Li cens ing: In Sep tem ber 2007, Takeda an nounced a stra te gic al li ance with Lundbeck (Den mark) for the 

ex clu sive co-de vel op ment and co-com mer cial iza tion in the USA and Ja pan of sev eral com pounds in 

Lundbeck’s pipe line for the treat ment of mood and anx i ety dis or ders. The part ner ship will ini tially fo cus 

on co-de vel op ment and co-com mer cial iza tion of Lu AA21004 and Lu AA24530 for mood and anx i ety dis - 

or ders, but the agree ment in cludes an op tion un der cer tain con di tions to in clude two other com pounds of 

the same class in ear lier stages of de vel op ment. If ap proved, the com pa nies plan to co-pro mote the com - 

pounds in the USA and Ja pan. Un der the terms of the agree ment, Lundbeck will re ceive an ini tial pay ment 

of $40 mil lion and po ten tial max i mum of $345 mil lion in ad di tional de vel op ment mile stone pay ments. 

Takeda and Lundbeck will jointly com plete the de vel op ment programmes, with Takeda book ing the to tal 



sales and fund ing the ma jor ity of the re main ing de vel op ment ac tiv i ties. Lundbeck will re ceive a share of 

the rev e nue gen er ated in the USA and Ja pan as well as roy alty pay ments on Takeda’s share of revenues. 

Takeda considers that this alliance will enhance its core CNS franchise. 

TAK 428 is a treat ment for di a betic neu rop a thy, in phase II tri als in Eu rope and the USA in 2009. De vel - 

oped in-house, it is an enhancer of neu ral growth. 

TAK 583, for the po ten tial treat ment of postherpetic neu ral gia (PHN). In 2008 it was re ported to be in 

phase II stud ies in the US, Ja pan and Eu rope for pain ful di a betic neu rop a thy (PDN) and di a betic pe riph - 

eral neu rop a thy (DPN) and in the US and Eu rope for postherpatic neuralgia (PHN). 

TAK 065, a neuroregeneration enhancer, was in phase I tri als with Takeda in 2009 for the treat ment of 

Alz hei mer’s and Par kin son’s dis ease. 

Genitourinary System/Sex Hormones 

asoprisnil J 867 G2X9 III 

urinary incontinence therapy TAK 363, TRK 130 G4D I 

SARM LGD 2226 G3B, M5B Preclinical 

ASOPRISNIL (J 867), a pro ges ter one re cep tor mod u la tor is be ing de vel oped by TAP for the treat ment of 

endometriosis, fib roids and hor mone de fi ciency. It is an orally ac tive SPRM (se lec tive pro ges ter one re - 

cep tor mod u la tor). It could be the first SPRM to be in tro duced for core gynecological applications. 

In 2003, TAP be gan phase III tri als of asoprisnil in the USA for the treat ment of fib roids and these had 

com pleted and were be ing eval u ated in June 2005. In 2004, Schering AG (Ger many) was con duct ing 

phase III tri als with asoprisnil, a treat ment of myomas, which are be nign tu mors of the uter ine mus cle. 

Schering AG an nounced in Feb ru ary 2005 that pre lim i nary re sults from a phase III trial in pa tients with 

dys func tional bleed ing as so ci ated with fib roids and myomas, showed that the agent re duced tu mor size. 

Schering AG an tic i pates reg u la tory fil ings for the pro ges ter one re cep tor mod u la tor dur ing 2006. Phase II 

tri als are on go ing in the USA for the treatment of endometriosis. 

The TAP jv con cluded in May 2008. 

Li cens ing: Asoprisnil was orig i nally de vel oped by Schering AG’s Jenapharm sub sid iary. Jenapharm li - 

censed the US rights to TAP prior to 1996, when it was ac quired by Schering AG, which re ceives roy al ties 

on fu ture sales of the agent. 

TAK 363/TRK 130, a com pound for the po ten tial treat ment of uri nary in con ti nence/over ac tive blad der, 

is in joint de vel op ment with Takeda and Toray (Ja pan). Phase I tri als in the US were ini ti ated in 2007 and 

ongoing in 2009. 

Li cens ing: In April 2005, the com pa nies an nounced that they had signed an agree ment to co-de velop 

the com pound. Toray will mar ket the agent in Ja pan, and Takeda will mar ket the com pound in over seas 

ter ri to ries. The com pound was dis cov ered in Toray’s com pound li brary through joint re search by both 

companies. 

Com pe ti tion: Over ac tive blad der symp toms are now mostly treated with anticholinergics and newer 

agents such as Astellas’ (Ja pan) Vesicare (solfenacin) and Novartis’ (Swit zer land) Enablex 

(darifenacin) which have re cently en tered the mar ket, al though these still have side ef fects of dry mouth 

and con sti pa tion. Takeda and Toray are con fi dent that this new drug will show ef fi cacy and side effect 

advantages. 



LGD 2226 is the lead ing com pound in a se ries of se lec tive an dro gen re cep tor mod u la tors (SARMs), orig i - 

nally de vel oped by Ligand (USA). SARMs con trib ute to the pre ven tion and treat ment of cer tain dis eases, 

in clud ing male and fe male sex ual dys func tion, male and fe male os teo po ro sis, frailty and male 

hypogonadism. Pre clin i cal stud ies have been con ducted in the USA. Ligand and TAP re ported in De cem - 

ber 2003 that the com pa nies had ex tended their agree ment to dis cover and de velop SARMs. The agents 

have po ten tial in the treat ment of male and fe male sex ual dysfunction, osteoporosis and male 

hypogonadism. 

Li cens ing: In 2001, Ligand granted TAP Pharmaceuticals ex clu sive world wide rights to man u fac ture and 

sell se lec tive an dro gen re cep tor mod u la tors (SARMs), in clud ing LGD 2226, which treat an dro gen-re lated 

dis eases. Un der the terms of the deal, TAP has been granted ex clu sive world wide rights to man u fac ture 

and sell any prod ucts re sult ing from the col lab o ra tion in its field, in clud ing treat ment and pre ven tion of 

hypogonadism, male sex ual dys func tion, fe male os teo po ro sis, male HRT and other in di ca tions not re - 

tained by Ligand. Ligand could po ten tially re ceive $44 mil lion in re search fund ing and mile stones if two 

prod ucts are suc cess fully de vel oped dur ing the col lab o ra tion. It may also re ceive roy al ties if com pounds 

are com mer cial ized. Ligand re tains cer tain rights in the an dro gen re cep tor field, in clud ing the prevention 

or treatment of prostate cancer, BPH, acne and hirsutism. 

Hormonal Agents 

injectable gnrh modulator TAK 683 H4X, L1X9 I 

lh-rh receptor antagonist TAK 385 H1C3 I 

TAK 683, an in ject able GnRH mod u la tor was re ported to be in phase I tri als for pros tate can cer with 

Takeda in 2008. 

TAK 385, an oral luteinizing hor mone-re leas ing hor mone (LH-RH) re cep tor an tag o nist for the treat ment 

of endometriosis and uterus myoma was re ported to be in phase I tri als in Ja pan with Takeda in 2009. 

Musculoskeletal System Agents 

febuxostat TMX 67, TEI 6720 M4A Approved 

antirheumatic TAK 783 M1C II 

P38 MAP kinase Inhibitor TAK 715 M1C II 

inflammatory disease therapy MLN 3701 M1C I 

COX inhibitor XEN 401 M1A1 Preclinical 

MAb, interleukin-1, Amgen AMG 108 M1C Preclinical 

FEBUXOSTAT (TMX 67) is an oral xanthine oxidase in hib i tor (XAO) with po ten tial in the treat ment of 

gout. Febuxostat is await ing reg u la tory ap proval in the USA, where an NDA was filed in De cem ber 2004 

by TAP, for the man age ment of hyperuricemia in pa tients with chronic gout, sup ported by data from over 

4,000 pa tients. Takeda re ceived full North Amer i can rights to febuxostat in May 2008 fol low ing the con - 

clu sion of a joint ven ture be tween Abbott and Takeda (TAP). In No vem ber 2008 Takeda an nounced that 

the Ar thri tis Ad vi sory Com mit tee of the FDA has rec om mended ap proval of febuxostat for the treat ment 

of hyperuricemia in pa tients with gout; the panel voted 12 to zero in fa vor of ap proval, with one ab sten - 

tion. The panel did how ever flag a po ten tial car dio vas cu lar con cern which they ad vise the FDA to study 

fur ther through post-ap proval chan nels. The ‘ap prov able’ let ter was a ma jor reg u la tory mile stone in it self 

for febuxostat af ter two pre vi ous ‘ap prov able’ let ters over the safety profile and full FDA approval was 

finally granted in February 2009. 



Orig i na tor Teijin (Ja pan) is con duct ing phase III tri als in Ja pan. In May 2005, Teijin an nounced that the 

Jap a nese reg u la tory au thor i ties would re quire ad di tional clin i cal tri als to be con ducted for the drug, which 

had been sub mit ted for ap proval in Ja pan in April 2004 for the treat ment of gout and hyperuricemia. 

Li cens ing: Febuxostat was li censed to TAP, the jv be tween Abbott and Takeda, in 1999 by orig i na tor 

Teijin. Un der the terms of the deal, TAP will de velop the drug in the USA, and has been granted mar ket ing 

rights in Can ada and the USA. Teijin has also li censed rights to Ipsen in Eu rope, where febuxostat was ap - 

proved in May 2008 and SK Chem i cal in South Ko rea. Takeda re ceived North Amer i can rights to 

febuxostat in May 2008 fol low ing the con clu sion of a joint ven ture be tween Abbott and Takeda (TAP). 

Clin i cal Data: The Third trial, CON FIRMS, was con ducted in 2,269 sub jects in which Takeda eval u ated 

the ef fi cacy and safety of 40mg and 80mg doses of febuxostat com pared with stan dard treat ment 

allopurinol for six months. Re sults showed non in fe ri or ity to allopurinol at the lower dose and sta tis ti cally 

sig nif i cant su pe ri or ity in the higher dose where 67% of pa tients tak ing 80mg dose and 45% in the 40mg 

dose and 42% tak ing allopurinol reached the pri mary end point of se rum uric acid (sUA) lev els be low 

6mg/dl. Fur ther more, both doses were su pe rior to allopurinol in pa tients with mild-to-mod er ate re nal im - 

pair ment. Few car dio vas cu lar events were re ported and these were even be tween the groups febuxostat 

(16) and allopurinol (17) al though the FDA ad vi sory group could not ex clude the pos si bil ity which is ex ac - 

er bated by the in creased car dio vas cu lar risk in this pa tient pop u la tion (1.5 times greater than the gen eral 

pop u la tion). The ad vi sory group has ques tioned the popultation of pa tients which did not in clude el derly 

in di vid u als that would man i fest a truer pic ture of pos si ble car dio vas cu lar mor bid i ties as well as the 

six-month time frame which would be too short to un cover car dio vas cu lar risks in a drug that will be 

taken for life. It was counterargued that the un met med i cal need superceded the po ten tial car dio vas cu lar 

risk. The com mit tee rec om mended that any re main ing ques tions con cern ing car dio vas cu lar safety be 

ad dressed by a ran dom ized clin i cal trial and an ob ser va tional study that would fol low pa tients for car dio - 

vas cu lar events. Takeda has al ready pro posed a phase IV clin i cal out comes study focusing on prevention 

of gout flares and all aspects of safety, the design of which it says is fluid and yet to be discussed with the 

FDA. 

Re sults pre sented at the Amer i can Col lege of Rheumatology meet ing in 2002 sug gested that the drug is 

safe and ef fec tive in the treat ment of hyperuricemia and gout. In a phase II trial in volv ing 145 pa tients, 

febuxostat sig nif i cantly re duced se rum urate lev els at all doses tested (40-80 mg once daily) and was well 

tol er ated for up to four weeks. The only se ri ous ad verse ef fects thought to be pos si bly re lated to 

febuxostat was one case of Guillain-Barre syndrome. 

In Oc to ber 2004, TAP an nounced re sults from its phase I and II clin i cal tri als of febuxostat for gout at the 

68th An nual Sci en tific Meet ing of the Amer i can Col lege of Rheumatology. Study find ings showed that 

treat ment with the novel com pound low ered uric acid lev els. More over, in the ma jor ity of these pa tients, 

long-term treat ment with febuxostat (up to two years) re sulted in sig nif i cant re duc tion and main te nance 

of se rum urate (sUA) lev els be low 6.0mg/dl. Study par tic i pants were ini tially given 80 mg/day of the 

com pound and the dose was then ad justed as nec es sary to ei ther 40 mg/day or 120 mg/day and were to 

achieve a sta ble dose by study week 28 based on sUA lev els. A to tal of 116 pa tients be gan the open-la bel 

study for at least two years. Pa tients ex hib ited rapid re duc tion in sUA lev els and most (74-81%) pa tients 

main tained sUA levels of less than 6.0 mg/dl throughout the study. 

In De cem ber 2004, TAP Phar ma ceu ti cal Prod ucts an nounced that it had sub mit ted an NDA with the FDA 

for 80 and 120 mg febuxostat for the man age ment of hyperuricemia in pa tients with chronic gout. The 

NDA sub mis sion in cludes one of the larg est phase III stud ies of chronic gout pa tients in the United States 

to date. Ex perts rec og nize that the stan dard goal in the treat ment of chronic gout is the re duc tion and 

main te nance of sUA lev els of less than 6 mg/dL. The over all in ci dence of ad verse re ac tions in clin i cal stud - 

ies was sim i lar among treat ment groups. The most com monly re ported ad verse re ac tions were: liver 

func tion test ab nor mal i ties, di ar rhea, head ache and nau sea. Ad verse events among trial par tic i pants 

were generally self-limiting and mild-to-moderate in severity. 



Phase III data pre sented at the Amer i can Col lege of Rheumatology in Texas in Oc to ber 2004 in cluded a 

TAP-spon sored study, which was de tailed in a late-break ing ab stract ses sion, and two Teijin-spon sored 

stud ies con ducted in Ja pan, named FAL CON and FLIGHT. TAP’s head-to-head com par i son of febuxostat 

(80 or 120 mg/day) with allopurinol (300 mg once daily) found in fa vor of febuxostat. IN the 760-pa tient, 

one-year study, more pa tients on the TAP/Teijin com pound met the pri mary end point (UA lev els of less 

than 6.0 mg/dl at each of their last three monthly mea sure ments) than those on allopurinol. All pa tients 

en rolled had gout and lev els of sUA greater than 8.0 mg/dl at the start of the trial. Febuxostat did not sig - 

nif i cantly re duce tophus area (ag gre gates of urate crys tals) at 52 weeks, but the higher dose showed sig - 

nif i cance on this end point at an ear lier time point in the trial. How ever, pa tients who did reach the goal of 

sUA of less than 6 mg/dl in all treat ment groups had fewer gout at tacks and a greater median reduction in 

tophus area. 

The FAL CON study also found a fa vor able com par i son on febuxostat with allopurinol. It used a lower dose 

of both drugs than the TAP study (40 mg af ter an in tro duc tory 12 days at 10 mg and allopurinol at 100 mg 

bid). The pa tients tak ing febuxostat has a 40.5% de crease over base line lev els of sUA at the end of the 

44-day trial, com pared with a 33.9% re duc tion in the allopurinol group. Febuxostat seemed to work just 

as well in pa tients who were un der-excretors of uric acid as in those who has hyperuricemia. The phase 

III trial had a sim i lar safety pro file of the TAP trial. 

The six-week FIGHT trial dem on strated that sig nif i cantly more pa tients on febuxostat (20 or 40 mg) had 

less than 6mg/dl de creases in sUA com pared with pla cebo. At least one ad verse event was seen in 71.0% 

of febuxostat-treated pa tients, com pared with 79.4% of pa tients on pla cebo. Those as so ci ated with 

febuxostat in cluded gout flare, in creases in C-re ac tive pro tein and creatinine phosphokinase, and the 

common cold. 

Com pe ti tion: An es ti mated 5.1 mil lion peo ple suf fer from Gout in the USA. Cur rent first line (gold stan - 

dard) ther apy for gout is the ge neric XAO allopurinol (Zyloric), first ap proved in 1966, but about 2% of 

pa tients are al ler gic to this drug and fewer than half of pa tients achieve tar get se rum uric acid (sUA) lev - 

els of less than 6mg/dl. There is a need for new gout ther a pies and if ap proved, Uloric will be the first new 

oral drug ap proved in the US for gout in the last 40 years. A num ber of re cent drugs have been de nied ap - 

proval. For ex am ple, an other XAO oxypurinol (allopurinol’s ac tive me tab o lite) Oxyprim was be ing de vel - 

oped by Cardiome (Can ada) for use in gout and con ges tive heart fail ure but this was as so ci ated with a 

num ber of deaths and did n’t get past the ar thri tis ad vi sory com mit tee in 2004. Merck & Co had hoped to 

gain an in di ca tion in gout for its COX-2 in hib i tor Arcoxia (etoricoxib) but the NDA was re jected by the 

FDA in 2007 due to associated cardiovascular risk. 

An a lyst at Mor gan Stan ley con sider that febuxostat of fers a mean ing ful al ter na tive for gout treat ment to 

the cur rent stan dard. It could ben e fit re nal pa tients due to be ing ex creted pre dom i nantly via the liver 

(ver sus re nal ex cre tion for allopurinol). Febuxostat (80mg) has also shown good ef fi cacy with 25-38% 

more pa tients reach ing less than 6mg/dl sUA than allopurinol with the 40mg dose show ing 20-22% 

higher pa tients achiev ing these lev els; both doses showed en hanced ef fi cacy in pa tients with 

mild-to-mod er ate re nal im pair ment. Fur ther more, the CON FIRMS study did not show any in creased car - 

dio vas cu lar events were than with allopurinol. 

The de ci sion on febuxostat could af fect other gout ther a pies in de vel op ment. The next clos est to mar ket 

is Savient’s pegloticase, a pegylated mam ma lian urate oxidase un der de vel op ment for the treat ment of 

hyperuricemia in pa tients who have failed to nor mal ize se rum uric acid lev els with con ven tional ther apy 

or for whom con ven tional ther apy is con tra in di cated; the com pany hopes to file dur ing 2009 but it has 

shown some car dio vas cu lar ad verse events and in fu sion re ac tions. Pfizer has also an nounced plans to 

sub mit its COX-2 inhibitor Celebrex for gouty arthritis. 



Sales/An a lysts Com ment: An a lysts at Mor gan Stan ley (Au gust 2008) fore cast first year sales of 

Yen10.5 bil lion in the year end ing March 2010, ris ing to Yen36.8 bil lion by fis cal 2012 (end ing March 

2013). 

TAK 783, an orally ad min is tered T-cell func tion reg u la tor, is a po ten tial treat ment for rheu ma toid ar thri - 

tis. The com pound was re ported to be in phase II de vel op ment in the EU and the USA and phase I in Ja - 

pan in 2009 with Takeda. 

TAK 715, a P38 MAP kinase in hib i tor for the po ten tial treat ment of rheu ma toid ar thri tis (RA). It was in 

phase II tri als in the USA and the EU and in phase I tri als in Japan. 

MLN 3701, an oral chemokine re cep tor 1 (CCR1) an tag o nist for the po ten tial treat ment of in flam ma tory 

dis eases such as rheu ma toid ar thri tis and mul ti ple scle ro sis was un der go ing phase I eval u a tion in the US 

in 2009 with Mil len nium (now Takeda). 

XEN 401, a COX in hib i tor, is in pre clin i cal de vel op ment for the treat ment of in flam ma tory, neuropathic, 

post-sur gi cal and mus cu lar pain. Pre clin i cal stud ies are on go ing in Can ada. In 2008, Takeda con firmed 

that prep a ra tion for clin i cal trials was ongoing. 

Li cens ing: In Oc to ber 2006, Xe non (Can ada) en tered into an ex clu sive li cens ing agree ment with Takeda 

for the de vel op ment and com mer cial iza tion of oral for mu la tions of XEN 401 in Ja pan and cer tain other 

Asian coun tries. Xe non will re ceive a $75 mil lion upfront fee, and will be el i gi ble to de vel op ment, reg u la - 

tory and sales-based mile stone pay ments. Takeda will buy $5 mil lion in Xe non stock and will pay Xe non 

roy al ties on all prod uct sales. Takeda has an op tion to back-up compounds to XEN 401 developed by 

Xenon. 

AMG 108, a monoclonal an ti body that blocks the ac tion of interleukin-1 (IL-1), for the po ten tial treat - 

ment of osteoarthritis was in phase II with Amgen in 2008. IL-1 is thought to be in volved in the joint de - 

struc tion as so ci ated with osteoarthritis. In Feb ru ary 2008 Amgen and Takeda signed an agree ment 

un der which Takeda will de velop and com mer cial ize in Ja pan up to 13 of Amgen’s early- to mid clin i - 

cal-stage can di dates, including AMG 108. 

Respiratory System Agents 

asthma and allergic rhinitis therapy MLN 6095 R3X Preclinical 

MAb, interleukin-4/interleukin-13, Amgen AMG 317 R3X Preclinical 

MLN 6095, a small mol e cule in hib i tor of a tar get that has a key role in in flam ma tory dis ease is be ing de - 

vel oped for the po ten tial treat ment of asthma and al ler gic rhi ni tis. MLN 6095 was un der go ing pre clin i cal 

stud ies in the USA with Mil len nium (now Takeda) in 2008. 

AMG 317, a monoclonal an ti body that blocks the ac tions of interleukin-4 and interleukin-13, for the po - 

ten tial treat ment of asthma is un der go ing phase II eval u a tion in the US with Amgen in 2008. In Feb ru ary 

2008 Amgen and Takeda signed an agree ment un der which Takeda will de velop and com mer cial ize in Ja - 

pan up to 13 of Amgen’s early- to mid clin i cal-stage can di dates, in clud ing AMG 317. 



Systemic Anti-Infective Agents 

epetirimod TAK 851, R 851 J5B II 

CCR5 antagonist — J5C9 I 

ceftaroline TAK 599, PPI 0903 J1D Preclinical 

vaccine, acellular pertussis, tetanus, 

diphtheria, poliovirus, Takeda TAK 361S J7B1 Preclinical 

R 851, an im mune re sponse mod i fier (IRM) mol e cule, was in phase II tri als in the USA and Eu rope in 

2008 as a ther apy for cer vi cal hu man papilloma vi rus (HPV) in fec tion and cer vi cal dysplasia. Cer vi cal 

dysplasia is ab nor mal cell growth on the cer vix, usu ally caused by strains of HPV, and is the first stage 

pre ced ing the de vel op ment of cer vi cal can cer, al though not all cer vi cal dysplasia becomes cancerous. 

Li cens ing: In 2005, orig i na tor 3M (USA) and Takeda en tered into an ex clu sive co-de vel op ment and joint 

mar ket ing agree ment for R 851. Un der the terms of the deal, 3M and Takeda will share de vel op ment 

costs. Upon suc cess ful clin i cal de vel op ment and reg u la tory ap prov als, both com pa nies will jointly com - 

mer cial ize the prod uct in the USA and Eu rope. Takeda has ex clu sive rights in Ja pan and cer tain Asian 

coun tries, and 3M will have ex clu sive com mer cial iza tion rights in the rest of the world. In March 2007 this 

agree ment was up dated granting Takeda full rights to the drug from 3M. 

A CCR5 an tag o nist, be ing de vel oped as an HIV en try in hib i tor, was in phase I tri als in Ja pan. Takeda 

pre sented pre clin i cal data at the 229th Amer i can Chem i cal So ci ety na tional meet ing, March 2005, San 

Diego, USA. 

Li cens ing: In Au gust 2007, Tobira (USA) ac quired ex clu sive world wide rights from Takeda to de velop, 

man u fac ture and com mer cial ize TAK 220 and TAK 652. Fur ther de tails of the agree ment were not dis - 

closed. Both agents are orally avail able CCR5 an tag o nists with po ten tial for the treat ment of HIV in fec - 

tion. TAK 220 and TAK 652 are un der phase I eval u a tion in Eu rope and the USA. Tobira plans to start 

phase II tri als of TAK 652, with TAK 220 being developed as a back-up. 

CEFTAROLINE (TAK 599/PPI 0903) is a cephalosporin an ti bi otic, in de vel op ment for the treat ment of in - 

fec tions caused by methicillin re sis tant Staph y lo coc cus aureus (MRSA), pen i cil lin-re sis tant Strep to coc cus 

pneumoniae and Haemophilus influenzae. It is an N-phosphono prodrug of the cephalosporin de riv a tive T 

91825. Pre clin i cal mon key and rat stud ies have dem on strated bac te ri cidal activity against MRSA. 

Li cens ing: In 2003, Pen in sula li censed rights from Takeda to de velop and com mer cial ize ceftaroline in 

all world wide ter ri to ries ex cept Ja pan. Cerexa (part of For est) is now de vel op ing the prod uct, now in 

phase III trials globally. 

TAK 361S, a vac cine for the pre ven tion of po lio my eli tis, per tus sis, tet a nus and diph the ria was in pre clin i - 

cal eval u a tion in Ja pan with Takeda in 2008. 

Discontinued Compounds 

De vel op ment of the fol low ing has been dis con tin ued: 

LAPAQUISTAT (TAK 475), a squalene synthase in hib i tor, was in phase III tri als with Takeda in the USA 

and Eu rope, and phase II in Ja pan, in 2008 for the treat ment of hyperlipidemia. In March 2008 how ever, 

Takeda an nounced that de vel op ment had been dis con tin ued; based on a judg ment that the safety and 

ef fi cacy pro file of the com pound was not su pe rior to ex ist ing mar keted drugs. This fol lowed a rec om - 

mended sus pen sion of tri als us ing higher dos ages of the drug as well as ad di tional clin i cal tri als in Oc to ber 

2007 by the FDA fol low ing the emer gence of safety is sues re lat ing to liver func tion (transaminase el e va - 



tion). This had been one of three drugs crowned by Takeda as ‘jew els’ in the pipe line and an tic i pated to 

plug the loom ing sales gap from pat ent expiration of core products in the coming years. 

MATUZUMAB (EMD 72000), a hu man ized monoclonal an ti body tar geted to epi der mal growth fac tor re - 

cep tor (EGFR) was in phase II tri als in the US, Eu rope and Ja pan with Takeda for colorectal can cer, 

nonsmall cell lung can cer (NSCLC), and gas tric can cer in 2007. In Feb ru ary 2008, Takeda and Merck 

KGaA an nounced the dis con tinu a tion of the de vel op ment of matuzumab for the treat ment of can cer af ter 

it did not meet its pre de fined endpoints of activity. 

ARXXANT (ruboxistaurin,) a pro tein kinase C beta (PKCb) in hib i tor, orig i nally de vel oped by Lilly (USA) 

was in phase II de vel op ment with Takeda and Lilly in Ja pan. In Au gust 2007 Lilly and Takeda an nounced 

that they have ter mi nated their agree ment signed in De cem ber 2003 to jointly de velop and mar ket 

ruboxistaurin in Ja pan. The de ci sion fol lowed an anal y sis of the over all re sults from di a betic pe riph eral 

neu rop a thy and di a betic macular edema phase II tri als, which did not meet their pre-spec i fied go/no go 

decision criteria for phase III trials. 

TAK 375 was in phase III tri als for Alz hei mer’s sleep/wake up dis tur bance. This study was dis con tin ued 

in 2007 how ever af ter the num ber of en rolled pa tients meet ing in clu sion cri te ria did not reach an ex - 

pected level. In 2003, re sults from early stage tri als dem on strated that TAK 375 is a highly se lec tive ML-1 

re cep tor ag o nist. A month later, Takeda pre sented data from a phase I study eval u at ing the safety, 

pharmacokinetics and pharmacodynamics of a sin gle oral dose of its melatonin ag o nist. In a study on 60 

adults re ceiv ing a dose rang ing from four to 64 mg, the fre quency of ad verse events was similar for TAK 

375 and placebo. 



Financial Data 

Key Figures 

Share Data: Shares are quoted on the Lon don, Osaka, To kyo, Nagoya, Fukuoka, Hi ro shima, Sapporo 

and Niigata Stock Ex changes. 

Key Fig ures: Key Fig ures (Con sol i dated) for years end ing March 31: 

Unit: Yen bil lions, ex cept EPS in Yen 

2008 2007 2006 2005 2004 

Sales 1,374.8 1,305.2 1,212.2 1,123.0 1,086.4 

R&D 275.8 193.3 169.6 141.5 129.7 

Pre-tax Profit 576.8 625.4 518.0 441.1 446.1 

Net Profit 355.5 335.8 313.2 277.4 285.3 

Earnings per Share (Yen) 419.0 386.0 353.5 313.01 321.9 

Current Assets 2243.8 2,357.7 2,372.0 1,969.9 1,730.1 

Fixed Assets 605.5 714.8 670.3 575.5 605.5 

Total Assets 2,849.3 3,072.5 3,042.3 2,545.4 2,335.7 

Total Liabilities 526.7 611.4 646.7 499.2 512.2 

Shareholders’ Equity 2,314.2 2,216.7 2348.4 2,001.4 1,781.0 


Sales by Business Sector for years ending March 31: 

Unit: Yen bil lions 

2008 2007 2006 2005 2004 

Pharmaceuticals 1,272.1 1,202.8 1,074.5 970.5 935.3 

Other* 102.7 102.4 137.7 152.5 151.1 

TOTAL 1,374.8 1,305.2 1,212.2 1,123.4 1,086.4 


*Note: Seg ment clas si fi ca tions were re vised dur ing FY2003, the re sults of which were ret ro ac tively re - 

stated. 



Sales by Geographical Region for years ending March 31: 


2008 2007 2006 2005 2004 

Japan 859.3 661.7 675.1 644.5 624.5 

North America 357.9 426.6 335.9 287.4 296.0 

Europe 147.3 192.0 180.2 171.6 147.3 

Asia/Other Markets 10.3 25.0 21.0 19.4 18.6 

TOTAL 1,374.8 1,305.2 1,212.2 1,123.4 1,086.4 




Analyst Figures 

Financial analysts have provided the following forecasts for Takeda: 

CREDIT SUISSE (February 2009) 

Key Figures for years ending March 31: 


2008(A) 2009(E) 2010(E) 20011(E) 

Net Sales 1,374.8 1,570.0 1,610.0 1,620.0 

Net Profit 355.5 200.0 245.0 265.0 

Operating Profit 423.1 280.0 390.0 420.0 

EPS (Yen) 418.97 244.34 299.32 323.75 

MORGAN STANLEY (February 2009) 

Key Figures for years ending March 31: 


2008(A) 2009(E) 2010(E) 20011(E) 2012(E) 2013(E) 

Net Sales 1,374.8 1,560.0 1,600.0 1,700.0 1,650.0 1,640.0 

Net Profit 355.5 210.0 291.0 344.0 322.0 337.0 

Pre-tax Profit 576.8 388.0 460.0 543.0 525.0 530.0 

R&D 275.8 460.0 340.0 345.0 330.0 330.0 

EPS (Yen) 417.63 257.32 371.59 446.40 437.93 451.98 



MORGAN STANLEY (August 2008) 

Sales of Leading Parent Company Products for years ending March 31 


Product 2008(A) 2009(E) 2010(E) 2011(E) 2012(E) 2013(E) 

Actos 396.2 414.0 467.0 513.5 371.0 321.5 

-Japan 41.6 50.0 57.0 63.0 70.0 70.0 

-USA 318.6 320.0 357.0 388.5 231.0 178.5 

-Europe 32.5 40.0 48.0 56.0 63.0 65.0 

-Export 62.0 61.2 68.9 75.6 50.0 41.4 

-Royalty 22.5 25.2 28.4 31.1 20.6 17.0 

Takepron (consolidated) 148.7 301.1 288.0 223.0 224.0 224.0 

-Japan 64.8 68.0 74.0 77.0 80.0 82.0 

-USA 256.2 178.3 105.0 0 0 0 

-Europe 35.8 30.0 25.0 22.0 20.0 18.0 

-Asia 4.0 4.2 4.4 4.0 3.5 3.5 

-Export (parent) 65.0 44.6 28.2 5.2 4.7 4.3 

-Royalty (parent, including TAK 390)23.0 14.9 8.7 1.6 1.4 1.3 

TAK 390 (USA) — 21.0 80.0 120.0 120.0 120.0 

TAK 390 (exports) — — 15 22 22 22 

Blopress 223.1 228.5 245.0 259.0 263.0 246.5 

-Japan 137.1 135.0 145.0 152.0 160.0 170.0 

-Overseas 86.0 93.5 100.0 107.0 103.0 76.5 

-Export 45.0 46.5 49.0 51.0 49.0 34.0 

-Royalty 6.0 6.9 7.2 7.6 7.2 5.1 

Leuprin (consolidated) 124.0 125.0 122.5 119.5 116.0 112.5 

-Japan 66.4 65.0 65.0 65.0 65.0 65.0 

-USA 73.7 66.1 63.0 57.8 52.5 47.3 

-Europe 40.2 40.0 38.0 36.0 34.0 32.0 

-Asia 4.0 4.5 5.0 5.0 5.0 5.0 

-Export 36.0 33.2 31.8 29.6 27.5 25.3 

-Royalty 6.0 5.0 4.8 4.4 4.1. 3.8 

Basen 52.8 47.0 45.0 42.0 40.0 37.0 

Amitiza 19.5 23.1 26.3 29.4 33.1 36.8 

Enbrel 18.8 30.0 35.0 38.0 42.0 45.0 

Benet 16.5 17.5 20.0 22.0 24.0 26.0 

Rozerem 12.6 9.4 10.5 21.5 27.5 33.5 

-USA 12.6 9.4 9.5 9.5 9.5 9.5 

-Europe 0 0 1 2 3 4 

-Overseas 12.6 9.4 10.5 11.5 12.5 13.5 

-Export 2.5 1.7 1.9 1.8 1.9 2.0 

-Royalty 1 1 1 1 1 1 

Isovorin 12.5 10.5 10.0 10.0 10.0 10.0 



Seltouch 12.3 12.0 12.0 12.0 12.0 12.0 

Glovenin 8.8 8.5 8.5 8.5 8.5 8.5 

Pansporin 8.4 7.5 7.0 7.0 7.0 7.0 

Dasen 7.7 7.5 7.5 7.0 7.0 7.0 

Firstcin 6.4 6.0 6.0 6.0 6.0 6.0 

Calsot 5.0 4.0 4.0 3.5 3.5 3.5 

Glufast 3.2 4.5 6.0 8.0 10.0 12.0 

Velcade 30.3 36.5 47.3 57.8 68.3 76.7 

Other Millennium Revenue 30.0 22.1 23.5 24.5 25.4 26.2 

OTC (Total) 61.8 60.0 60.0 60.0 60.0 60.0 

-Alinamin 35.0 15.0 15.0 15.0 15.0 15.0 

-Alinamin V drinks 32.0 12.0 12.0 12.0 12.0 12.0 

-Benza 10.0 8.5 8.5 8.5 8.5 8.5 

-Nicorette 10.0 4.0 4.0 4.0 4.0 4.0 

-Others — 20.5 20.5 20.5 20.5 20.5 

TMX 67 — — 10.5 21.0 31.5 36.8 

SYR 322 — — 42.0 84.0 136.0 187.5 

-USA — — 42.0 84.0 126.0 157.5 

-Europe — — 0 0 10.0 30.0 

-Overseas — — 42.0 84.0 136.0 187.5 

-Export — — 7.6 15.1 24.5 33.8 

-Royalty — — 2.9 5.9 9.5 13.1 



IMS Sales Data 

Pharmaceutical Sales by Geographical Region and Leading Countries 

Country Share 

of Regional 

Corporate Sales 

% 

Percentage 

Growth Sep 

07/Sep 08 

USD USD FIXED 

RATE 

TOTAL SALES 100.0 10 5 

NORTH AMERICA 55.6 5 5 

U.S.A. 100.0 5 5 

ASIA, AFRICA & AUSTRALASIA 33.7 16 6 

JAPAN 96.0 16 5 

THAILAND 1.3 33 27 

TAIWAN 1.2 13 7 

INDONESIA TOT MKT 0.5 17 19 

CHINA HOSPITAL 0.3 13 4 

EUROPE 10.1 17 5 

FRANCE 26.8 3 -9 

GERMANY 26.1 21 7 

ITALY 19.6 20 6 

UNITED KINGDOM 14.8 38 38 

AUSTRIA 4.7 23 8 

LATIN AMERICA 0.6 18 18 

PUERTO RICO 100.0 18 18 

DOMINICAN REP RET 0.0 -25 -22 

The com pany’s phar ma ceu ti cal sales are an a lyzed in terms of geo graph ical re gion, and within each re - 

gion the ma jor coun tries pre sented. Sales data cov ers the twelve months to Sep tem ber 2008. See Ap - 

pen dix for coun try universe sourced. 

Sales and growth for the au dited Latin Amer i can coun tries are pre sented in US dol lars only. The de ci sion 

for con ver sion to US dol lars was due to ex ces sive in fla tion and sub se quent de val u a tions lead ing to both 

lo cal cur rency and ex change rates ex ceed ing the field sizes avail able for them on the MIDAS database. 

� Takeda Total Sales by Top Five Markets 

Source: IMS Health 

France 

3% 

Germany 

3% 

Japan 

32% 

Italy Others 

2% 5% 

Sales by Top 5 Markets 

USA 

55% 



Pharmaceutical Sales by Country and Subsidiary 

Share of 

Regional 


% 

Percentage 

Growth Sep 

07/Sep 08 

USD USD FIXED 

RATE 


U.S.A. 55.6 5 5 

TAKEDA PHARM USA 95.6 3 3 

MILLENNIUM PHARM 4.4 39 39 

JAPAN 32.4 16 5 

TAKEDA YAKUHIN KOG 96.5 16 5 

NIHON SEIYAKU TOKY 3.3 13 2 

WAKO JUNYAKU KOGYO 0.1 21 9 

NIHON SEIYAKU KOGY 0.0 8 -2 

FRANCE 2.7 3 -9 

TAKEDA S.A. 100.0 3 -9 

GERMANY 2.6 21 7 

TAKEDA PHARMA 100.0 21 7 

ITALY 2.0 20 6 

TAKEDA ITALIA FARM 100.0 20 6 

UNITED KINGDOM 1.5 38 38 

TAKEDA 100.0 38 38 

PUERTO RICO 0.6 18 18 

TAKEDA PHARM USA 99.1 18 18 

MILLENNIUM PHARM 0.9 -9 -9 

AUSTRIA 0.5 23 8 

TAKEDA PHARMA 100.0 23 8 

This ta ble shows the break down of the com pany’s phar ma ceu ti cal sales in terms of lead ing coun tries and 

sub sid iar ies. Sta tis tics for coun try share of cor po rate rev e nue, sub sid iary share of coun try rev e nue, US 

dol lar and US dol lar fixed rate growth over the pre vi ous twelve month pe riod are pre sented. Sales data 

cov ers the pe riod for the twelve months to September 2008. 

All of the sub sid iar ies men tioned above are 100%-owned by Takeda ex cept Nihon Seiyaku Kogy and 

Nihon Seiyaku Toky (both 82%-owned by Takeda); Takeda Italia Farm (77%-owned by Takeda) and 

Wako Junyaku Kogy (31%-owned by Wako Junyaku Kogyo). Sales for a sub sid iary are al lo cated to the 

cor po ra tion with the ma jor ity shareholding. In re la tion ships where there is a 50:50 shareholding, how - 

ever, sales will con tinue to be split 50:50 be tween the two own ing corporations. 



Pharmaceuticals: Top Five Third Level Therapeutic Classes 

ATC Therapeutic 

Class 

Description 

US 

Dollar 

Sales 

(‘000s) 

Share of 

Worldwide 


% 

Percentage 

Growth Sep 

07/Sep 08 

USD USD FIXED 

RATE 

TOTAL SALES 13722422 100.0 10 5 

1 A10B ORAL ANTIDIABETICS 4576045 33.3 14 11 

2 A2B ANTIULCERANTS 4550938 33.2 -1 -3 

3 C9C ANGIOTEN-II ANTAG, PLAIN 1506973 11.0 17 6 

4 L2A CYTOSTATIC HORMONES 789109 5.8 12 1 

5 L1X ALL OTH. ANTINEOPLASTICS 344256 2.5 39 39 

This ta ble shows the com pany’s top five third level ther a peu tic classes. Sales data cov ers the twelve 

month pe riod to Sep tem ber 2008. Sta tis tics for third-level ther a peu tic class share of cor po rate rev e nue, 

US dol lar and US dol lar fixed rate growth over the pre vi ous twelve month pe riod are presented. 

The lead ing five ther a peu tic classes ac count for 85.8% of cor po rate rev e nue. 

Pharmaceuticals: Leading International Products 

International 

Products 

Share of 

Worldwide 


% 

Percentage 

Growth Sep 

07/Sep 08 

USD USD FIXED 

RATE 


1 TAKEPRON 32.1 -1 -3 

2 ACTOS 26.7 12 10 

3 BLOPRESS 11.0 17 6 

4 ENANTONE 6.3 13 1 

5 BASEN 3.1 3 -6 

6 ACTOPLUS MET 3.0 56 55 

7 VELCADE 2.5 40 40 

8 AMITIZA 1.4 66 66 

9 BLOPRESS COMP 1.3 20 7 

10 PREVPAC 1.0 -0 -1 

This ta ble shows the com pany’s lead ing ten phar ma ceu ti cal prod ucts. For each prod uct, its per cent age 

share of cor po rate rev e nue and US dol lar and US dol lar fixed rate growth are shown. In this study, in ter - 

na tional prod ucts are used. The con cept of the in ter na tional prod uct was de vised for IMS’s in ter na tional 

da ta base MI DAS, to en able us ers to eval u ate sales of a prod uct in ter na tion ally, even if the prod uct is 

known by dif fer ent names in dif fer ent coun tries. Prod ucts are linked in ter na tion ally if at least two of the 

fol low ing three char ac ter is tics are the same as in coun try of first launch: brand name; marketing 

corporation; active ingredients. 

The top ten in ter na tional prod ucts ac counted for 88.4% of cor po rate rev e nue. 



Pharmaceutical Sales Analysis By Product Age 

US 

Dollar 

Sales 

(‘000s) 

Share of 

Worldwide 


% 

Percentage 

Growth Sep 

07/Sep 08 

USD USD FIXED 

RATE 

TOTAL SALES 13722422 100.0 10 5 

PRODS 1-2 YEARS 94925 0.7 230 216 

PRODS 3-5 YEARS 929689 6.8 40 36 

PRODS 6-10 YEARS 6141302 44.8 16 11 

PRODS 11 YEARS 6556506 47.8 1 -4 

This ta ble an a lyzes com pany sales by prod uct age, as sess ing sales in terms of new prod ucts, es tab lished 

prod ucts, ma ture prod ucts and old prod ucts. A new prod uct is de fined as a new launch of an ex ist ing 

prod uct, a new chem i cal en tity or a com bi na tion prod uct in an in di vid ual coun try over the last two years 

to September 2008. 



Appendix 

All ta bles in this sec tion are based on the fol low ing coun try uni verse. Al though all uni verse coun tries 

are se lected, in di vid ual cor po ra tions may not op er ate in all mar kets. In most cases, sales data cov ers 

the twelve-month pe riod to September 2008. 

Audited Universes 

North America Europe Asia, Africa & Australasia Latin America 

Canada* Austria* Algeria Argentina 

United States** Belgium* Australia* Brazil 

Belorussia Bangladesh Central America*** 

Bulgaria* China Hospital Chile 

Croatia Egypt Colombia 

Czech Republic* French W Africa Dominican Republic 

Denmark Hong Kong Ecuador 

Finland* India Mexico 

France* Indonesia* Peru 

Germany* Israel Puerto Rico* 

Greece Japan* Uruguay 

Hungary* Jordan Venezuela 

Ireland Korea* 

Italy* Korea Clinic 

Latvia* Kuwait 

Lithuania* Lebanon 

Luxembourg Malaysia 

Netherlands Xponent Morocco 

Norway New Zealand* 

Poland* Pakistan 

Portugal Philippines* 

Russian Federation* Saudi Arabia 

Spain* South Africa* 

Slovak Republic* Singapore 

Slovenia Taiwan* 

Sweden Thailand* 

Switzerland* Tunisia 

Ukraine Turkey* 

United Kingdom* United Arab Emirates 

*Note: In cludes hos pi tal sales in ad di tion to re tail sales. 

**Note: USA in cludes hos pi tal, clinic and mail or der sales, re tail sales, HMO, long term care, home health 

care, foodstore and ‘mis cel la neous’ sales (pris ons, uni ver si ties etc). 

***Note: Cen tral Amer ica = Costa Rica, Gua te mala, Hon du ras, El Sal va dor, Nic a ra gua and Panama. 



Employee Data 

The company had the following number of employees (consolidated) for years ending March 31: 

2004 14,592 

2005 14,510 

2006 15,069 

2007 14,993 

2008 15,717 




Licensing/Co-Marketing Agreements 

Marketed Products 

Product Class Date Terms of Agreement 

Lialda (mesalamine) A 2008 Shire and TAP (dissolved in May 2008) to copromote 

Lialda (for ulcerative colitis) in the US under 3-yr 

agreement. 

Provigil (modafinil) N 2006 Cephalon and Takeda entered into an agreement under 

which Takeda will co-promote Provigil in the USA. The 

three-year deal will have an option to renew annually. 

Cephalon will pay Takeda a royalty based on certain sales 

criteria for both products. Cephalon will retain all 

responsibility for development, distribution and sales of 

modafinil. 

Prevacid (lansoprazole) A 2006 TAP has granted Novartis the right to develop an OTC 

version of Prevacid in the US. Novartis will take full 

responsibility for the switch-OTC program, including the 

design and conduct of clinical studies, regulatory 

submissions to the FDA and manufacturing, distribution 

and launch activities. Financial arrangements were 

undisclosed. 

Glufast (mitiglinide) A 2004 Kissei will co-market the agent in Japan in collaboration 

with Takeda. Licensee Servier acquired rights to develop 

this agent in Europe, the Middle East, Africa, Oceania, 

and Asian countries, excluding Japan, China, Taiwan, and 

Korea. 

Actos A 2004 Takeda and Andrx agreed to co-develop a product 

combining Actos with Andrx’s Fortamet (metformin 

extended release).Once approved, it will be 

manufactured by Andrx. Exclusive marketing rights will 

be held by Takeda, which will be responsible for 

approvals. Andrx will receive $10 million as an initial 

payment, and be eligible for additional milestone, royalty 

and performance payments. 




Niaspan (niacin)/Advicor 

(niacin/lovastatin) 

Leuplin /Lupron Depot 

(leuprorelin) 

C 2003 Takeda signed an agreement with Kos to co-promote 

both products in the USA from January 2004. The deal 

between TPNA and Kos will last three years, but can be 

extended. If the companies do not renew the 

partnership, Takeda will be eligible to receive declining 

tail payments for a period of three years following 2006. 

Under the agreement, Takeda’s US salesforce will 

co-promote the products and Takeda will receive an 

undisclosed percentage of net sales for the Kos’s current 

cholesterol franchise above a specific baseline level. 

L 2003 TAP obtained an exclusive license from Norwood Abbey 

to expand the indications for Lupron, by using intellectual 

property owned by Norwood. The two companies will 

jointly fund R&D to assess several applications in fields, 

with TAP taking responsibility for filing any resulting 

sNDAs. TAP would be eligible to pay milestones and 

royalties to Norwood, and has acquired a $2 million 

equity stake in Norwood Immunology, a wholly-owned 

Norwood subsidiary. 

NovoNorm (repaglinide) A 2003 Licensed in from Novo Nordisk for co-marketing in Japan. 

Gasmotin (mosapride) A 2003 Licensed from Dainippon Sumitomo for worldwide 

development and marketing, excluding Japan, China, 

Taiwan and South Korea. 

Prepenon Takeda 

(injectable liquid 

morphine hydrochloride) 

Actos (pioglitazone) A 1998/ 

2000 

N 2000 Partnership with Terumo. Terumo will develop and 

produce the product. Takeda began selling it in 2001. 

In the US, Actos is co-promoted by Lilly. In Japan, 

Takeda co-markets pioglitazone with Novo Nordisk. 

Abbott has exclusive rights in nine Latin American 

countries. In October 2004, TPNA filed through Takeda 

Global Research & Development Center an NDA for 

Actoplus Met (combination drug of pioglitazone and 

metformin) with the FDA as a treatment for type 2 

diabetes. 

Flomax (tamsulosin) G 1997 Yamanouchi (now Astellas) granted Takeda co-promotion 

rights in Japan to tamsulosin, an oral alpha1 antagonist, 

which has been launched worldwide for the treatment of 

benign prostatic hypertrophy (BPH) and urinary tract 

disorders. In June 2007, Astellas submitted tamsulosin 

for approval in Japan for lower urinary tract syndrome in 

male patients. 




Spectracef (cefditoren 

pivoxil) 

J 1997 TAP licensed-in exclusive rights to cefditoren pivoxil in 

North America from originator Meiji Seika. In 1999, 

Abbott obtained exclusive rights in Latin America, plus 

co-marketing rights in Europe (with Gruenenthal) and an 

option for the product in Asian countries outside Japan. 

However, Takeda and Abbott have now withdrawn from 

this deal. 

Benet (risedronic acid) M 1992 Originally developed by Procter & Gamble and licensed to 

Ajinomoto for Japan. It was then co-developed with 

sub-licensees Takeda and Aventis, following an 

agreement between P&G and Aventis to market the 

product worldwide. 

Basen (voglibose) A N/A Licensed out to Cheil for South Korea. 

Takepron (lansoprazole) A N/A Marketed by TAP jv with Abbott in the US, and by Takeda 

Pharma in German-speaking markets. Licensed out to 

Abbott for Canada and Latin America and to Boehringer 

Ingelheim and Roemmers for some Latin American 

countries. Almirall Prodesfarma for Spain. Wyeth for the 

UK, Denmark, Australia, Sweden, Norway and Pakistan. 

Aventis for France, Germany, the NL, Belgium, Africa and 

the Middle East. To Orion for Finland. To Han Il for South 

Korea. 

Blopress (candesartan 

cilexetil)/Blopress Comp 

(candesartan 

cilexetil/hydrochlorothiazi 

de) 

Uprima/Ixense (sublingual 

apomorphine) 

Adecut/Cupressin 

(delapril) 

C N/A Licensed out to AstraZeneca for exclusive marketing in 

Belgium, Denmark, Finland, the Netherlands, Norway, 

New Zealand, Australia, and South Africa, and 

co-marketing in the rest of the world outside Japan. 

Licensed out to Teva for Israel, Orion for Ireland, Almirall 

Prodesfarma for Spain, Abbott for co-marketing in 

Mexico, Brazil, and Argentina with AstraZeneca, and in 

Chile with Saval. 

G N/A Takeda has licensed-out the product to TAP for the USA. 

TAP has in turn licensed it out to Abbott for other 

markets. TAP holds exclusive worldwide rights to 

apomorphine for the treatment of Parkinson’s Disease. 

C N/A Licensed-out to Chiesi for Italy. 

Acel-Imune (DTP vaccine) J N/A Licensed out to Lederle-Praxis Biologicals (Wyeth) for 

markets outside Japan. 




Takesulin (cefsulodin) J N/A Licensed out to Novartis for co-marketing in Japan and 

for marketing and co-marketing in certain other non-US 

markets. Licensed out to Abbott for Canada. Marketed in 

Germany and Austria by Takeda Pharma. 

Firstcin (cefozopran), J N/A Co-launched in Japan in 1995 by originator Takeda and 

licensee Lederle (Wyeth). 

Pansporin T (cefotiam 

hexetil), 

J N/A Co-marketed in France with Aventis. Cheil is the licensee 

for South Korea. 

Pansporin (cefotiam) J N/A Licensed out to Novartis for a number of markets outside 

Japan. Han Il is the licensee for South Korea. 

Bestcall (cefmenoxime) J N/A Co-marketed in Japan with licensee Roche. Han Il is the 

licensee for South Korea. Marketed in Germany by 

Takeda Pharma. 

Canferon-A (interferon 

alfa-2a) 

Leuplin/Lupron Depot 

(leuprorelin) 

L N/A Jointly developed with Roche under license from 

Genentech and co-marketed with Roche in Japan. Roche 

markets it worldwide (including Japan) as Roferon-A. 

L N/A Licensed out to Abbott for Canada, Europe, Mexico and 

several other Latin American countries. TAP markets it in 

the US, and Takeda Pharma in Germany and Austria. The 

drug is also marketed for precocious puberty in Germany, 

Italy and France, and for breast cancer in Japan, Italy 

and France. 

Osten (ipriflavone) M N/A Licensed in from Chinoin (now part of Sanofi-Synthelabo) 

for Japan and for co-marketing in Italy. 

Anpec Takeda (morphine 

hydrochloride) 

MS Contin Takeda 

(morphine sulfate) 

N N/A Co-developed and co-launched in Japan with Sankyo, 

Shionogi and Dainippon. 

N N/A Licensed in from Mundipharma and co-developed and 

co-launched in Japan with Sankyo, Shionogi and 

Dainippon. 



R&D Pipeline Products 


GVAX V/L 2008 Cell Genesys licensed ww rights of GVAX 

(immunotherapy of allogeneic cancer cell lines, modified 

to secrete GM-CSF (granulocyte macrophage-colony 

stimulating factor ) for prostate cancer to Takeda for 

$50m upfront and milestones of up to $270m in the USA, 

EU and Japan in addition to royalties. Takeda will pay all 

ongoing development and commercialization costs with 

Cell Genesys responsible for ww manufacture and supply, 

while retaining rights to co-promote GVAX for prostate 

cancer in the USA. In December 2008 Takeda terminated 

development with all commercial rights to be returned to 

Cell Genesys who will receive wind-down payments 

associated with the phasing out of the remaining clinical 

development activities. 

Motesanib (AMG 706) L 2008 Takeda has obtained rights from Amgen to exclusively 

develop and market the anticancer drug motesanib (AMG 

706) in Japan and co-develop and co-market with Amgen 

Inc outside of Japan. Takeda will pay $100m upfront and 

pay 100% of development in Japan and 60% overseas, 

in addition to milestone payments of up to Yen175m as 

well as royalties. 

12 compounds — 2008 Takeda has obtained exclusive rights to 12 biologic 

compounds from Amgen warranting an upfront payment 

of $2million, payment of all development costs in Japan 

as well as a percentage overseas, totaling up to $340m 

and potentially another Yen362m in milestones and then 

royalties on sales. 

TAK 652. and TAK 220 J 2007 Tobira acquired exclusive worldwide rights from Takeda 

to develop, manufacture and commercialize TAK 220 and 

TAK 652. Further details of the agreement were not 

disclosed. Both agents are oral CCR5 antagonists for HIV 

in phase I in Europe and the USA. Tobira plans to start 

phase II trials of TAK 652, with TAK 220 being developed 

as a back-up. 




LU AA21004 & LU 

AA24530 

N 2007 Co-development & co-commercialization with Lundbeck 

in the USA & Japan of several Lundbeck pipeline 

compounds for mood & anxiety disorders. Initial focus will 

be on LU AA21004 & LU AA24530, with option under 

certain conditions to include 2 other compounds of the 

same class in earlier development. If approved, both will 

co-promote in the USA & Japan. Lundbeck will receive 

initial $40m up to $345m in milestones. They will jointly 

complete development, with Takeda booking total sales & 

funding most of development. Lundbeck will receive a 

share of the revenue generated in the USA & Japan as 

well as royalty payments on Takeda’s share of revenues. 

CBP 501 L 2007 Agreement with CanBas granting Takeda exclusive rights 

to develop, manufacture and market this and backup 

cancer compounds worldwide, except in the US where 

activity will be jointly conducted. CanBas, a G2 

checkpoint abrogater (injection) is currently in a phase I 

trial in the US for malignant mesotherioma, lung cancer. 

XEN 401 M 2006 Xenon entered into an exclusive licensing agreement with 

Takeda for the development and commercialization of 

oral formulations of XEN 401 in Japan and certain other 

Asian countries. Xenon will receive a $75 million upfront 

fee, and will be eligible to development, regulatory and 

sales-based milestone payments. Takeda will also buy $5 

million in Xenon stock. Takeda confirmed preparation for 

clinical studies, ongoing in 2008. 

HuL 2G7 L 2006 Galaxy granted Takeda exclusive, worldwide rights to 

develop, manufacture and market HuL 2G7. Galaxy will 

receive an upfront $2 million licensing fee from Takeda, 

as well as milestone payments dependent on the 

achievement of certain development and regulatory 

milestones. Galaxy will also be entitled to royalties on 

product sales. 

Hematide (pegylated 

erythropoietin receptor 

agonist, Affymax) 

B 2006 Affymax initially granted Takeda rights to develop and 

commercialize Hematide in Japan. Subsequently they 

signed an agreement to collaborate on the development 

and co-commercialization of Hematide in the USA, and 

Takeda will hold an exclusive development and 

commercialization license outside the USA. Affymax is to 

receive an upfront cash payment of $105 million, as well 

as being eligible to receive development and regulatory 

milestone payments of up to $280 million, and 

commercialization milestone payments of $430 million. 




Omacor (TAK 085) A 2005 Takeda licensed the Japanese rights to Omacor from 

Pronova. 

Matuzumab L 2005 Takeda signed a co-development and co-promotion 

agreement for matuzumab with originator Merck KGaA in 

September 2005. 

Ilaprazole A 2005 Il Yang licensed worldwide rights to ilaprazole, a proton 

pump inhibitor, outside South Korea and China, to TAP. 

R 851 J 2005 Collaboration to jointly develop and market 3Ms topical 

immune response modifier. Takeda has acquired 

exclusive Japan/Asia region rights. In 2007 this 

agreement was updated granting Takeda full rights to the 

drug from 3M. 

GnRH analogue, Norwood 

Immunology/TAP 

L 2005 TAP and Norwood Immunology are jointly developing 

GnRH analogues, which have potential in bone marrow 

transplants, cancer and HIV infection. 

TAK 363/TRK 130 G 2005 A compound for the treatment of urinary incontinence, 

co-developed by Takeda and Toray. Toray will market it 

in Japan and Takeda will market it in overseas territories. 

It was discovered in Toray’s compound library through 

joint research by both companies 

Idebenone N 2005 Collaborative deal with regarding development of 

Santhera’s idebenone, a small molecule with potential in 

the treatment of Friedreich’s ataxia. Santhera will 

conduct all clinical development to gain regulatory 

approval in Europe and the USA. Takeda will support 

development and obtain an exclusive marketing license in 

the EU and Switzerland. Santhera plans to market 

idebenone independently in the USA. In August 2007 

Santhera granted Takeda marketing rights in the EU and 

Switzerland to idebenone for the treatment of Duchenne 

Muscular Dystrophy (DMD). 

Amitiza (lubiprostone) A 2004 Takeda agreed to jointly market lubiprostone in the USA 

and Canada with originator Sucampo Takeda also 

acquired an option to lubipristone in other territories, 

such as Japan and Europe. 

Arxxant (ruboxistaurin) A 2003 Takeda signed an agreement with Lilly for joint 

development and co-marketing of the product in Japan. 

cetilistat (ATL 962) A 2003 Alizyme granted Takeda exclusive rights to develop, 

manufacture and market in Japan. 




TAK 599/PPI 0903 J 2003 Takeda out-licensed TAK 599 to Peninsula, for exclusive 

development worldwide, excluding Japan. Takeda will be 

responsible for manufacture, worldwide. 

LGD 2226 G 2001 Ligand granted TAP exclusive worldwide rights to 

manufacture and sell any products resulting from the 

companies’ collaboration in the field of selective androgen 

receptor modulators (SARMs), including LGD 2226, for 

the treatment of certain androgen-related diseases and 

disorders. In 2003, the companies announced plans to 

extend their research collaboration in this area for one 

year. 

Y 128 N 2001 Takeda gained exclusive worldwide development and 

marketing rights from Welfide (now Mitsubishi Pharma). 

lestaurtinib (CEP 701) L 1999 Licensed out to TAP from Cephalon for the USA. 

febuxostat (TMX 67) M 1999 Licensed in by TAP from Teijin for North America. 

asoprisnil G N/A Licensed-in by TAP from Jenapharma (now part of 

Schering AG). 



General Research Collaborations 

Company/Organization Date Area of 

Collaboration 

Terms of Agreement 

Alnylam 2008 RNAi Non-exclusive licensing deal for access to 

Alynlam RNA interference technology in 

oncology and metabolic disease signed in 

May. Deal valued at $1bn comprising 

$100m upfront in cash, $50m in 

near-term technology transfer payments 

($20m received in October 2008) and up 

to $1bn in development/commercial 

milestones and royalties ($171m per 

product). Over 5 years, Takeda becomes 

Alnylam’s strategic partner for RNAi 

therapeutics. Takeda is granted the right 

of first negotiation to develop and 

commercialize Alnylam RNAi therapeutic 

programs for the Asian market (excluding 

Alnylam’s ALN-RSV01), while Alnylam can 

opt-in to codevelop/commercialize 

Takeda’s RNAi programs in the US. 

Harvard University 2008 Oncology research Millennium signed an agreement to 

investigate pathways that regulate cellular 

protein homeostasis using a technology 

developed by researchers at Harvard 

University. These pathways are linked to 

the pathogenic properties of a range of 

cancers. Financial terms not disclosed 

Faust Pharmaceuticals 

(now Domain 

Therapeutics) 

2008 Drug discovery Research agreement with Takeda, under 

which Faust Pharmaceuticals is to use the 

NEUROCLID technology platform to 

identify drug candidates targeting 

undisclosed G-Protein Coupled Receptors 

(GPCR) for Takeda. Financial terms not 

disclosed. 

Chemizon 2008 Drug discovery Expansion to previous collaboration using 

Chemizon’s Discovery Platform. 

Curidium Medica (UK) 2007 Depression drug 

discovery 

© 2009 IMS Health In cor po rated or its af fil i ates Page 99 

Investment by Takeda Research 

Investment (TRI) in Curidium Medica 

(around 1.8%, totaling STG1.2m) in a 

deal giving access to biomarkers and drug 

targets related to depression identified 

from Curidium’s research.



Collaboration 

LG Life Sciences 2007 Obesity drug 

discovery 


Based on LG Life Sciences’ obesity 

program, the company will use its 

capabilities in drug discovery including 

medicinal chemistry and pharmacological 

evaluation; Takeda responsible for 

subsequent R&D and commercialization. 

Takeda will have exclusive rights to 

selected compounds ww excluding South 

Korea and Vietnam, with semi-exclusive 

rights in India. In return, Takeda make 

upfront, research and milestones of over 

$100m in addition to royalties on resultant 

products. In 2008 agreement ongoing and 

candidates being screened for clinical 

development. 

Biowa 2007 Antibody discovery Agreement which provides Takeda with 

access to Biowa’s (part of Kyowa Hakko) 

patented Potelligent Technology platform 

for the development of 

antibody-dependent cellular cytotoxicity 

(ADCC) enhanced antibodies. 

XOMA 2007 Antibody discovery Agreement amended to increase number 

of antibody discovery projects with 

Takeda. Xoma earned $8m so far (in 4 

months since start of collaboration) and 

estimates total R&D funding and 

payments could reach $230m over the 

course of the amended agreement. 

Confirmed ongoing in 2008 and expanded 

to grant Takeda access to multiple 

antibody technologies, paying Xoma a 

$29m expansion fee. 

Archemix 2007 Drug discovery for 

three undisclosed 

disease indications 


Agreement to collaborate on the 

discovery, development and 

commercialization of aptamer based 

therapeutics. Takeda granted exclusive 

rights for global R&D, manufacturing and 

commercialization of resultant products in 

return for $6m upfront, research funding, 

milestone and royalty payments on 

worldwide sales of aptamers 

commercialized by Takeda. Discovery 

phase evaluations are under way in the 

USA.



Collaboration 

ARIUS Research 2006 FunctionFIRST 

technology platform 

Paradigm Therapeutics 

(UK) 

2005 Drug discovery (CNS 

disorders) 


ARIUS Research signed a three-year 

collaborative agreement with Takeda to 

discover treatments for human disease 

using ARIUS’s FunctionFIRST technology 

platform. Under the terms of agreement 

Takeda will pay an upfront technology 

access fee of $2 million ($1 million each in 

cash and equity investment, respectively) 

as well as research funding for three 

years. Confirmed ongoing by Takeda in 

2008. 

3-year deal to access novel proprietary 

therapeutic targets identified by Paradigm 

for selected CNS disorders. Takeda will 

pay up-front fees and milestones totaling 

up to $18m for each product and then 

sales royalties. 

Flamel Technologies 2004 New formulations TAP licensed the worldwide rights for 

Flamel’s Micropump controlled-release 

technology for the oral administration of 

lansoprazole. TAP will pay costs of further 

development, testing, regulatory approval, 

and marketing of the new formulation. 

HTG 2004 New drug candidates HTG will use its multiplexed ArrayPlate 

technology to screen samples provided by 

Takeda and gather critical information on 

the interplay of genes in biological 

systems. HTG will deliver high-quality, 

multiplexed gene expression test results to 

assist Takeda to identify promising new 

drug candidates. Financial terms were not 

disclosed. In 2006 Array BioPharma 

advanced two lead compounds into 

preclinical studies, triggering milestone 

payments from Takeda. 




Collaboration 

Array BioPharma 2004 Diabetes and 

hypertension 


The companies will utilize the US firm’s 

technologies to develop improved 

candidate drugs based on compounds 

discovered by Takeda. The Japanese firm 

will own the intellectual property 

associated with the modified agents and 

will pay Array compensation linked to the 

latter’s contributions, as well as a fixed 

percentage of sales for any drug that 

enters the market. 

Ligand Pharmaceuticals 2004 Drug development Under the terms of the agreement, Ligand 

provided notice to TAP of its intention to 

exercise its option to select within 90 days 

one compound and a backup for 

development. TAP retains an option to 

negotiate to co-develop and co-promote 

compounds with Ligand up to the end of 

phase II. Ligand earned a $1 million 

milestone payment from TAP as a result. 

Ligand announced an extension of the 

collaboration in December 2004 through 

to June 2006. 

University of Tokyo 2004 Drug 

development/disease 

prevention 

Lectus Therapeutics 2004 Small-molecule ion 

channels 

Takeda joined a medical consortium 

(including Tanabe, AnGes MG, and 

Terumo) project which aims to provide a 

base and incubation facilities for research 

into new drugs, disease prevention, and 

health-related services. Terms of the deal 

were undisclosed at the time of writing. 

Takeda Research Investment is funding 

Lectus’ drug discovery and development 

programs. Specific terms and conditions of 

the deal were undisclosed at the time of 

writing. 

Innogenetics 2004 Alzheimer’s disease Innogenetics licensed patents rights to 

Takeda’s beta-amyloid antibodies for 

research and diagnostic use. Financial 

terms of the deal were undisclosed at the 

time of writing. 




Collaboration 


Lexicon Genetics 2004 Hypertension Lexicon will receive an upfront payment of 

$12 million from Takeda for the initial 

three-year term of the agreement. Takeda 

has the option to extend the discovery 

portion of the alliance for an additional two 

years in exchange for further committed 

funding. Takeda will make milestone 

payments for each target selected for 

development, while Lexicon will earn 

royalties on worldwide sales of 

commercialized drugs. $5m research 

milestone payment paid in 2006 when 

Takeda selected LG 474 for therapeutic 

development. 

Evotec 2003 Alzheimer’s disease Evotec and Takeda agreed a four year 

collaboration to identify and validate 

targets relating to the causes and 

progression of AD. Takeda will gain access 

to Evotec’s database of targets, and use 

Evotec’s expertise to further validate 

selected targets. Takeda will pay a Euro20 

million fee for access, research funding 

and milestone payments. Further 

milestone payments may become payable 

on successful clinical development. A 

second milestone was due in 2006. 

Kirin Brewery 2003 Cancer therapy Takeda in-licensed Kirin’s TransChromo 

Mouse technology to produce fully 

humanized MAbs against selected target 

protein antigens. Takeda will develop, 

manufacture and market any resulting 

products worldwide, in return for 

development milestone and sales royalty 

payments. No financial details were 

announced. Takeda confirmed ongoing in 

2008. 

Beth Israel Deaconess 

Medical Center 

2003 Diabetes and obesity BIDMC and Takeda signed a 3 year 

agreement worth $13.7m to investigate 

the molecular basis of diabetes and 

obesity. Takeda will have an exclusive 

option to negotiate a license to intellectual 

property derived from the collaboration 

and BIDMC will gain access to Takeda’s 

R&D expertise in the field. 




Collaboration 

Albany Molecular 

Research 


2002 Drug discovery AMRI and Takeda have agreed a 1 year 

basic drug discovery program involving 

identification by AMRI of small molecule 

candidates for a range of undisclosed 

disorders. Takeda will provide funding, 

milestone payments and royalties for 

products resulting from the research. 

Santarus 2002 Lifecycle 

development of 

gastrointestinal drugs 

Oxford Centre for 

Diabetes, Endocrinology 

and Metabolism 

Specialized Health 

Products International 

TAP in-licensed rights to manufacture and 

market products in the USA using 

Santarus technology to expand the 

lifecycle of existing products. TAP initially 

paid $8m and may pay up to $100m if 

new drugs are successfully 

commercialized; $10m milestone paid in 

2005. Takeda exercised its right to 

terminate the agreement in January 2006. 

2002 Diabetes treatments A 5 year partnership agreement was 

signed. Takeda has joined the board of the 

center and donated Yen600m to support 

construction of the second phase of its 

research facilities. 

2002 Syringe safety TAP and SHPI agreed a deal to use SHPI’s 

proprietary safety needle device for TAP’s 

pre-filled syringe products. SHPI will 

receive reimbursement for R&D expenses, 

milestone and royalty payments. 

Gene Logic 2002 Genomics database Takeda subscribed to Gene Logic’s 

BioExpress database for use in its 

genomics-based drug target discovery 

programs. Expanded in 2003, giving 

access to complete dataset, allowing 

assessment of full range of human tissues, 

animal, and cell lines. Subscription 

extended in 2005 through 2006; Takeda 

also gained perpetual license to data 

existing. 

Human and Animal Bridge 

(HAB) Discussion Group 

Biomolecular Engineering 

Research Institute 

2001 Database creation Research into a drug interaction database 

using human liver microsomes. 

2001 Biochemistry Research into the application of 

biomolecular functions. 




Collaboration 


BF Research Institute 2001 Dementia Basic research for development of 

medicines for dementia. 

NEDO Project 2001 Compound screening Co-development of a support system to 

screen pharmaceutical compounds. 

Sumitomo 2001 Automated 

workstations 

Array BioPharma 2001 Small molecule drug 

discovery 

The Institute of Physical 

and Chemical Research 

WHO 2001 Antimalarial drug 

discovery 

Research into a high-performance 

automated chemistry workstation for 

optimization of chemical reactions. 

Takeda will pay fees to Array based on the 

number of Array scientists working on the 

research phase of the agreement. Array 

will be entitled to receive milestone 

payments and royalties based on products 

resulting from the collaboration. Other 

terms were not announced in 2004. 

2001 Gene therapy Joint research into the physiological 

function of p51 oncogene, an original form 

of p53, and its application to medical 

treatment. 

Joint research into antimalarial drug 

discovery. 

Gedeon Richter 2001 Novel drug discovery Joint research into discovery of novel drug 

candidate compounds. 

Discovery Partners 

International 

Vical/Human Genome 

Sciences 

2001 Drug discovery 

research 

collaboration 

2001 Drug design 

technology 

Discovery Partners International 

announced the expansion of an existing 

agreement with Takeda to include 

significant drug discovery research 

collaboration. 

Licensing agreement between Vical and 

Human Genome Sciences, which uses 

Vical’s naked DNA technology and HGS’ 

proprietary genomics database. Vical will 

receive exclusive rights to three genes 

from HGS’ gene discovery program, in 

return for the use of Vical’s technology to 

deliver 3 different gene therapy products. 

Celera Genomics 2000 Genomic database A five-year agreement that will provide 

Takeda with subscriptions to Celera’s 

genome databases and products, including 

the Human Genome Database. 




Collaboration 

Fujisawa 2000 Impotence, obesity 

and baldness 

IPF Pharmaceuticals 

GmbH 


Collaboration for the development of 

products for male impotence, obesity and 

baldness, as well as other conditions 

common in aging men. It was the first 

deal of its kind between two Japanese 

companies. Takeda will begin clinical trials 

of the compounds through TAP in the US. 

Fujisawa will then use the clinical data for 

approval in Japan. 

2000 Peptidomics Long-term research collaboration with TAP 

for research into natural human peptides, 

for the identification of new drug targets 

and candidates. 

Various 2000 SNPs 43 Japanese and international companies 

formed the Pharma SNP Consortium, for 

the research of SNP data relevant to the 

Japanese population. Being coordinated by 

the Japan Pharma Manufacturers’ Assoc., 

it will have Yen1 billion of funding over 

three years. The group will examine SNPs 

from 1,000 Japanese to build a database 

to help in developing drugs tailored for the 

domestic population. 

Pharmacopeia/MSI 2000 Crystal structure Takeda joined MSI’s Pharmaceutical 

Development Consortium, for the creation 

of new computational methods to examine 

crystal structures and predict properties of 

drugs. 

Taisho 2000 International R&D 

collaboration 

Takeda agreed to run international clinical 

trials of Taisho’s drugs. Takeda will have 

priority to negotiate exclusive marketing 

rights to target drug candidates. Target 

territories are North America and Europe. 

Affymetrix 1999 GeneChip Affymetrix granted Takeda access to its 

GeneChip technology. 




Collaboration 

Takeda, Hitachi Ltd. and 

Juntendo University 

Faculty of Medicine 


1999 SNPs A collaboration into the identification of 

SNPs. The project is being run under the 

auspices of the Japan Biotechnology 

Industry Consortium. Lasting for 1 year, 

the project will focus on allergic diseases. 

Takeda will use the information in its drug 

discovery efforts. Hitachi will build a 

large-scale, rapid SNP identification 

system. Some 200 patients with atopic 

dermatitis, and 100 healthy controls, will 

be used to identify at least 10 groups of 

cytokines and cytokine receptor genes. 

Novo Nordisk 1996 Diabetes Research deal for the development of 

compounds for diabetes. The goal is to 

identify orally active drugs for controlling 

blood glucose in Type 2 diabetes. NN will 

contribute its expertise relating to 

receptors for blood glucose regulation. 

Takeda will provide a library of small 

molecules with affinity for these receptors. 

Human Genome Sciences, 

Glaxo SmithKline 

1995 Genome data, 

combinatorial 

chemistry 


Takeda gained access to HGS’ human 

genome database and SB’s combinatorial 

chemistry technology. In 2002 Takeda 

exercised its option to develop and 

commercialize mapatumumab in Japan; 

an option fee has been paid and Takeda 

will also pay milestones and royalties if the 

compounds are marketed in Japan


� Mergers & Acquisitions 

• Year: 2008 

Major Events 

May: Takeda com pleted its Yen1 tril lion ($8.8 bil lion) ac qui si tion (through a cash trans ac tion of $25 per 

share) of Mil len nium Pharmaceuticals, an nounced the pre vi ous month, with Mil len nium be com ing a 

wholly-owned sub sid iary of Takeda but con tin u ing op er a tions as a stand alone busi ness in the US. Pres i - 

dent Dr Deborah Dunsire will con tinue to lead the com pany and Takeda has ex pressed de sires to re tain 

Mil len nium em ploy ees (around 1,000 em ploy ees). This is the larg est ac qui si tion ever made by Takeda 

and more over, any Jap a nese phar ma ceu ti cal com pany, dem on strat ing Takeda’s com mit ment to be come 

a true global phar ma ceu ti cal com pany with grow ing strength in on col ogy, in which Mil len nium has a 

strong pres ence. With sales of $0.5 bil lion in 2007 and net prof its of $15 mil lion, Mil len nium co mes with a 

pipe line con sist ing mainly of on col ogy and in flam ma tory drugs, in clud ing one for in flam ma tory bowel dis - 

ease. Mil len nium’s main stay prod uct is an anticancer proteasome in hib i tor, Velcade (bortezomib), mar - 

keted world wide and in Ja pan by Janssen (part of John son & John son). Velcade posted world wide sales of 

Yen80 bil lion in 2007 and 2008 sales are ex pected to in crease to Yen32-34.5 bil lion in 2008 in the US 

alone; cur rently used as sec ond and third line ther apy in mul ti ple myeloma, it is ex pected to be ap proved 

for first line ther apy in the US in June 2008. Takeda hopes that this prod uct may even tu ally be come a 

block buster with US sales of over Yen100 bil lion, bridg ing the loom ing gap from up com ing pat ent ex pi ries 

of its main stay prod ucts with Prevacid (lansoprazole) set to go ge neric in the next few years and po ten - 

tially switch to OTC in 2009 un der a li cens ing agree ment with Novartis, while pat ent pro tec tion ex pires for 

Actos (pioglitazone) in 2011. An a lysts con sid ered the bid price for Mil len nium as sur pris ingly high, but 

was likely to ward off competition from other potential counter bidders such as Johnson & Johnson, 

thought to be a natural contended due to its co-promotion of Velcade. 

March: Af ter over 30 years as part ners, Takeda and Abbott de cided to dis solve its TAP 50-50 jv with 

Abbott in July, di vid ing it evenly be tween the two com pa nies and then merg ing it with Takeda to be come 

a wholly owned sub sid iary of Takeda Amer ica Hold ings, Inc. The 50% stake in TAP is val ued at 

Yen300-500 bil lion and over all the split seems to be am i ca ble and ben e fi cial to both com pa nies.. Abbott 

will ob tain rights to Lupron De pot along with as sets pri mar ily re lated to this prod uct, and all em ploy ees as 

well as pay ments based on TAP’s other cur rent and cer tain fu ture prod ucts. The new TAP sub sid iary of 

TAH will re tain the other mar keted TAP prod uct, Prevacid (al though Abbott will re ceive around $1.5 bil lion 

from prod uct sales over five years) in ad di tion to cer tain pipe line prod ucts: dexlansoprazole (TAK 

390MR), a pro ton pump in hib i tor await ing ap proval; an other pro ton pump inhibior, ilaprazole (IY 81149) 

and a drug for the treat ment of hyperuricemia in pa tients with gout (TMX 67). The two mar keted TAP 

prod ucts, Lupron and Prevacid, re garded as global stra te gic prod ucts, posted world wide sales of Yen185 

and Yen400 bil lion re spec tively in fis cal 2006. TAP con trib uted around one-third of Takeda’s to tal sales in 

fis cal 2006 and the dis so lu tion and merger of TAP into Takeda will boost the over seas sales ra tio which 

stood at around 50% in 2006. The trans ac tion is said to have no impact on fiscal 2007 results and 

analysts viewed the move as positive for Takeda. 

• Year: 2007 

April: The buyout of Takeda’s in ter est in Wyeth KK (Jap a nese unit of Wyeth) was com pleted by Wyeth af - 

ter four years. The com pa nies re ported that this will have no ef fect on their re la tion ship which re mains 

strong with their cur rent co-pro mo tion of Enbrel. 



March: Takeda is to ac quire Par a digm Ther a peu tics (Sin ga pore) build ing on a CNS al li ance started in 

2005. Par a digm fo cuses on iden ti fy ing small mol e cule tar gets within key gene fam i lies and its pipe line in - 

cludes tar gets and late stage pre clin i cal pro jects in pain, CNS, hor mone de pend ent dis eases such as pros - 

tate and breast can cer as well as met a bolic dis ease. Fi nan cial terms were not dis closed. Par a digm will 

be come a sub sid iary of Takeda Eu rope Hold ings B.V. a wholly owned sub sid iary of Takeda and Par a digm 

will be re named Takeda Cam bridge Lim ited with the sub sid iary in Sin ga pore re named Takeda Sin ga pore 

Pte Lim ited. Par a digm was es tab lished in 1999 by Uni ver sity of Cam bridge (UK) re search ers. This al li ance 

will build on and re place the 2005 CNS agree ment and Paradigms technology and researchers will be 

integrated into Takeda. 

• Year: 2006 

Takeda an nounced to day that all of Takeda’s shares of Mitsui Takeda Chem i cals Inc. (MTCI) had been 

trans ferred to Mitsui Chem i cals, Inc. (Ja pan). Upon trans fer of shares, MTCI changed its name to Mitsui 

Chem i cals Polyurethanes, Inc. MTCI was es tab lished as a joint ven ture be tween MCI (51%) and Takeda 

(49%) in April 2001, and it was stip u lated in the orig i nal agree ment that the trans fer of shares held by 

Takeda would take place af ter five years from the start of MTCI’s com mer cial operation. 

Takeda an nounced plans to sell its do mes tic food prod ucts busi ness to the Jap a nese firm House Foods in 

a fur ther move to fo cus on pre scrip tion drugs. Takeda will ini tially trans fer the op er a tions to a new 

34%-owned tem po rary jv with House, sched uled to be gin in April 2006, sub ject to antimonopoly clear - 

ance, and will in volve the trans fer of most (298) Takeda Food em ploy ees for 18 months be fore the jv is 

dis solved and House ac quires Takeda’s hold ing and con verts to a wholly owned sub sid iary. This jv time is 

con sid er ably shorter than the non-pharma jvs that Takeda nor mally sets up to dis solve af ter five years. 

The ac qui si tion price was not dis closed but given that House Foods is pay ing Takeda Yen19.8 bil lion for 

the 66% stake, the re main ing 34% stake is ex pected to have a price tag of around Yen10 bil lion and in - 

dus try an a lysts think that one time gains are likely to materialize. 

Takeda sold its re main ing 34% share in the BASF Takeda Vi ta min jv in Ja pan to BASF Ja pan, com plet ing 

its exit from the do mes tic bulk vi ta min busi ness. The two com pa nies com bined their Jap a nese bulk vi ta - 

min op er a tions upon the jv es tab lish ment in Jan u ary 2001, un der an agree ment in which Takeda was to 

exit after five years. 

• Year: 2005 

Takeda di vested to Schering-Plough (USA) its 40% stake in the two com pa nies’ Jap a nese an i mal health 

jv, Takeda Schering-Plough An i mal Health, which be came a wholly-owned sub sid iary of S-P, drop ping 

Takeda from its name. This forms part of Takeda’s stra te gic fo cus on pre scrip tion pharmaceuticals, which 

has seen it di vest a num ber of non-core op er a tions over the past few years. 

Takeda bought pri vate US biotech com pany Syrrx in a bid to en hance its R&D op er a tions in the US and its 

pipe line; Takeda is ac tively do ing all it can to achieve this in prep a ra tion for pat ent ex pi ra tions in its older 

drugs. The deal was es ti mated at $270 million. 

• Year: 2002 

Takeda and Gruenenthal (Ger many) reached an agree ment on the trans fer of 50% of the shares in 

Takeda Pharma (Ger many) from Gruenenthal to Takeda. Takeda Pharma was a 50-50 joint ven ture be - 

tween Gruenenthal and Takeda and has sub sid iar ies in Aus tria and Swit zer land. Takeda Pharma will be - 

come a 100% sub sid iary of Takeda Europe. 



• Year: 2001 

Kirin and Takeda es tab lished Takeda-Kirin Foods, a joint ven ture com pany in the food busi ness, in ac cor - 

dance with a ba sic agree ment con cluded in 2000. Kirin has an ini tial 51% stake in the com pany, with 

Takeda own ing 49%. Kirin will even tu ally ac quire all of the shares by 2007. 

Takeda Amer ica, merged its US sub sid iar ies fol low ing bulk vi ta min busi ness re struc tur ing. The com pany 

an nounced the merger of its wholly owned busi ness, Takeda Fi nance USA, with Takeda Amer i can Hold - 

ings in July. The new com pany is called Takeda American Holdings. 

Takeda agreed to hand over mar ket ing of syn thetic rub ber la tex to un listed chem i cal maker Nip pon A and 

l. This move is the first step to ward a planned trans fer of Takeda’s en tire rub ber la tex busi ness some time 

in the fu ture, which re flects the drugmaker’s ef forts to spin off non-core operations. 

• Year: 1998 

Takeda ac quired the 5% of Laboratoires Takeda (France) that it did not pre vi ously own, from Hoechst 

Marion Roussel (now part of sanofi-aventis, France). It was es tab lished in 1978 as a joint ven ture and is 

now a wholly owned sub sid iary of Takeda. 

Takeda ac quired 38.46% of the shares of Takeda Italia Farmaceutici SpA, a jv es tab lished with Lederle in 

1982, from Lederle’s par ent com pany Amer i can Home Prod ucts (now Wyeth, USA). Con se quently, 

Takeda owned 76.92% of TIF (90.91% of vot ing shares) and ac quired man age ment control. 

Takeda an nounced that it had agreed to sell 10% of the shares of Lederle (Ja pan) to AHP, which now 

owns Lederle. Its stake was thus re duced to 40% from 50%, and AHP (now Wyeth) owned 60%. In 1998, 

Lederle (Ja pan) and the eth i cal prod ucts busi ness of Wyeth (Ja pan) were com bined into a new busi ness 

named Wyeth Lederle Japan. 

• Year: 1997 

Takeda ac quired the man age ment rights of Grelan (Ire land), a wholly-owned sub sid iary of Grelan 

Pharmaceuticals (Ja pan). Takeda holds a stake in Grelan. The Irish com pany was es tab lished in 1997, 

but proved a fi nan cial drain on Grelan as it had not be gun op er a tions. Takeda will re name it Takeda Ire - 

land. It will be Takeda’s first over seas man u fac tur ing base. 

• Year: 1992 

Takeda and Roussel-Uclaf (France) an nounced a deal un der which Takeda would pur chase from 

Roussel-Uclaf 45% of the shares of their jv, Takeda SA (France). Ef fec tive Jan u ary 1993, Takeda owned 

95% and R-U re tained 5%. 

• Year: 1988 

In creased stake in Imre (USA) to 10%. 

� Other Major Events 

• Year: 2009 

Jan u ary: Stefan Ziegler ap pointed as CEO of Takeda Pharmaceuticals Asia Pri vate Lim ited (TPAsia), its’ 

wholly owned sub sid iary in Sin ga pore that was es tab lished in Sep tem ber 2008. 



• Year: 2008 

De cem ber : Takeda be gan con struct ing new re search fa cil i ties in Ja pan, ex pected to com plete be fore the 

end of fis cal 2010 (end ing March 2011). This will serve as the cen tre of Takeda’s global re search net work 

con sol i dat ing the drug dis cov ery ca pa bil i ties cur rently lo cated in the cities of Osaka and Tsukuba. 

Sep tem ber: Takeda Pharmaceuticals Asia Pri vate Lim ited (TPAsia), Takeda’s wholly owned sub sid iary in 

Sin ga pore es tab lished and over sees ac tiv i ties in five Asian coun tries (Tai wan Thai land, In do ne sia, China 

and the Phil ip pines). At the same time Takeda es tab lished Takeda Clin i cal Re search Sin ga pore Pri vate 

Lim ited (TCRS) to serve as its cen ter of clin i cal de vel op ment in the Asia-Oceania region. 

Erich Brunn ap pointed new CEO of Takeda Pharmaceuticals Eu rope (TPEU), over see ing ac tiv i ties in six 

mar ket ing sub sid iar ies in Eu rope (Ger many, France, the UK, It aly, Aus tria, and Swit zer land) fol low ing 

post as pres i dent of GmbH over last six years. 

Takeda along with 12 other phar ma ceu ti cal com pa nies has been sued by the At tor ney Gen eral of Kan sas 

for al leg edly over charg ing the state’s Medicaid pro gram for drugs pro vided to patients. 

July: Takeda is pur su ing a new mu tual agree ment pro ce dure un der US/Ja pan tax agree ments in the hope 

of set tling a pay ment of Yen57.1 bil lion which it was or dered to make by Jap a nese tax au thor i ties in June 

2006. This fol lowed an of fi cial as sess ment of prof its earned in the US over six years un der agree ments 

with the now dis solved jv with Abbott (TAP0 for Prevacid (lansoprazole). 

April: Takeda joins HRP ini tia tive to dis cover biomarkers of high risk atherosclerotic plaque, join ing Merck 

& Co and AstraZeneca. 

Takeda an nounced the in au gu ra tion of its wholly-owned sub sid iary Takeda Bio De vel op ment Cen ter Lim - 

ited (Takeda Bio), formed Amgen K.K. which be came a wholly-owned sub sid iary of Takeda in ac cor dance 

with a share trans fer agree ment be tween Takeda and Amgen in Feb ru ary 2008. Masaomi Miyamoto will 

chair the board of Takeda Bio and Hiroyasu Hakamura will be pres i dent. The com pany has about 140 em - 

ploy ees with un dis closed cap i tal. The Amgen Ja pan ac qui si tion re flects Takeda’s plans to re in force its 

pipe line while Amgen can ac cel er ate the de vel op ment of its prod ucts in Ja pan and the de ci sion to li cense 

its sub sid iary to Takeda came about be cause Takeda showed in ter est in a wide range of prod ucts. Al - 

though the cost of the ac qui si tion has not been dis closed, as part of the li cense agree ment in Feb ru ary, 

Takeda has ac quired rights to de velop and mar ket al most all of Amgen’s pipe line (13 prod ucts), ex clud ing 

Amgen’s main prod ucts which have al ready been li censed to Kirin and Daiichi Sankyo, in ad di tion to 

Amgen’s hu man re sources spe cial iz ing in the de vel op ment of biopharmaceuticals. Takeda will pay up to 

$837 mil lion in upfront and de vel op ment mile stone pay ments. The most ad vanced prod uct is Vectibix 

(panitumumab) for rec tal can cer, for which an NDA is be ing pre pared and as such it is ex pected to con - 

trib ute to the achieve ment of Takeda’s mid-term busi ness plan (end ing fis cal 2010). The only other prod - 

uct at a late stage of de vel op ment is motesanib (AMG 706) for can cer, and said to be one of the main 

driv ers of the deal for Takeda. Other prod ucts li censed in clude a num ber for can cer: AMG 386, AMG 479 

and AMG 655; as well as AMG 108 for rheu ma toid ar thri tis and AMG 317 for asthma. The li censed prod - 

ucts will strengthen Takeda’s pri or ity fields of can cer and uro log i cal diseases (12 projects underway 

including line extensions) as well as CNS and bone joint disease (11 projects underway). 

April: Takeda trans ferred all of its shares of Hitachi Inspharma, a jv owned by Hitachi (66%) and Takeda 

(34%) to Hitachi as the sched uled two years have passed since the 2006 agree ment. 



• Year: 2007 

No vem ber: Takeda has es tab lished a new com pany ‘Takdea San Fran cisco, Inc’ (TSF) for ther a peu tic an - 

ti body re search. This is part of Takeda’s 2006-10 ‘Me dium Term Plan’ to en hance de vel op ment ca pa bil i - 

ties to cre ate new drugs in-house. 

Feb ru ary: QLT (USA) signed an agree ment with TAP Pharmaceuticals set tling the US pat ent lit i ga tion, ini - 

ti ated in 2003 claim ing that Atrix’s (now QLT’s) Eligard prod ucts in fringed a pat ent. QLT is to pay 4112.5 

mil lion and Sanofi-Aventis will pay 445 mil lion to Tap who will re lease claims made in the US lit i ga tion 

against the companies. 

Jan u ary: Takeda has sub mit ted a plan for a new re search fa cil ity to be built in the city of Fujisawa, an ap - 

proval is an tic i pated in April 2007. Takeda is also to in te grate its re search cen ters in Osaka and Tsukuba 

to im prove com mu ni ca tion and co-or di na tion. The new fa cil ity to gether with the San Diego re search cen - 

ter will form the core of Takeda’s global re search ca pa bil ity. Re search pri or i ties at the new cen ter in clude 

can cer, CNS and life style re lated dis eases; op er a tions are ex pected to be gin in fis cal 2010 by which point 

Yen70 bil lion will be in vested and more per son nel will be added to the current 1,000 researchers 

employed. 

Takeda plans to cen tral ize fund man age ment of its Eu ro pean sub sid iar ies through the trans fer of com - 

pany owned shares to Takeda Eu rope Hold ings. The move aims to cen tral ize ad min is tra tion of Takeda’s 

op er at ing fund and en hance its presence in Europe. 

• Year: 2006 

Takeda an nounced that Mr Giacomo Di Nepi was to be the CEO of a newly-cre ated Eu ro pean com pany, 

Takeda Pharmaceuticals Eu rope Ltd (TEPU), es tab lished in Au gust 2006. TEPU is a wholly-owned sub sid - 

iary of Takeda and will lead the over all busi ness ac tiv i ties of Takeda’s six sub sid iar ies in Eu rope (in France, 

the UK, It aly, Ger many, Aus tria and Swit zer land) by pro mot ing pan-Eu ro pean strat e gies for the short-, 

mid-, and long-term and by sup port ing the man age ment of the sub sid iar ies in the re gion. Takeda stated, 

“This ap proach will fur ther en hance and com ple ment our solid busi ness struc tures in Eu rope, to wards the 

fur ther growth of Takeda’s business in the region”. 

TPNA (Takeda Phar ma ceu ti cal’s North Amer ica), Takeda’s wholly owned US mar ket ing sub sid iary has 

com pleted con struc tion of new head quar ters in Il li nois where 800 em ploy ees have re lo cated. Takeda al - 

lo cated Yen70 bil lion to ac quire 9.3 mil lion of its own shares over Oc to ber fol low ing the pur chase of 4.5 

mil lion for Yen33.6 bil lion dur ing Sep tem ber said to im prove in ves tor re turn but is be ing seen as a de fen - 

sive tac tic against pos si ble merger and ac qui si tion ac tiv ity. Takeda’s share ac qui si tion pro gram is said to 

rep re sent sig nif i cant spend ing for a com pany with con sid er ation to its R&D spend of Yen170 billion in 

fiscal 2006. 

Le gal ac tion in sti tuted by Abbott against Takeda (al leg ing that Takeda earned ex ces sive prof its from its 

sup ply of lansoprazole to jointly owned TAP Pharmaceuticals) was dis missed in a US court as, ac cord ing 

to the share hold ers agree ment, these claims must be raised in Japan. 

Takeda is to be come sole mar keter of se lected prod ucts from Aska Pharmaceuticals (formed by merger of 

Teikoku Hor mone and Grelan in Oc to ber 2005) in Ja pan from April 1 2006, fol low ing the dis con tinu a tion 

of a pre vi ous Aska agree ment with Dainippon Sumitomo. Aska has a num ber of pre scrip tion prod ucts in - 

clud ing the H2-blocker Altat (roxatidine) which was launched as a switch-OTC product in 2005. 



• Year: 2005 

Abbott is su ing Takeda, al leg ing that it is over charg ing the TAP jv for lansoprazole, es ti mat ing ex cess 

prof its of around $200-300 mil lion for Takeda an nu ally over a 10-year sup ply agree ment. Abbott also 

claims that Takeda forced TAP into ex tend ing through May 2015, an ex clu sive sup ply agree ment that was 

set to expire in May 2005. 

Wyeth ac quired one-quar ter of Takeda’s 40% stake in the com pa nies’ Jap a nese jv Wyeth KK, as part of 

an eq uity trans fer agree ment trig gered by the re cent ap proval and launch of Enbrel in Ja pan and now has 

70% own er ship and full man age ment con trol of its Jap a nese op er a tion which em ploys around 1,700 peo - 

ple. Fi nan cial de tails were not dis closed but were said to re flect fair mar ket value. In May 2003 Wyeth 

(USA) an nounced its in ten tion to buy out Takeda’s 40% share in its Jap a nese jv, over the com ing years, 

con vert ing the op er a tion into a 100%-owned sub sid iary of Wyeth. Both com pa nies also agreed to co-pro - 

mote Wyeth’s Enbrel for rheu ma toid arthritis as well as two unnamed products. 

Takeda sold five small sub sid iary com pa nies to Osaka Gas Chem i cals, as part of a con tin u ing ef fort to 

con cen trate re sources on its core pre scrip tion pharmaceuticals busi ness. The op er a tions in clude wholly 

owned Ja pan EnviroChemicals, spun off two years ago into an in de pend ent sub sid iary as a pre lude to full 

divestment. 

• Year: 2004 

TAP agreed to pay $150 mil lion to re solve civil law suits about the mar ket ing and pric ing of Lupron, push - 

ing to tal com pany pay outs to more than $1 billion. 

New Orlean’s phy si cian, John LaCorte, filed a whistle blow er suit against TAP, al leg ing that the firm vi o - 

lated its agree ment to of fer Medicaid its best price for Prevacid by charg ing up to 20 times more than it 

charged other cus tom ers. 

TAP an nounced the ap point ment of Alan Mac Ken zie as pres i dent, suc ceed ing H Thomas Watkins. 

Takeda agreed with its main un ion to scrap lim its on fi nan cial re wards for em ployee in ven tions which con - 

trib ute to cor po rate rev e nue. The firm in tro duced a scheme in 1998 which al lowed up to Yen10 mil lion per 

em ployee for a max i mum of five years, based on rel e vant world wide sales. The amount was raised to 

Yen30 mil lion two years ago. This ceil ing was re moved and will now be ap plied ret ro spec tively to prod ucts 

launched since 1994. The changes were made in re sponse to a Jan u ary 2004 revision of Japan’s Patent 

Law. 

Masahiko Fujino, for mer chair man of Takeda Chem i cal In dus tries died aged 72. 

Takeda’s UK R&D sub sid iary, Takeda Eu rope Re search and De vel op ment Cen ter an nounced a 90% re - 

duc tion in staff num bers, from 168 to 16 from Au gust 2004. 

A Wis con sin court sued TAP and 19 other phar ma ceu ti cal com pa nies for pub lish ing false av er age whole - 

sale prices (AWPs), lead ing to higher costs for pay ers. The law suit did not spec ify what dam ages or res ti - 

tu tion Wis con sin is seek ing. How ever, the As so ci ated Press quoted the at tor ney gen eral as say ing “the 

numbers are very large”. 

The US su preme court over turned an ap peals court rul ing which would have al lowed for eign pur chas ers 

of vi ta mins man u fac tured by non-US com pa nies to sue in US courts for vi o la tions of the Sherman an ti - 

trust law, even though all the vi ta mins were bought out side the USA. Takeda Vi ta min & Food USA is one 

of the defendants. 



A Penn syl va nia court is su ing 13 ma jor phar ma ceu ti cal com pa nies, in clud ing TAP, ac cus ing them of in - 

flat ing prices in an al leged scheme that cost the gov ern ment, in sur ers, and con sum ers hun dreds of mil - 

lions of dol lars. If the law suit suc ceeds, con sum ers who pur chased ar ti fi cially over priced drugs would be 

eligible for rebates. 

Takeda busi ness of fice man ag ers will per son ally take on the ed u ca tion/train ing re spon si bil ity. The nearly 

270 team lead ers were as signed ei ther man ag ers of the nearly 70 new of fices or “ex pert MRs” (about 

170) who dem on strate ex em plary de tail ing ac tiv i ties to the other MRs. Takeda plans to hire 240 new MR 

can di dates in the year to March 31 2005. Takeda an nounced the es tab lish ment of Takeda Global Re - 

search and De vel op ment Cen ter (TGRD) in Il li nois, USA. The new or ga ni za tion, to be lo cated on TPNA’s 

cam pus in Lincolshire, Il li nois, will in te grate the clin i cal de vel op ment ac tiv ity of TPNA’s R&D group and 

Takeda’s Eu ro pean R&D cen ter. This will in volve the trans fer of TPNA’s ex ist ing R&D to the new cen ter. 

The Takeda’s Eu rope R&D Cen ter will re port to TGRD. The new or ga ni za tion will be headed by Dr John 

Yates, former VP for Medical and Scientific Affairs at Merck & Co (USA). 

• Year: 2003 

A US Dis trict Court judge ruled that lit i ga tion aris ing from al leged im proper pric ing of Lupron (leuprorelin) 

by Takeda, TAP and Abbott, could pro ceed. The lit i ga tion claims that il le gal mar ket ing and sales prac tices 

re sulted in ex ces sive costs be ing paid by consumers. 

Takeda an nounced a re or ga ni za tion of its do mes tic pro duc tion sys tem, in volv ing clo sure of its plant in 

Fujisawa by March 2006 and re struc tur ing its ac tiv i ties at Hikari. Pro duc tion of con sumer healthcare 

prod ucts will move to Fukuchiyama, and eth i cal man u fac ture will move to Hikari, where Takeda plans to 

in vest Yen15 bil lion. This will be come Takeda’s main pro duc tion fa cil ity and will in clude pro duc tion of spe - 

cific raw ma te ri als, for mu la tion of vac cines and microcapsule for mu la tion of Leuplin (leuprorelin). 

Takeda’s Osaka plant is to con tinue its spe cial ist production and research until further notice. 

Takeda’s wholly owned US hold ing com pany, Takeda Amer i can Hold ings, re ceived a cash in jec tion of 

$2.6 bil lion from the par ent com pany in mid 2003. The hold ing com pany over sees both Takeda 

Pharmaceuticals north Amer ica TPNA and TAP, and the move will help to fund fur ther busi ness ex pan sion 

in the USA. 

Chugai (Ja pan) an nounced plans to sell the Takeda Re search Lab o ra tory site to Kajima (Ja pan). 

Takeda bought back 3% of its stock in an ef fort to bol ster its sag ging share price. The firm will buy up to 

30 mil lion of its own shares (Yen140 bil lion). 

The Aus tra lian Com pe ti tion and Con sumer Com mis sion filed a com plaint against Roche, BASF, and 

Takeda, al leg ing they par tic i pated in fix ing the price of vi ta min C. The com pa nies were part of a vi ta mins 

car tel which ended in 1999 and took part in fix ing global prices of vi ta min C between 1991 and 1995. 

Takeda signed a con sult ing agree ment with BioConsul Drug De vel op ment (USA). BCDD will ad vise on 

tech ni cal and fi nan cial as pects of li cens ing agree ments with US bio tech nol ogy and biopharmaceutical 

companies. 

• Year: 2002 

Sumitomo Chem i cal (Ja pan) and Takeda con cluded a jv and trans fer-of-busi ness agree ment ini ti ated in 

July 2002. The two com pa nies have es tab lished the jv Sumitomo Chem i cal Takeda Agro Com pany, which 

took over Takeda’s do mes tic agro chemi cal busi ness at the be gin ning of No vem ber 2002. Sumitomo will 

con trol 60% of the com pany, and Takeda 40%. Af ter five years, the To kyo-based jv (named Sumika) 

may be in te grated into Sumitomo’s agro chemi cals busi ness. The jv has a cap i tal of Yen9,380 mil lion and 



420 em ploy ees (in clud ing its four 100% sub sid iar ies). The new ven ture is ex pect ing con sol i dated sales of 

around Yen36 bil lion. The ar range ment was ap proved by both Jap a nese reg u la tors and the EC, on the ba - 

sis that Takeda’s busi ness was largely domestic and Sumitomo’s was largely international. 

Takeda an nounced plans to sell its 32.5% hold ing in Shimizu Seiyaku to Suzuyo (Ja pan). Takeda will end 

its sales con tract with Shimizu Seiyaku at the end of March 2003. The moves fol low an agree ment by Aji - 

no mo to to ac quire Shimizu Seiyaku and its wholly-owned sub sid iary Shimizu Med i cal by the end of 2002. 

Takeda was re quired to pay Yen500 mil lion in pen alty taxes fol low ing in cor rect book ing of in come and ex - 

penses dur ing 2000 and 2001. 

A for mer TAP sales rep re sen ta tive pleaded guilty to a charge of vi o lat ing the US pre scrip tion Drug Mar ket - 

ing Act in re spect of Lupron (leuprorelin). The rep re sen ta tive had failed to ob tain a writ ten re quest from a 

phy si cian for free sam ples, and could face a jail sen tence plus a $100,000 fine. By July 2002, 14 TAP em - 

ploy ees in clud ing three se nior ex ec u tives had been charged since the start of the Fed eral in ves ti ga tion 

into Lupron-related fraud. 

TPNA (Takeda Pharmaceuticals North Amer ica) re struc tured its se nior ex ec u tive team and ap pointed a 

new Pres i dent, Mark Booth, to take man age ment re spon si bil ity for all TPNA’s business. 

Con tracts be tween Takeda and Ad vance PCS, a US phar macy ben e fit man age ment com pany, be came 

the sub ject of an in ves ti ga tion by the Phil a del phia US At tor ney’s Of fice in ves ti gat ing whether Ad vance 

PCS prop erly re ported re bates to Fed eral Em ployee Health Ben e fit pro grams. Takeda is one of 14 man u - 

fac tur ers whose contracts are being examined. 

Takeda an nounced it is to sell its syn thetic rub ber la tex busi ness to Nip pon AL, a jv be tween Sumitomo 

Chem i cal (Ja pan) and Mitsui Chem i cals (Ja pan). For mal trans fer was due in October 2002. 

TAP ex plained that it was not the tar get of an in ves ti ga tion that re sulted in sev eral US health ben e fit man - 

age ment com pa nies re ceiv ing re ceived Fed eral sub poe nas in April and May 2002. Some of the com pa nies 

were asked for doc u ments re lat ing to their relationship with TAP. 

TAP’s Phar ma ceu ti cal Eth ics and Com pli ance Of fi cer agreed to chair the US Health Care Com pli ance As so - 

ci a tion task force to de velop mea sure ments to eval u ate the ef fec tive ness of cor po rate com pli ance pro - 

grams. As part of its set tle ment of crim i nal and civil charges re lated to Lupron pro mo tion, TAP agreed to 

an ex ten sive corporate integrity program 

Takeda an nounced plans to in vest around Euro80 mil lion in a new bulk phar ma ceu ti cal pro duc tion plant 

in Clondalkin, Ire land. It will be Takeda’s first such fa cil ity out side Ja pan. Op er a tions are sched uled to be - 

gin in 2004, when the plant will ini tially pro duce Actos (pioglitazone) for Eu ro pean and US mar kets and 

new com pounds for clin i cal tri als. Takeda al ready has a for mu la tion and pack ag ing plant in Ire land. The 

two sites will be run as sep a rate com pa nies, with the new bulk plant tak ing over the Takeda Ire land 

name. The ex ist ing pack ag ing and for mu la tion site will be renamed Takeda Ireland Products. 

• Year: 2001 

The Jap a nese Phar ma ceu ti cal Group (JPG), was set up in the UK to rep re sent the views of 10 R&D Jap a - 

nese com pa nies, in clud ing Takeda, which sell branded med i cines to the NHS. 

Takeda an nounced its in ten tion to es tab lish an in vest ment com pany in the USA, called Takeda Re search 

In vest ment (TRI) on the west coast, which will pro vide fund ing for bio tech nol ogy start-ups and 

early-stage ven tures con duct ing re search or de vel op ing tech nol o gies for in no va tive drug dis cov ery. TRI 

was given an in vest ment fund of $100 mil lion and will take stakes in tar get com pa nies to ac cel er ate 

Takeda’s own re search activities in the area by 2005. 



Takeda was fined Euro37.1 mil lion by the EC Com mis sion over vi ta min price-fix ing be tween 1989 and 

1999. The to tal fine of Euro855.2 mil lion was the larg est ever im posed on com pa nies op er at ing a car tel in 

the EC, which in cluded Roche, BASF, and Daiichi Pharmaceuticals. 

Takeda be gan con struc tion of a new Yen17 bil lion genomics R&D fa cil ity in Tsukuba Ja pan, ded i cated to 

the anal y sis of gene and pro tein func tion and re gen er a tive gene re search, and speed ing up the de vel op - 

ment of genome-based drugs. 

TAP Phar ma ceu ti cal Prod ucts pleaded guilty to a crim i nal charge and agreed to pay the larg est ever crim i - 

nal fine in a health care fraud case, as in ves ti ga tions con tin ued re gard ing pre scrip tion drug scams and the 

il le gal mar ket ing of its anticancer drug Lupron. The com pany agreed to pay $875 mil lion to re solve crim i - 

nal and civil charges that it fraud u lently priced and mar keted the prostate cancer drug. 

Takeda and Nip pon A&L an nounced that they reached a tie-up agree ment re gard ing Takeda’s syn thetic 

rub ber la tex busi ness on July 1. The two com pa nies plan to sign an agree ment which trans fers Takeda’s 

syn thetic rub ber la tex busi ness to Nippon A&L. 

TAP Phar ma ceu ti cal Prod ucts (a jv be tween Abbott and Takeda) signed a co-pro mo tion deal with Sol vay 

(Bel gium) over the Sol vay drug AndroGel (tes tos ter one). Sol vay ini tially ex pected sales of $50 mil lion, 

but raised its fore cast to $100 mil lion af ter its Unimed Pharmaceuticals unit signed the co-pro mo tion deal 

with TAP. 

Takeda Pharmaceuticals North Amer ica, and Lilly an nounced they are un der writ ing and ed u ca tional pro - 

gram called Part ners Against In su lin Re sis tance. The ini tia tive is de signed to pro mote aware ness about 

in su lin re sis tance and its role in Type 2 di a be tes and re lated com pli ca tions, such as cardiovascular 

disease. 

Takeda in vited ap pli ca tions for an early re tire ment pro gram sched uled to start in April 2003. The pro gram 

is open to work ers aged 35 or over and is pri mar ily aimed at of fer ing var i ous op tions to em ploy ees, in - 

clud ing job changes, rather than a re duc tion of la bor ex penses. The com pany has not set a tar get for job 

cuts under the program. 

TAP con firmed that it was be ing in ves ti gated by the Texas state at tor ney over the mar ket ing and pric ing 

of Lupron. TAP is also be ing ex am ined by the US Jus tice De part ment for prac tices such as en cour ag ing 

phy si cians to bill in sur ance com pa nies for free sam ples of Lupron (at $400 to $550 per in jec tion). The in - 

ves ti ga tion be gan in 1998 in Boston and ru mors of a set tle ment spread in early 2001 af ter TAP said it was 

chan nel ing money into a le gal re serve fund. An un em ployed woman from Saitama Pre fec ture was sen - 

tenced to two-and-a-half years in jail af ter threat en ing to con tam i nate Takeda’s eye wash prod ucts. Her 

ac tions were said to have caused Takeda Yen150 mil lion in losses af ter it was forced to re call its Mytear 

SG and Catalin K prod ucts. Ms Fujino also black mailed another Japanese pharmaceutical company, 

Santen. 

Takeda said it planned to outsource 50% of its phar ma ceu ti cal out put by 2003 (cur rently 30%). The tar - 

get will be achieved through the con sol i da tion of pro duc tion of hos pi tal drugs and the clo sure of a plant in 

Kanagawa Pre fec ture re spon si ble for man u fac tur ing in ject able drugs. It was orig i nally meant to close in 

2005, but this has now been brought for ward to De cem ber 2003. Takeda’s pro duc tion will be shifted to 

other com pa nies, both do mes tic and in ter na tional. The com pany said it was tak ing the step due to slow 

growth in the do mes tic mar ket and grow ing com pe ti tion from abroad. Hos pi tal drug man u fac ture will be 

cen tered on Takeda’s plants in Osaka and Yamaguchi. Its num ber of em ploy ees in volved in pro duc tion 

will fall to 700 in 2005, from 1,200, already 25% down from 1998. 

Takeda Amer ica sold its en tire stake in Takeda Vi ta min & Food USA to BASF. The price was not dis closed. 

The sale fol lowed the July 2000 agree ment be tween the two com pa nies to merge their bulk vi ta min op er - 

a tions. 



• Year: 2000 

Takeda cre ated a sec tion on its web site for the sub mis sion of li cens ing pro pos als from for eign bio tech nol - 

ogy firms and re search sci en tists lack ing the re sources to de velop their own prod ucts or tech nol o gies. 

Takeda will form re search al li ances and/or mar ket ing part ner ships for those sug ges tions deemed ap pro - 

pri ate. It be came the first Jap a nese phar ma ceu ti cal firms to seek such partnerships through the Internet. 

Six bulk vi ta min man u fac tur ers in clud ing Takeda set tled US le gal ac tions aris ing out of global price-fix ing 

in the vi ta min mar ket, for up to $325 mil lion. Takeda will pay a max i mum of $27.3 mil lion, to be re corded 

as a spe cial charge against its mid-year earn ings re sults for the year to March 31 2001. Daiichi, Eisai, 

Aventis, BASF and Roche were the other com pa nies in volved in the set tle ment. The EU is also in ves ti gat - 

ing a car tel, and ap proached 13 companies in July 2000. 

Takeda and Mitsui Chem i cals (Ja pan) agreed to es tab lish a joint ven ture (Mitsui Takeda Chem i cals) in Ja - 

pan that will merge the com pa nies’ ure thane and com pos ite ma te ri als busi nesses. This will en able 

Takeda to di vest this busi ness as a move to wards fo cus ing on its core phar ma ceu ti cal area. Sub ject to 

reg u la tory ap proval, the new busi ness was sched uled to be gin op er a tions in 2001. Af ter five years, Mitsui 

will acquire Takeda’s 49% share. 

Lilly and Takeda an nounced an un re stricted ed u ca tional grant to the US Na tional Di a be tes Ed u ca tion Ini - 

tia tive. The funds will be used for the de vel op ment of pro grams for the man age ment of Type 2 diabetes. 

A group of 43 Jap a nese phar ma ceu ti cal firms, in clud ing Takeda, formed a group to con duct re search on 

sin gle nu cle o tide polymorphisms. 

Takeda and BASF an nounced plans to com bine their bulk vi ta mins busi nesses. The com bined op er a tion 

will have ap prox i mately 30% of the global vi ta mins mar ket. In Ja pan, a jv will be cre ated, owned 34% by 

Takeda. Takeda’s vi ta min sub sid iar ies in the US, Can ada, Ger many and Sin ga pore will be trans ferred to 

BASF. Out side Ja pan, BASF will as sume sole re spon si bil ity for the world wide mar ket ing of the com bined 

vi ta min prod uct range. Takeda’s man u fac tur ing tech nol ogy and pat ents will be trans ferred to BASF, but 

Takeda’s Vi ta mins and Food Com pany will con tinue to pro duce bulk vitamins, for exclusive supply to 

BASF. 

Takeda an nounced plans to ter mi nate its poly ure thane jv agree ment with BASF. Takeda’s 50% share of 

Takeda Badisches Ure thanes In dus tries (TBU) was trans ferred to BASF Ja pan. Takeda ex plained that the 

busi ness per for mance of TBU had been dis ap point ing, so it de cided to dis con tinue its investment. 

Takeda’s new pro duc tion fa cil ity in Ire land went on line. The com pany spent Yen4 bil lion on the fa cil ity, 

which has an out put ca pac ity of 750,000 tons per an num, and pro duces lansoprazole, mostly for the US 

mar ket. The plant will also produce Actos. 

Takeda an nounced the merger of its wholly owned US sub sid iar ies, Takeda Pharmaceuticals Amer ica 

(TPA) and Takeda Amer ica Re search & De vel op ment. The lat ter’s func tions were trans ferred to TPA, for - 

merly only re spon si ble for sales and mar ket ing, as of De cem ber 31 2000. Takeda hoped the strength - 

ened link be tween its US mar ket ing and R&D op er a tions would max i mize the potential of every product. 

The Bar ce lona Pro vin cial Court ruled that Boral Quimica SA (Spain) must re frain from man u fac tur ing or 

mar ket ing lansoprazole, due to in fringe ment of Takeda’s Span ish pat ent. The rul ing set tled a case be gun 

by Takeda in 1994; it re ceived a pos i tive ver dict in 1997, but Boral ap pealed. This ap peal has now been 

dismissed. 

TAP Hold ings changed its name to TAP Phar ma ceu ti cal Prod ucts. 



The Fed eral Court of Can ada im posed a C$5.2 mil lion fine on Takeda for con spir a cies to fix prices and al lo - 

cate mar ket share for two vi ta min prod ucts. The Ca na dian Com pe ti tion Bu reau said Takeda had pleaded 

guilty to par tic i pat ing in in ter na tional con spir a cies be tween 1991 and 1995, in volv ing vi ta mins B2 and C. 

In ad di tion to the fine, the court im posed a ban on the com pany to pre vent it re peat ing com pe ti tion of - 

fenses in Can ada for a pe riod of ten years. Takeda stated that it would post a spe cial loss of Yen400 mil - 

lion for the year ending March 31 2000 to cover the fine. 

Formed a jv with Schering-Plough’s (USA) Jap a nese sub sid iary, Schering-Plough KK, for an i mal health. 

Takeda will trans fer the an i mal health busi ness of its ‘Agro Com pany’ to the new busi ness, which will be 

known as Takeda Schering-Plough An i mal Health KK. Takeda be lieved the move would strengthen its ac - 

tiv i ties in this area. 

It was an nounced that Takeda planned to team up with lo cal firms in other Asian na tions to man u fac ture 

and mar ket OTC drugs. It al ready had an agree ment for the gas tro in tes ti nal prod uct Shin Biofermin-S 

tab lets in South Ko rea with Dong-A (South Ko rea). By the end of 2000, it planned to sign an agree ment 

with a Tianjin-based com pany that will man u fac ture and mar ket its OTC prod ucts in China. Takeda hoped 

to grad u ally ex pand such tie-ups with lo cal com pa nies to other Asian nations. 

Takeda com pleted the con struc tion of a new pi lot-scale pro duc tion plant on the site of its main fac tory in 

Osaka. The fa cil ity will man u fac ture small quan ti ties of com pounds for use in clin i cal tri als and pro duc tion 

scale-up stud ies. The com pany is fac ing in creas ing de mand for trial quan ti ties of its com pounds as it in - 

creases its in ter na tional development activities. 

Takeda and Taisho (Ja pan) agreed to col lab o rate on the de vel op ment of Taisho’s drugs for in ter na tional 

markets. 

• Year: 1999 

Takeda filed law suits against OWL Pharmaceuticals and Oakwood Lab o ra to ries with a US dis trict court 

claim ing in fringe ment of 12 pat ents re lated to its leuprorelin de pot for mu la tion. OWL had sub mit ted an 

ANDA in the US for a ge neric ver sion of Lupron De pot. The suit called for a halt to ac tiv i ties that in fringe 

Takeda’s pat ents and post pone ment of FDA ap proval un til the pat ents ex pire, which ac cord ing to Takeda 

will not be until after 2010. 

Six phar ma ceu ti cal com pa nies, in clud ing Takeda, agreed a $1.7 bil lion set tle ment with at tor neys rep re - 

sent ing US buy ers of bulk vi ta mins, which had filed a class ac tion law suit al leg ing price-fix ing. Takeda’s li - 

a bil ity is in the region of $100 million. 

Takeda was named as one of 12 Jap a nese com pa nies in a ven ture with the World Health Or ga ni za tion to 

de velop antimalaria drugs. These will be phased in within the next ten years to re place ex ist ing treat - 

ments, which are not ef fec tive against new strains of the disease. 

Takeda an nounced plans to cut the num ber of its do mes tic pro duc tion work ers in half, to 700, by March 

2006. Dur ing 2000, the to tal num ber of Takeda em ploy ees was ex pected to fall from 9,100 to 8,500, with 

nor mal re tire ments ac count ing for 300 re duc tions by the end of March 2000. 

Takeda an nounced that to sell its wholly-owned feed ad di tive sub sid iary, Takeda Kagaku Shiryo Co, to 

BASF Ja pan. BASF and Takeda have co op er ated in the ad di tive area since 1997. 

Takeda re vealed that it was fac ing a civil law suit in the US with re gard to its in volve ment in an in ter na - 

tional car tel that fixed global vi ta min prices. BASF (Ger many) and Roche (Swit zer land) were fined by the 

US gov ern ment for their in volve ment. Rhone-Poulenc (now Aventis, France) was ex cused for co op er at - 

ing with in qui ries. All the com pa nies faced pri vate suits. Eisai (Ja pan) was also likely to be named as a 

defendant. 



Takeda an nounced that it was in te grat ing its two wholly-owned agro chemi cal sub sid iar ies, Tohoku 

Takeda Kasei Chem i cals and Takeda Agro. As of April 1, they formed the new com pany Takeda Agro Man - 

u fac tur ing. 

• Year: 1998 

Takeda an nounced plans to ex pand its clin i cal test ing op er a tions in the US. It al ready has two R&D bases 

in the coun try through its joint ven ture with Abbott (USA), TAP, and Takeda Amer ica R&D Cen ter, a 

wholly-owned subsidiary. 

Takeda Eu rope Hold ings, a wholly owned sub sid iary of Takeda, es tab lished its own de vel op ment unit, 

Takeda Eu rope R&D Cen ter, in Lon don. Takeda planned to close its R&D cen ter in Frank furt, Ger many. 

The new en tity will be re spon si ble for over see ing Eu ro pean de vel op ment of Takeda’s new drugs and im - 

prov ing the ef fi ciency of the R&D process. 

Takeda Pharma GmbH (Ger many), the 50:50 jv with Gruenenthal (Ger many), es tab lished a 

wholly-owned sub sid iary, Takeda Pharma AG (Swit zer land). 

Takeda an nounced plans to es tab lish an in de pend ent, wholly owned phar ma ceu ti cal mar ket ing com pany 

in the US, Takeda Pharmaceuticals Amer ica. It will be cap i tal ized at $100 mil lion, and mar ket Actos 

(pioglitazone) in con junc tion with Lilly (USA), as well as co-pro mote se lected Lilly insulin products. 

Takeda an nounced a pro posal to change com pany rules to al low it to buy back up to 80 mil lion of its is - 

sued shares. 

The Jap a nese au thor i ties told Takeda to halt man u fac tur ing and sale of Avan (idebenone), a ce re bral me - 

tab o lism improver. A num ber of sim i lar prod ucts from other man u fac tur ers were also delisted. Orig i nally 

ap proved in the 1980s for the im prove ment of brain me tab o lism in pa tients who had suf fered a stroke or 

hem or rhage, they were later ap proved for use in con di tions such as se nile de men tia. Re-eval u a tion of 

these drugs showed them to be in ef fec tive. An a lysts noted that sales of these prod ucts had been fall ing 

and that the withdrawal would simply accelerate the process. 

Takeda Italia ac quired a man u fac tur ing plant in Cerano, It aly from Societa Prodotti Antibiotici (SPA). 

Takeda es tab lished Takeda Eu rope Hold ings in Lon don. This fol lowed the 1997 es tab lish ment of Takeda 

Amer ica Hold ings in the US. The es tab lish ment of these two com pa nies was aimed at help ing Takeda ac - 

cel er ate its in de pend ent busi ness de vel op ment over seas. The new com pany (which has cap i tal of 

STG60.7 mil lion) was es tab lished by in vest ing shares of Takeda’s five ex ist ing Eu ro pean subsidiaries and 

jv companies in kind. 

Takeda an nounced that its food and vi ta min di vi sion had merged with the bulk vi ta min pro duc tion sub - 

sid iary Takeda Chem i cal Prod ucts USA and the mar ket ing sub sid iary Takeda USA to cre ate Takeda Vi ta - 

min & Food USA. 

• Year: 1997 

The US De part ment of Jus tice be gan a probe of TAP’s mar ket ing of Lupron, for pros tate can cer. Takeda 

es tab lished Takeda Amer ica Hold ings, cap i tal ized at $118 mil lion, which will man age all the US ac tiv i ties 

of Takeda. TAP has es tab lished Takeda in the US to some ex tent, but not hav ing a ma jor ity share has ap - 

par ently made draw ing up mar ket ing strat e gies dif fi cult. Takeda was also re ported to be plan ning a move 

to quar terly set tle ment of ac counts and seek ing a list ing on the NYSE. Shoji Isahaya, Pres i dent of Takeda 

Amer ica, be came Pres i dent of TAH. The com pany was cap i tal ized through stock trans ferred from TAP 

Holdings and Takeda America R&D Center. 



Takeda an nounced it was con sid er ing mov ing pro duc tion of five an ti bi ot ics (lilacillin, melysin, amolin, 

solcillin and vasicillin) to Meiji Seika’s In do ne sian sub sid iary, Meiji In do ne sian Phar ma ceu ti cal In dus tries, 

due to the in tro duc tion of stricter GMP reg u la tions in Ja pan. These re quire sep a rate man u fac tur ing of 

peni cil lins and cephalosporins. Takeda ap plied to im port the an ti bi ot ics into Ja pan. The move was also 

part of Takeda’s re struc tur ing plan to improve costs and production. 

Takeda set up Takeda UK to man age sales, in clud ing those of Amias (candesartan cilexetil), and Basen 

(voglibose), and launch new prod ucts in de pend ently. 

• Year: 1996 

Takeda an nounced the com ple tion of a “Bio-Re search Build ing” at its Osaka plant. The Drug Safety Re - 

search Lab o ra to ries in Takatsuki City will move into the new re search fa cil ity to strengthen ties with the 

com pany’s Phar ma ceu ti cal Re search Di vi sion and in crease the ef fi ciency of R&D operations. 

Takeda an nounced plans for a new man u fac tur ing fa cil ity at its Hikari site in Yamaguchi Pre fec ture to 

man u fac ture a de pot for mu la tion of leuprorelin, and an in ject able form of lansoprazole. 

Tianjin Pharmaceuticals Takeda Co, Takeda’s joint ven ture with Lisheng Phar ma ceu ti cal Fac tory Tianjin 

(China), be gan op er a tions. 75%-owned by Takeda, it will man u fac ture Takeda drugs and carry out sales 

pro mo tion and mar ket ing ac tiv i ties, with med i cal rep re sen ta tives op er at ing from sales of fices in Beijing, 

Tianjin, Shanghai and Guangzhou. 

• Year: 1995 

Takeda Pharma GmbH (Ger many), a joint ven ture with Gruenenthal, es tab lished Takeda Pharma 

GesmbH (Aus tria). 

Takeda opened a new UK cen ter in Lon don. This was re spon si ble for con duct ing clin i cal tri als in the UK 

and Ire land un der as sign ment from, and jointly with, the R&D Cen ter in Frank furt, Germany. 

Takeda an nounced a cut in the work force of 32% as part of a re struc tur ing plan. The staff cuts will take 

place grad u ally with staff num bers be ing re duced by about 3,500 to ap prox i mately 7,500 by 2005. 

• Year: 1994 

Takeda and Astra (now AstraZeneca, UK) reached an out-of-court set tle ment of all le gal ac tions re lat ing 

to their pat ent dis pute con cern ing omeprazole and lansoprazole. Astra had al leged that Takeda’s 

Takepron in fringed its pat ent for Losec. The two also an nounced plans to co-de velop Takeda’s Blopress 

(candesartan cilexetil). 

• Year: 1993 

Takeda im ple mented a ma jor re or ga ni za tion of its three US sub sid iar ies. Takeda Chem i cal Prod ucts 

(TCP) merged with Takeda USA and Takeda Fi nance to form Takeda America. 

Takeda an nounced its with drawal from the food busi ness in Thai land when it sold its share in the joint 

ven ture Better Home Foods. 

• Year: 1992 

Takeda set up a sales sub sid iary in Sin ga pore, Takeda Vi ta min and Food Asia Pte. 



• Year: 1990 

Takeda es tab lished a wholly owned sub sid iary, Takeda Chemtech based within the pre mises of the 

Tokuyama Plant, it pro duces bulk drugs and in ter me di ates. TAP Pharmaceuticals amal gam ated the 

Takeda-Abbott R&D Part ner ship, mak ing TAP a phar ma ceu ti cal en ter prise with R&D and mar ket ing ca pa - 

bil i ties. Its HQ was re lo cated from North Chi cago to Deerfield, Illinois. 

Takeda an nounced sev eral or ga ni za tional changes in clud ing the es tab lish ment of a vi ta min and food di vi - 

sion (from the for mer fine chem i cal and food di vi sions) and the for ma tion of a healthcare di vi sion (OTC 

prod ucts and cosmetics). 

• Year: 1980s 

Sales of the antiulcerant Maon (spizofurone) were sus pended due to liver tox ic ity. 

Opened a new R&D cen ter in Frank furt, to sup port sub sid iar ies and act as a li ai son point for the Eu ro pean 

joint ven tures with Gruenenthal, Amer i can Cy an a mid for It aly, and Roussel-Uclaf for France. 

A Takeda-Abbott R&D part ner ship was es tab lished. All new prod ucts ap proved in the US were to be 

trans ferred to the TAP joint ven ture for mar ket ing. 

Takeda ex panded its Ital ian jv and re named it Takeda Italia Farmaceutici. It also ob tained a li cense per - 

mit ting the lo cal man u fac ture of drugs, for merly done by Cy an a mid Italia. 

Takeda agreed to form an Ital ian joint ven ture with Cy an a mid Italia. 

TAP Pharmaceuticals, a US joint ven ture with Abbott Lab o ra to ries (USA), com menced op er a tions. 

Es tab lished Takeda Chem i cal Prod ucts USA in North Carolina. 

Set up Takeda Pharma GmbH in Ger many, a 50:50 joint ven ture with Gruenenthal (Ger many). 

• Year: 1970s 

Laboratoires Cassenne-Takeda (now Laboratoires Takeda) was set up as a joint ven ture in France with 

Roussel-Uclaf (France). 

Takeda agreed to es tab lish TAP Pharmaceuticals, a joint ven ture with Abbott. 

Takeda es tab lished Davao Cen tral Chem i cal (Phil ip pines). 

Takeda es tab lished Cen tury Chem i cal Works Sdn Bhd (Ma lay sia) and PT Takeda In do ne sia. 

• Year: 1960s 

Takeda set up Takeda (Thai land). 

Takeda es tab lished Boie-Takeda Chem i cals (Phil ip pines). 

Takeda USA was es tab lished. 

Es tab lished Takeda Chem i cal In dus tries (Tai wan) and Takeda Im port-Ex port (Ger many). 

Takeda es tab lished Laboratorios Takeda de Mex ico, SA de CV (Mex ico). 



Takeda and Amer i can Cy an a mid (USA) set up a 50:50 joint ven ture, Lederle Ja pan. 

• Year: 1877 

The Takeda com pany was es tab lished in Osaka, Ja pan. 

• Year: 1781 

Chobei Takeda I es tab lished a whole sale drug busi ness. 


IMS COM PANY PRO FILES TAKEDA SUBSIDIARY LISTING 

Takeda Subsidiary Listing 

The fol low ing is a list of the main phar ma ceu ti cal sub sid iar ies and rep re sen ta tive of fices of the Takeda 

group. The in for ma tion is taken from the IMSWorld pub li ca tion IMS Com pany Search. Sub sid iary de - 

tails are ob tained us ing a va ri ety of in for ma tion sources, in clud ing send ing ques tion naires di rectly to the 

com pany in each coun try, as well as in for ma tion pro vided by the com pa nies which are pro filed. The prod - 

uct, ther a peu tic range and sales in for ma tion is taken from the IMS MI DAS database. 

� AUSTRIA 

TAKEDA PHARMA 

Full Name: Takeda Pharma Ges.m.b.H. 

Street Ad dress: Seidengasse 33-35, A-1070 

Wien 

Tel: +43 1 524 40 64 

Fax: +43 1 524 40 66 

Home Page: www.takeda.at 

De scrip tion: Sales/detailer. Prod uct ranges in - 

clude: phar ma ceu ti cal prod ucts (pre scrip tion). 

Es tab lished 1993. 72 phar ma ceu ti cal em ploy ees 

in 2007. 

Rep re sen ta tives/De tail ers (Pharm, Num - 

ber): 21-50 (2007) 

Con tacts (Pharm): Chair man: Dr Helmut 

Hasibeder 

Sub sid iary of: Takeda Pharma, Ger many 

(100%) 

Phar ma ceu ti cal Sales: US$ 60-65 mil lion 

Prod ucts (% of Sales by Lead ing 5): 

95-100% 

Ther a peu tic Classes (% of Sales by Lead ing 

5): 95-100% 

Dose Forms (% of Sales by Lead ing 5): n.a. 

Prin ci pal Prod ucts: 

BLOPRESS PLUS (an gio ten sin-II an tag o nist com - 

bi na tion) 

TRENANTONE (cytostatic hor mone) 

BLOPRESS (an gio ten sin-II an tag o nist plain) 

ACTOS (antidiabetic oral) 

AGOPTON (antiulcerant) 

Ther a peu tic Range: 

renin-an gio ten sin sys tem agents 47% 

cytostatic hor mone ther apy 23% 

drugs used in di a be tes 16% 

ant ac ids/antiflatulents/antiulcerants 13% 

hor mones pi tu itary and hy po tha lamic 1% 

Lead ing Dose Forms: 

tab lets 61% 

vi als 24% 

cap sules 13% 

coated tab lets 2% 

� CHINA 

TIANJIN TAKEDA 

Full Name: Tianjin Takeda Pharmaceuticals Co., 

Ltd 

Street Ad dress: No. 11, Xinghua Road, Tianjin 

Xiqing, Eco nomic De vel op ment Area, Tianjin 

Tel: +86 22 23970011 

Fax: +86 22 23972230 

De scrip tion: De vel oper, man u fac turer, for mu la - 

tor, packager/as sem bler, im porter, ex porter, pro - 

moter, sales/detailer. Prod uct ranges in clude: 

phar ma ceu ti cal prod ucts (branded, pre scrip tion). 

Established 1994. 

Con tacts (Pharm): Chair man: Shun Baowei; 

Com mer cial Op er a tions: Philip Huang; Man u fac - 

ture: Yukio Araki; Mar ket Re search: Shan Yong; 

Re search & De vel op ment: Lilly Liang; Gen eral 

Con tact: Hideyuki Matsumoto 

Sub sid iary of: Takeda, Ja pan (75%) 

� FRANCE 

TAKEDA 

Full Name: Laboratoires Takeda 

Street Ad dress: 15 Quai de Dion Bou ton, 92 816 

Puteaux Cedex 

Tel: +33 1 46 25 16 16 

Fax: +33 1 46 97 00 11 

Email: con tact_com mu ni ca tion@labo-takeda.fr 

Home Page: www.takeda.fr 

De scrip tion: De vel oper, im porter, ex porter, pro - 

moter, sales/detailer, packager/as sem bler, dis - 

trib u tor. Prod uct ranges in clude: phar ma ceu ti cal 

prod ucts (branded, pre scrip tion, non-pre scrip - 

tion), hos pi tal pharmaceuticals. Es tab lished 1978. 

480 phar ma ceu ti cal employees in 2006. 


ber): 320 (2006) 

Con tacts (Pharm): Chair man: Yves Lepine; 

Com mer cial Op er a tions: Alexandre Beithelot; 



Mar ket Re search: Michel Mauvetu; Re search & 

De vel op ment: Aszi Beukritly 

Sub sid iary of: Takeda, Neth er lands (100%) 


Prod ucts (% of Sales by Lead ing 5): 80-85% 


5): 95-100% 



ENANTONE (cytostatic hor mone) 


KENZEN (an gio ten sin-II an tag o nist plain) 

OGAST (antiulcerant) 

COKENZEN (an gio ten sin-II an tag o nist com bi na - 

tion) 






antibacterials sys temic 1% 


tab lets 55% 

vi als 25% 

cap sules 15% 


� GERMANY 

TAKEDA PHARMA 

Full Name: Takeda Pharma GmbH 

Street Ad dress: Viktoriaallee 3-5, D-52066 

Aachen 

Tel: +49 241 941-0 

Fax: +49 241 941-2769 

Email: info@takeda.de 

Home Page: www.takeda.de 

De scrip tion: De vel oper, ex porter, pro moter, 

sales/detailer. Prod uct ranges in clude: phar ma - 

ceu ti cal prod ucts (branded, pre scrip tion). Es tab - 

lished 1981. 

Con tacts (Pharm): Chair man: Noriaki Hada, 

Guenter Jo sephs; Com mer cial Op er a tions: 

Mathias Bosch; Mar ket Re search: Norbert 

Sarnes; Re search & De vel op ment: Reinhold 

Huebner 

Par ent of: Takeda Pharma, Aus tria (100%); 

Takeda Pharma, Swit zer land (100%). 





5): 95-100% 



TRENANTONE (cytostatic hor mone) 


bi na tion) 



COMPETACT (antidiabetic oral) 





hor mones pi tu itary and hy po tha lamic 3% 



tab lets 54% 

pre-filled sy ringes/pens 37% 


cap sules 2% 

� INDONESIA 

TAKEDA 

Full Name: PT Takeda In do ne sia 

Street Ad dress: Plaza DM 15th Fl., Jl Jend. 

Sudirman Kav.25, Ja karta 12920 

Tel: +62 21 5267656 

Fax: +62 21 5267657 

De scrip tion: Man u fac turer, ex porter, pro moter. 

Prod uct ranges in clude: phar ma ceu ti cal prod ucts 

(branded, pre scrip tion, non-pre scrip tion). Es tab - 

lished 1971. 313 phar ma ceu ti cal employees in 

2007. 


ber): 101-500 (2007) 

Con tacts (Pharm): Chair man: Hiromasa 

Okada; Com mer cial Op er a tions: Bahori Pohan 

(Sales); Man u fac ture: Alex M.T; Gen eral Con tact: 

Herlina Choirunnisa 





5): 70-75% 

Dose Forms (% of Sales by Lead ing 5): 

95-100% 


VITACIMIN (vi ta min C plain/com bi na tion with 

min er als) 




NONFLAMIN (an al ge sic non-nar cotic) 

PROSOGAN FD (antiulcerant) 

NICHOLIN (ce re bral/pe riph eral vasotherapeutic) 


vi ta mins 29% 


an al ge sics 11% 


antibacterials sys temic 8% 


tab lets 62% 

am poules 12% 

cap sules 11% 

vi als 10% 

sup pos i to ries 3% 

� IRELAND 

TAKEDA 

Full Name: Takeda Ire land Ltd 

Street Ad dress: Bray Busi ness Park, Kilruddery 

Co Wicklow 

Tel: +353 1 2050600 

Fax: +353 1 2050601 

Home Page: www.takeda.ie 

De scrip tion: De vel oper, man u fac turer, for mu la - 

tor, packager/as sem bler, ex porter. Man u fac tures 

for other com pa nies. Prod uct ranges in clude: 


Es tab lished 1997. 420 phar ma ceu ti cal employees 

in 2007. 


ber): 0 (2007) 

Con tacts (Pharm): Man u fac ture: Paul Blunnie; 

Gen eral Con tact: Tony Grannell 


TAKEDA PHARMA 

Full Name: Takeda Pharma Ire land Lim ited (TPI) 

Street Ad dress: Grange Cas tle Busi ness Park, 

Dub lin 22 

Tel: +353 1 4672400 

Fax: +353 1 4672401 

Email: tpiinfo@takeda.ie 

Home Page: www.takeda.ie 

De scrip tion: Man u fac turer. Prod uct ranges in - 

clude: phar ma ceu ti cal prod ucts (branded, pre - 

scrip tion), fine chem i cals. Es tab lished 2002. 50 

phar ma ceu ti cal employees in 2006. 


ber): 0 (2006) 

Con tacts (Pharm): Chair man: Yoshiharu Maeda 


� ITALY 

TAKEDA 

Full Name: Takeda Italia Farmaceutici SpA 

Street Ad dress: Via Elio Vittorini, 129, 00144 

Roma 

Tel: +39 06 502601 

Fax: +39 06 5011709 

De scrip tion: Re searcher, de vel oper, man u fac - 

turer, im porter, dis trib u tor, pro moter, 

sales/detailer, packager/as sem bler. Prod uct 

ranges in clude: phar ma ceu ti cal prod ucts 

(branded, pre scrip tion). Es tab lished 1982. 664 

phar ma ceu ti cal employees in 2007. 


ber): 101-500 (2007) 

Con tacts (Pharm): Chair man: Dr S. Maurizio 

Castorina; Com mer cial Op er a tions: Dr Paolo La 

Commare; Man u fac ture: Dr Pierfelice Ferrari; 

Mar ket Re search: Dr Arnaldo Scarrone; Re search 

& De vel op ment: Dr Cinzia Di Pietro; Gen eral Con - 

tact: Ornella Gallo 

Sub sid iary of: Takeda, Neth er lands (76.92%) 




5): 95-100% 


95-100% 


LANSOX (antiulcerant) 


BLOPRESID (an gio ten sin-II an tag o nist com bi na - 

tion) 

ENANTONE DE POT (cytostatic hor mone) 







cal cium an tag o nists 5% 


tab lets 57% 

cap sules 24% 

vi als 14% 


pow ders/gran ules - 



� JAPAN 

AMATO 

Full Name: Amato Phar ma ceu ti cal Prod ucts Ltd 

Street Ad dress: 995 Sasao-cho, 

Fukuchiyama-shi, Kyoto 620-0932 

Tel: +81 77 322 1100 

Fax: +81 77 323 3355 




95-100% 


5): n.a. 



BORRAGINOL (antihemorrhoidal top i cal; var i cose 

ther apy sys temic) 

BORRAZA G (antihemorrhoidal top i cal) 

HEMOCURON (var i cose ther apy sys temic) 


antivaricosis/antihemorrhoidal prep a ra tions 

100% 


oint ments 64% 

sup pos i to ries 32% 

cap sules 3% 

pow ders/gran ules 2% 

NIHON PHARMACEUTICALS 

Full Name: Nihon Phar ma ceu ti cal Co. Ltd. 

Street Ad dress: 9-8, Higashikanda 1-chome, 

Chiyoda-ku, To kyo 101-0031 

Tel: +81 3 3864 8411 

Fax: +81 3 5687 9485 

Home Page: www.nihon-pharm.co.jp 

Sub sid iary of: Takeda, Ja pan (87.5%) 




5): 85-90% 


95-100% 


GLOVENIN I (im mu no glob u lin G IV) 

NONTHRON KENKETU (proteinase in hib i tor) 

AL BU MIN NICHIYAKU (pro tein so lu tion) 

ALBUMINATE NICHIYA (pro tein so lu tion) 

OSVAN (an ti sep tic/dis in fec tant) 


sera/gammaglobulins 51% 

antihemorrhagics 16% 

blood/plasma sub sti tutes 12% 

IV so lu tions over 100cc 6% 

an ti sep tics and dis in fec tants 4% 


vi als 79% 

in fu sions 11% 


liq uids 4% 

tab lets 2% 

TAKEDA 

Full Name: Takeda Phar ma ceu ti cal Com pany 

Lim ited 

Street Ad dress: 1-1 Doshomachi 4-chome, 

Chuo-ku, Osaka 540-8645 

Tel: +81 6 6204 2111 

Fax: +81 6 6204 2880 

Home Page: www.takeda.co.jp 

De scrip tion: Man u fac turer, re searcher, de vel - 

oper, im porter, ex porter, dis trib u tor, pro moter. 

De vel ops, dis trib utes for other com pa nies. Prod - 

uct ranges in clude: phar ma ceu ti cal prod ucts 

(branded, pre scrip tion, non-pre scrip tion), in ter - 

me di ates, di ag nos tic prod ucts, med i cal equip - 

ment, vet er i nary pharmaceuticals. Es tab lished 

1925. 14,993 phar ma ceu ti cal em ploy ees in 2007. 

Di vi sions in clude: Pharmaceuticals; Vitamin & 

Food (bulk vitamins); Chemical Products. 

Con tacts (Pharm): Chair man: Yasuchika 

Hasegawa; Com mer cial Op er a tions: Makoto 

Yamaoka; Man u fac ture: Akira Nakatani; Re - 

search & De vel op ment: Dr Shigenori Ohkawa 

(Phar ma ceu ti cal Re search), Dr Masaomi 

Miyamoto (Phar ma ceu ti cal De vel op ment); Gen - 

eral Contact: Takaharu Nishida 

Par ent of: Tianjin Takeda, China (75%); Takeda, 

In do ne sia (70%); Takeda, Ire land (100%); 

Takeda Pharma, Ire land (100%); Amato, Ja pan 

(30%); Nihon Pharmaceuticals, Ja pan (87.5%); 

Wako Pure Chem i cal In dus tries, Ja pan (70.3%); 

Takeda, Neth er lands (100%); Boie-Takeda, Phil - 

ip pines (50%); Green Cross, Sin ga pore (12%); 

Takeda, Tai wan (100%); Takeda, Thai land 

(48%); Par a digm Ther a peu tics, UK; Mil len nium, 

USA (100%) (ac quired 2008); Takeda Amer ica 

Holdings, USA (100%). 

Phar ma ceu ti cal Sales: US$ 4,200-4,300 mil - 

lion 



5): 75-80% 


95-100% 





TAKEPRON (antiulcerant) 

LEUPLIN (cytostatic hor mone; hor mone hy po tha - 

lamic) 

BASEN (antidiabetic oral) 







vi ta mins 5% 


tab lets 63% 

pre-filled sy ringes/pens 13% 


vi als 6% 

cap sules 3% 

WAKO PURE CHEM I CAL IN DUS TRIES 

Full Name: Wako Pure Chem i cal In dus tries, Ltd. 

Street Ad dress: 1-2, Doshomachi 3-chome 

Chuo-ku, Osaka 541-0045 

Tel: +81 6 6203 3741 

Fax: +81 6 6203 2029 

Home Page: www.takeda.co.jp 

De scrip tion: Pre vi ously known as Takeda To kyo. 

Sub sid iary of: Takeda, Ja pan (70.3%) 

� NETHERLANDS 

TAKEDA 

Full Name: Takeda Eu rope Hold ings B.V. 

Street Ad dress: WTC Am ster dam A-12, 

Strawinskylaan 1217, 1077 XX Am ster dam 

De scrip tion: Hold ing com pany. 

Par ent of: Takeda, France (100%); Takeda 

Pharma, Ger many (100%); Takeda, It aly 

(76.92%); Takeda, UK (100%); Takeda Cam - 

bridge, UK (100%); Takeda Global R&D, UK 

(100%); Takeda Pharma, UK (100%). 


� PHILIPPINES 

BOIE-TAKEDA 

Full Name: Boie-Takeda Chem i cals Inc 

Street Ad dress: 12/F, Sky Plaza Bldg., 6788 

Ayala Av e nue, Oledan Square, Makati City 

Tel: +63 2 886-69-54/61 

Fax: +63 2 886-69-41 

Email: takeda@boie-takeda.com 

De scrip tion: De vel oper, dis trib u tor. Prod uct 


(branded, pre scrip tion), oph thal mic prod ucts. Es - 

tab lished 1968. 135 phar ma ceu ti cal employees in 

2007. 


ber): 85 (2007) 

Con tacts (Pharm): Chair man: Nick A. Lansang; 

Com mer cial Op er a tions: Ed Kanap(Sales), Edwin 

Villavieva (Mar ket ing); Re search & De vel op ment: 

Asuncion Sayson; Gen eral Con tact: Chris tine 

Abonguey 

Sub sid iary of: Boie, Phil ip pines (50%); Takeda, 

Ja pan (50%) (group: Takeda, Ja pan) 




5): 90-95% 


95-100% 


PREVACID (antiulcerant) 




bi na tion) 

LUPROLEX (cytostatic hor mone) 






vi ta mins 6% 


tab lets 71% 

vi als 11% 

cap sules 7% 


am poules 4% 

� SINGAPORE 

GREEN CROSS 

Full Name: Green Cross Pharma Pte Ltd 

Street Ad dress: 63 Hillview Ave, 08-18 Lam 

Soon In dus trial Bldg, Sin ga pore 669569 

Tel: +65 6 7630388 

Fax: +65 6 7634676 

Email: sales@greencross.com.sg 

De scrip tion: Im porter, ex porter, dis trib u tor, 

pro moter, sales/detailer. Im ports, ex ports, dis - 



trib utes, pro motes, sells/de tails for other com pa - 

nies. Prod uct ranges in clude: phar ma ceu ti cal 

prod ucts (branded, unbranded, pre scrip tion, 

non-pre scrip tion), hos pi tal pharmaceuticals, 

med i cal equip ment, med i cal sup plies, oph thal mic 

prod ucts. Es tab lished 1980. 12 pharmaceutical 

employees in 2007. 


ber): 1-10 (2007) 

Con tacts (Pharm): Chair man: George H. Rott 




95-100% 


5): 95-100% 


95-100% 


ALBUTEIN (pro tein so lu tion) 

DIOSPER (var i cose ther apy sys temic) 

BECLO-ASMA (corticoid) 

BUTO-ASMA (B2-stim u lant) 

UROKINASE (fibrinolytic) 


blood/plasma sub sti tutes 86% 

antiasthma and COPD prod ucts 6% 

antivaricosis/antihemorrhoidal prep a ra tions 

6% 

antithrombotic agents 1% 

emol lients/protectives 1% 


in fu sions 86% 

pres sur ised aero sols 6% 

tab lets 6% 

vi als 1% 

liq uids 1% 

� SWITZERLAND 

TAKEDA PHARMA 

Full Name: Takeda Pharma AG 

Postal Ad dress: Postfach, CH-8853 Lachen 

Street Ad dress: Alpenblickstrasse 26, CH-8853 

Lachen 

Tel: +41 55 451 52 00 

Fax: +41 55 451 52 20 

Email: info@takeda.ch 

Home Page: www.takeda.ch 

De scrip tion: Pro moter, sales/detailer. Prod uct 


(branded, pre scrip tion). Es tab lished 1998. 43 

phar ma ceu ti cal em ploy ees in 2007. Di vi sions in - 

clude: Gastroenterology; Car di ol ogy; Diabetes. 


ber): 21-50 (2007) 

Con tacts (Pharm): Chair man: Jean-Luc De lay; 

Com mer cial Op er a tions: Bruno Faerber, Ernst 

Meier; Gen eral Con tact: Jean-Luc Delay 

Sub sid iary of: Takeda Pharma, Ger many 

(100%) 



95-100% 


5): n.a. 



AGOPTON (antiulcerant) 



bi na tion) 







psychoanaleptics 1% 


tab lets 69% 

cap sules 29% 


� TAIWAN 

TAKEDA 

Full Name: Takeda Chem i cal In dus tries (Tai wan) 

Ltd 

Street Ad dress: 7th Floor, Great China Build ing, 

No 217, Sec 3, Nan king East Road, Tai pei 

Tel: +886 2 2712-1112 

Fax: +886 2 2712-1118 

De scrip tion: Im porter, pro moter, sales/detailer. 

Prod uct ranges in clude: phar ma ceu ti cal prod ucts 

(branded), hos pi tal pharmaceuticals. Es tab lished 

1962. 107 phar ma ceu ti cal em ploy ees in 2006. 


ber): 77 (2006) 

Con tacts (Pharm): Chair man: Stan ley Lee; 

Com mer cial Op er a tions: PoPo Lin, Jackie Tieng; 

Man u fac ture: Mr J.D. Wu; Re search & De vel op - 

ment: Grace Fang; Gen eral Con tact: Mr C.C. Kuo 







5): 85-90% 


95-100% 



TAKEPRON OD (antiulcerant) 


LEUPLIN DE POT (cytostatic hor mone) 

SHIN BIOFERMIN S (antidiarrheal mi cro-or gan - 

ism) 






antidiarrheals, elec tro lyte re plac ers, in tes ti nal 

anti-inflammatorie s 8% 


tab lets 75% 

vi als 15% 


cap sules 2% 


� THAILAND 

TAKEDA 

Full Name: Takeda (Thai land) Ltd 

Street Ad dress: 10th Floor, Rajanakarn Bldg., 

183 South Sathorn Road, Kwang Yannawa, Khet 

Sathorn, Bang kok 10120 

Tel: +66 2 676 6770 

Fax: +66 2 676 6770 





5): 90-95% 


95-100% 



MADIPLOT (cal cium an tag o nist plain) 



ENANTONE L.P. (cytostatic hor mone) 




cal cium an tag o nists 21% 




tab lets 88% 

vi als 10% 


liq uids 1% 

am poules - 

� UK 

MIL LEN NIUM 

Full Name: Mil len nium Pharmaceuticals, Ltd. 

Street Ad dress: Build ing 3, Chis wick Park, 566 

Chis wick High Road, Chis wick, Lon don, W4 5YA 

Tel: +44 20 8849 8060 

Fax: +44 20 8849 5580 

Email: info_eu@mlnm.com 

Home Page: www.mlnm.com 

De scrip tion: Re searcher. Prod uct ranges in - 

clude: phar ma ceu ti cal prod ucts, di ag nos tic prod - 

ucts. Es tab lished 2000. 

Con tacts (Pharm): Chair man: Dr Alan 

Marchington; Com mer cial Op er a tions: Sean 

Cush; Re search & De vel op ment: Dr Da vid 

Tapolczay; Gen eral Con tact: Julia Wilson 

Sub sid iary of: Mil len nium, USA 

TAKEDA 

Full Name: Takeda UK Ltd 

Street Ad dress: Takeda House, Mer cury Park, 

Wycombe Lane, Wooburn Green, High Wycombe, 

Buckinghamshire HP10 0HH 

Tel: +44 1628 537900 

Fax: +44 1628 526615 

Home Page: www.takeda.co.uk 

De scrip tion: De vel oper, dis trib u tor, pro moter, 

sales/detailer. Prod uct ranges in clude: phar ma - 

ceu ti cal prod ucts (branded, pre scrip tion), hos pi tal 

pharmaceuticals. Es tab lished 1997. 

Con tacts (Pharm): Chair man: An drew Da vis; 

Com mer cial Op er a tions: Mark Mor ri son, Trevor 

Smith; Mar ket Re search: Mark Mor ri son; Re - 

search & De vel op ment: Jay Herbert 




95-100% 


5): n.a. 





AMIAS (an gio ten sin-II an tag o nist plain) 







tab lets 97% 


TAKEDA CAM BRIDGE 

Full Name: Takeda Cam bridge Lim ited 

Street Ad dress: 418 Cam bridge Sci ence Park, 

Cam bridge, Cam bridge shire CB4 0PA 

Tel: +44 1223 477910 

Fax: +44 1223 477911 


TAKEDA GLOBAL R&D 

Full Name: Takeda Global Re search & De vel op - 

ment Cen tre (Eu rope) Ltd. 

Street Ad dress: Arundel Great Court, 2 Arundel 

Street, Lon don, WC2R 3DA 

Tel: +44 20 7759 5000 

Fax: +44 20 7759 5270 

De scrip tion: Es tab lished 1994. Pre vi ously 

known as Takeda Euro R&D. 


TAKEDA PHARMA 

Full Name: Takeda Pharmaceuticals Eu rope Lim - 

ited 

Street Ad dress: 55 New Ox ford Street, Lon don, 

WC1A 1BS 

Tel: +44 20 7632 9300 

Fax: +44 20 7632 9309 

De scrip tion: Hold ing com pany. Es tab lished 

1998. Pre vi ously known as Takeda Eu rope Hold - 

ings. 

Con tacts (Pharm): Chair man: Giacomo De 

Nepi; Com mer cial Op er a tions: Da vid Rob erts 


� USA 

MIL LEN NIUM 

Full Name: Mil len nium Pharmaceuticals Inc 

Street Ad dress: 40 Landsdowne Street, Cam - 

bridge, Mas sa chu setts 02139 

Tel: +1 617 679 7000 

Fax: +1 617 374 7788 

Email: info@mlnm.com 

Home Page: www.mlnm.com 

De scrip tion: Re searcher, de vel oper, 

sales/detailer. Re searches, de vel ops for other 

com pa nies. Prod uct ranges in clude: phar ma ceu ti - 

cal prod ucts (branded, pre scrip tion), hos pi tal 

pharmaceuticals, bio tech nol ogy prod ucts, di ag - 

nos tic prod ucts. Established 1993. 

Con tacts (Pharm): Chair man: Mark J. Levin; 

Com mer cial Op er a tions: Theresa McNeely; Man u - 

fac ture: James Nash; Re search & De vel op ment: 

Charles Homcy, Rob ert Tepper, Dr Jo seph Bolen; 

Gen eral Con tact: Clare Midgely 

Par ent of: Mil len nium, UK. 

Sub sid iary of: Takeda, Ja pan (100%) (ac quired 

2008) 



95-100% 


5): n.a. 



VELCADE (antineoplastic other) 


antineoplastics 100% 


vi als 100% 

TAKEDA 

Full Name: Takeda Pharmaceuticals North 

Amer ica, Inc. 

Street Ad dress: One Takeda Park way, 

Deerfield, Il li nois 60015 

Tel: +1 224 554 6500 

Email: busdev@tpna.com 

Home Page: www.tpna.com 

De scrip tion: Re searcher, de vel oper, for mu la tor, 

pro moter, sales/detailer. Pro motes, sells/de tails 

for other com pa nies. Prod uct ranges in clude: 


Es tab lished 1998. 3,183 phar ma ceu ti cal 

employees in 2007. 


ber): over 2,001 (2007) 

Con tacts (Pharm): Chair man: Mark Booth; 

Com mer cial Op er a tions: Dan iel Or lando (Sales), 

An drew Hull (Mar ket ing); Re search & De vel op - 

ment: Dr Mehmood Khan; Gen eral Con tact: 

Matthew Kuhn 

Par ent of: Takeda Global R&D, USA (100%). 

Sub sid iary of: Takeda Amer ica Hold ings, USA 

(100%) 



Phar ma ceu ti cal Sales: US$ 7,200-7,300 mil - 

lion 


95-100% 


5): 95-100% 


95-100% 




PREVACID SOLUTAB (antiulcerant) 

ACTOPLUS MET (antidiabetic oral) 

AMITIZA (lax a tive) 




lax a tives 3% 

psycholeptics 2% 

anti rheu ma tics sys temic - 


tab lets 48% 

cap sules 44% 


pow ders/gran ules - 

vi als - 

TAKEDA AMER ICA HOLD INGS 

Full Name: Takeda Amer ica Hold ings Inc 

Street Ad dress: 767 Third Av e nue, 8th Floor, 

New York, New York 10017 

Tel: +1 212 421 6954 

Fax: +1 212 355 5243 

De scrip tion: Hold ing com pany. 

Par ent of: Takeda, USA (100%); Takeda Re - 

search, USA (100%); TAP, USA (100%). 


TAKEDA GLOBAL R&D 

Full Name: Takeda Global Re search & De vel op - 

ment Cen ter Inc. 

Street Ad dress: One Takeda Park way, 

Deerfield, Il li nois 60015 

Tel: +1 224 554 6500 

Sub sid iary of: Takeda, USA (100%) 

TAKEDA RE SEARCH 

Full Name: Takeda Re search In vest ment, Inc. 

Street Ad dress: 435 Tasso Street, Suite 300, 

Palo Alto, Cal i for nia 94301 

Tel: +1 650 328 2900 

Fax: +1 650 328 2922 

Email: con tact@tri-takeda.com 

Home Page: www.tri-takeda.com 

Con tacts (Pharm): Chair man: Koichi Kato 


(100%) 

TAP 

Full Name: TAP Pharmaceuticals Inc 

Street Ad dress: 675 North Field Drive, Lake For - 

est, Il li nois 60045 

Tel: +1 847 582 2000 

Fax: +1 847 582 5797 

Home Page: www.tap.com 

De scrip tion: Re searcher, de vel oper, dis trib u tor, 

pro moter, sales/detailer. Prod uct ranges in clude: 


Es tab lished 1985. 

Con tacts (Pharm): Chair man: Tom Watkins; 

Com mer cial Op er a tions: Don Meek, Art Rice; Mar - 

ket Re search: Alan Gordon; Re search & De vel op - 

ment: Xa vier Frapaise 


(100%) 


IMS COM PANY PRO FILES APPENDIX - CURRENT COMPANY PROFILES 

Appendix - Current Company Profiles 

� AMER ICAS 

Apotex Can ada 

Biovail Can ada 

Abbott USA 

Allergan USA 

Amgen USA 

Barr USA 

Bausch & Lomb USA 

Baxter In ter na tional USA 

Biogen IDEC USA 

Bris tol-Myers Squibb USA 

Cephalon USA 

Eli Lilly USA 

Endo Pharmaceuticals USA 

For est Lab o ra tories USA 

Genentech USA 

Genzyme USA 

Gilead USA 

Hu man Ge nome Sci ences USA 

Isis USA 

John son & John son USA 

King USA 

Merck & Co USA 

Mil len nium USA 

Mylan USA 

Par Pharmaceuticals USA 

Pfizer USA 

Procter & Gam ble USA 

Schering-Plough USA 

Sepracor USA 

Valeant USA 

Wat son USA 

Wyeth USA 

� ASIA 

Dr Reddy's India 

Ranbaxy India 

Astellas Japan 

Chugai Ja pan 

Daiichi Sankyo Ja pan 

Dainippon Sumitomo Japan 

Eisai Ja pan 

Kowa Japan 

Kyowa Hakko Japan 

Meiji Seika Japan 

Mitsubishi Tanabe Japan 

Ono Japan 

Otsuka Ja pan 

Shionogi Ja pan 

Taisho Ja pan 

Takeda Ja pan 

� EU ROPE 

Sol vay Bel gium 

UCB Bel gium 

Zentiva Czech Republic 

LEO Pharma Den mark 

Lundbeck Den mark 

Novo Nordisk Den mark 

Ipsen France 

Pi erre Fabre France 

sanofi-aventis France 

Servier France 

Bayer Ger many 

Boehringer Ingelheim Ger many 

Gruenenthal Ger many 

Fresenius Germany 

Merck KGaA Ger many 

ratiopharm Germany 

Stada Germany 

Gedeon Rich ter Hun gary 

Actavis Iceland 

Elan Ire land 

Teva Is rael 

Chiesi It aly 

Menarini It aly 

Recordati It aly 

Sigma-Tau It aly 

Almirall Spain 

Esteve Spain 

Ferring Switzerland 

Mundipharma Switzerland 

Nes tle Swit zer land 

Novartis Swit zer land 

Roche Swit zer land 

Nycomed Pharma Switzerland 

Acambis UK 

AstraZeneca UK 

GlaxoSmithKline UK 

Shire UK 

SkyePharma UK 

Vernalis UK

IMS Company Profiles - Report Buyer

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