AstraZeneca Annual Report and Form 20-F Information 2011

Therapy Area ReviewIn September, we announced the European Society of Cardiology(ESC) included Brilique on their non-ST elevation myocardial infarction(NSTEMI) guidelines in a 1st line position ahead of clopidogrel. Thissupports its earlier inclusion in the ESC/EACTS revascularisationguidelines in 2010.In November, Brilinta received a Class I recommendation in theupdated percutaneous coronary intervention (PCI) guidelines fromthe American Heart Association (AHA), the American College ofCardiology Foundation (ACCF) and the Society for CardiovascularAngiography and Interventions (SCAI). That month Brilinta was alsoadded to the updated AHA/ACCF Coronary Artery Bypass Graft(CABG) and Secondary Prevention & Risk Reduction Guidelines.Brilinta/Brilique remains under regulatory review in 39 countries. It hasbeen approved in 64 countries, including in the US, Canada and Brazilunder the trade name Brilinta and in the EU, Iceland and Norway,under the trade name Brilique. Additional marketing authorisationsand regulatory submissions are planned for 2012.Atacand continues to be an important treatment option for patientswith hypertension and symptomatic heart failure. Atacand is approvedfor the treatment of hypertension in over 125 countries and forsymptomatic heart failure in more than 70 countries. Most patientswith hypertension fail to reach their treatment goals with the use ofa single anti-hypertensive treatment and fixed dose combinations oftwo or more anti-hypertensives are commonly prescribed for patientsto improve efficacy and attainment of treatment goals. Atacand Plus(candesartan cilexetil/hydrochlorothiazide) is a fixed dose combinationof Atacand and the diuretic hydrochlorothiazide, indicated for thetreatment of hypertension in patients who require more than oneanti-hypertensive therapy. Atacand Plus is approved in 98 countries.Axanum is a single capsule of low-dose ASA and esomeprazole (theactive ingredient in Nexium). It is indicated for prevention of CV eventsin high-risk CV patients in need of daily low-dose ASA treatment andwho are at risk of gastric ulcers. Low-dose ASA is a mainstay oftherapy for patients at high risk of having a CV event such as a heartattack or stroke. Up to 30% of patients with upper gastrointestinalproblems discontinue or take deliberate breaks from their low-doseASA treatment, placing them at risk of a potentially life-threateningCV event as early as eight to 10 days after discontinuation.In May, AstraZeneca received a Complete Response Letter from theFDA for the NDA for Axanum. AstraZeneca has worked with the FDAand provided additional information. Due to the time delay caused bythe Complete Response Letter and the additional review, AstraZenecahas decided to withdraw the NDA for Axanum.In August, Axanum received positive agreement for approval in 23European member states and in Norway. Axanum has been approvedin 13 of these countries and its first market launch occurred inGermany in November.Clinical studies of our key marketed productsGALAXY, our long-term global clinical research programme forCrestor, investigates links between optimal lipid control, atherosclerosisand CV morbidity and mortality. The programme has completed anumber of studies involving over 65,000 patients in over 55 countries,some of which are referred to below.The SATURN study was designed to measure the impact of Crestor40mg and atorvastatin (Lipitor) 80mg on the progression ofatherosclerosis in high-risk patients. Results from the SATURN studypublished in November did not demonstrate a statistically significantgreater reduction in favour of Crestor versus atorvastatin (Lipitor)on the primary endpoint of percent atheroma volume, even thoughthe reduction was numerically greater. For the secondary efficacymeasure of normalised total atheroma volume (TAV), Crestordemonstrated a statistically significant reduction compared withatorvastatin (Lipitor). Statistically significant differences wereobserved in favour of Crestor for key lipid parameters, and, onceagain, the study demonstrated that Crestor helps to reduce plaquebuild-up in the arteries.In October 2010, AstraZeneca initiated PEGASUS TIMI-54, a 21,000patient study in over 30 countries. The study examines the abilityof Brilinta/Brilique plus aspirin to prevent adverse CV events safelycompared to aspirin alone in higher-risk patients one to three yearsafter a heart attack. Enrolment for PEGASUS began in December2010 and is ongoing.The ATLANTIC trial started recruitment in September and is designedto examine the efficacy of pre-hospital (eg ambulance) versusin-hospital administration of Brilinta/Brilique co-administered withaspirin in approximately 1,770 patients presenting with one type ofheart attack called ST-elevated myocardial infarction (STEMI). The aimof this study is to determine whether initiation of Brilinta/Brilique asearly as possible can lead to improved outcomes for these patients.DiabetesType 2 diabetes is a chronic progressive disease and patients oftenrequire multiple medications to control their condition. The diseasecontinues to grow as a consequence of western lifestyles and itincreasingly affects people at a younger age. There are a number ofestablished oral generic and branded classes, such as biguanides andsulfonylureas. However, newer classes such as oral dipeptidyl peptidaseIV (DPP-IV) inhibitors are successfully entering the market by offeringeffective blood sugar control and improved tolerability. Several newclasses of drugs are in development in this area, including sodiumglucosecotransporter-2 inhibitors (SGLT2). CV safety has been givenparticular emphasis in recent regulatory reviews and guidancedocuments provided by the FDA and other regulatory authorities.Our focusOur key marketed productsAstraZeneca continues its strong worldwide 1 collaboration withBMS to develop and commercialise two compounds discovered byBMS (Onglyza (saxagliptin) and dapagliflozin) for the treatment ofType 2 diabetes.Onglyza has been submitted for regulatory review in more than 90countries and approved in 68, including the US, Canada, Mexico, 30European countries, India, Brazil and China. In March 2011, Onglyzabecame the first DPP-IV inhibitor available for use in Europe in Type 2diabetes patients with moderate or severe renal impairment. Thisfollowed the European Commission’s approval of a label update forOnglyza in the treatment of adults with Type 2 diabetes who havemoderate or severe renal impairment. The approved dosage for thispatient group is a once-daily 2.5mg dose.In November, AstraZeneca and BMS were granted approval fromthe European Commission for the marketing authorisation forKomboglyze (a fixed dose combination of Onglyza and metforminimmediate release tablets) as a treatment for adults with Type 2diabetes. The decision applies to the 27 member states of the EU.This followed FDA approval in November 2010 for Kombiglyze XR,a fixed dose combination of Onglyza plus metformin hydrochlorideextended-release tablets. Kombiglyze XR is the first and onlyonce-a-day metformin extended release plus DPP-IV inhibitorcombination tablet providing strong comprehensive glycaemic controlacross glycosylated haemoglobin levels (HbA1c), fasting plasmaglucose and post-prandial glucose. Kombiglyze XR was launchedin January 2011 in the US.1The collaboration for saxagliptin excludes Japan.60 Therapy Area Review CardiovascularAstraZeneca Annual Report and Form 20-F Information 2011