AstraZeneca Annual Report and Form 20-F Information 2011

In the pipelineDapagliflozin, an investigational compound, is a potential first-in-classSGLT2 inhibitor under joint development with BMS as a once-dailyoral therapy for the treatment of adult patients with Type 2 diabetes.In March 2011, the FDA accepted for review the NDA filed byAstraZeneca and BMS for dapagliflozin as a once-daily oral therapyfor the treatment of adult patients with Type 2 diabetes. In June,AstraZeneca and BMS announced the results of two Phase III trialsthat showed that dapagliflozin treatment was effective in loweringblood glucose and body weight as initial combination therapy withmetformin in drug-naïve Type 2 diabetes patients with poor glycemiccontrol. In addition, long-term (102 week) data from double-blindextensions of two Phase III studies in Type 2 diabetes patients showedthat improvements in blood glucose lowering and weight loss weremaintained over two years for dapagliflozin added to metformin.In July, AstraZeneca and BMS reported the outcome of the FDAAdvisory Committee meeting on the NDA. On the question ‘Do theefficacy and safety data provide substantial evidence to supportapproval of dapagliflozin as an adjunct to diet and exercise toimprove glycemic control in adults with Type 2 diabetes mellitus?’,the committee voted against recommending approval by nine ‘no’votes to six ‘yes’. AstraZeneca and BMS subsequently submittedadditional clinical data to support the FDA’s review of dapagliflozin.This submission represented a major amendment to the NDA andresulted in a three-month extension to the PDUFA action date toJanuary 2012.In January 2012, AstraZeneca and BMS received a CompleteResponse Letter from the FDA requesting additional clinical data toallow a better assessment of the benefit/risk profile for dapagliflozin.This includes clinical trial data from ongoing studies and may requireinformation from new clinical trials. AstraZeneca and BMS will workclosely with the FDA to determine the appropriate next steps for thedapagliflozin application and remain committed to its development.In November, AstraZeneca and BMS announced results from apre-specified meta-analysis of CV safety data from 14 Phase IIb/IIItrials in adult patients with Type 2 diabetes. These showed thatdapagliflozin was not associated with an unacceptable increase inCV risk relative to all comparators pooled in the clinical programme.The review of the MAA for dapagliflozin in the EU is in progress witha decision expected by the second quarter of 2012.Our activities in the glucokinase activator area were discontinuedduring 2011 based on Phase IIb data not showing results supportingthe intended target product profile (TPP). In addition, during 2011,we discontinued AZD8329 and AZD7687 due to clinical results notsupporting the intended TPP. In 2011, AZD2820 was initiated in clinicaltesting for the treatment of obesity.Atrial fibrillationAtrial fibrillation (AF) is the most common cardiac arrhythmia.Rhythm-control therapy to manage the symptoms of AF is dominatedby generic amiodarone, which is effective at maintaining patientsin normal heart rhythm but very poorly tolerated. AF is associatedwith an increased risk of cerebral embolism resulting in stroke anddisability. To reduce the risk of such AF-related complications,anti-coagulation with vitamin K antagonists can be used. Newanti-coagulation therapies with improved convenience are emerging.In the pipelineFor the control of heart rhythm in AF, our focus is on atrial-specificagents as a way to reduce the risk of pro-arrhythmic effects. Ouractivities in this area are primarily in preclinical development, withAZD2927 recently entering Phase II.Financial performance 2011/2010Performance 2011Reported performanceCV sales grew by 9% to $10,212 million, up from $9,403 million in2010, driven by the continuing growth in Crestor.Performance – CER growth ratesCV sales increased by 5%.Global sales of Crestor increased by 13% to $6,622 million. USCrestor sales increased by 16% to $3,074 million. A competitor toCrestor, atorvastatin (Lipitor), was available in generic form in theUS from late 2011.Crestor sales outside the US increased by 10% to $3,548 million.Volume growth for Crestor in these markets continues to significantlyexceed the growth in the overall statin market. Sales in Western Europeincreased by 5%, largely due to double digit growth in France andSpain. Sales in Established ROW increased by 15%. Sales in EmergingMarkets increased by 8%, where good growth in China was partiallyoffset by generic erosion in Brazil.US sales of the Toprol-XL product range, which includes sales ofthe authorised generic, decreased by 41% to $404 million, due todeclining prescription volume and lower prices. An additional genericproduct received regulatory approval in December.Sales of Seloken in other markets increased by 8% to $582 million,with a 15% increase in Emerging Markets.US Atacand sales decreased by 16%. Outside the US, Atacand salesdecreased by 4%.Alliance revenue from the Onglyza TM collaboration with BMS totalled$211 million, with alliance revenue in the US of $156 million and$55 million in other markets.Brilinta/Brilique sales were $21 million.Performance 2010Reported performanceCV sales grew by 12% to $9,403 million in 2010 from $8,376 millionin 2009, driven by the continuing growth in Crestor.Performance – CER growth ratesCV sales were up 11%.Global sales of Crestor were up 24%. US sales for Crestor increasedby 26% to $2,640 million. Crestor sales outside the US were up 23% to$3,051 million, with sales in Established ROW up 25%, including goodgrowth in Canada (25%), Japan (25%) and Other Established ROW(23%). Sales in Western Europe were up 20%, driven by good growthin France, Italy and Spain. Sales in Emerging Markets were up 26%.Sales of Seloken/Toprol-XL decreased by 17%. US sales of theToprol-XL product range, which includes sales of the authorisedgeneric, decreased by 29% to $689 million as a result of furthergeneric competition, although this was partially offset by 13%growth in Emerging Markets to $391 million.Atacand sales were up 3%, despite US sales being down 18%, asa result of strong growth in Established ROW (8%) and EmergingMarkets (17%).Alliance revenue from the Onglyza collaboration with BMS totalled$69 million, comprising $54 million in the US and $15 million inother markets.Business ReviewAstraZeneca Annual Report and Form 20-F Information 2011Therapy Area Review Cardiovascular 61