IMS Company Profiles - Report Buyer

IMS COM PANY PRO FILES TAKEDA
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.
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