AstraZeneca PLC · LSE:AZN
AstraZeneca — Technical Presentation (2000)
37 slides from AstraZeneca's technical presentation, 2000
Slide 1: Cardiovascular Therapy Area review
A Cardiovascular Therapy Area review Dr Hamish Cameron Vice President, Head of CV Therapy Area Causes of death Infectious and Chronic obstructive parasitic diseases lung diseases Other and Injury and poisoning unknown causes Maternal and perinatal causes Cancer Cardiovascular diseases A Hamish Camer
Slide 2: Cardiovascular summary - 2000
A Cardiovascular summary - 2000 Customer patient/consumer/payor/purchaser Dyslipidaemia Obesity Type II DM / IRS Acute coronary Hypertension syndromes Symptomatic angina pectoris Venous Discovery thromboembolism Heart failure Development & & Licensing Arterial Vascular disease Commercial- embolism p
Slide 3: Building the future using a disease area focus
Building the future using a disease area focus Type II diabetes Hypertension Venous Venous thrombo - Obesity thrombo - embolism (OD Dyslipidaemia embolism anticoagulant) Arrhythmia (1st ODTI) Vascular Arterial embolism disease Heart failure (OD anticoagulant antiplatelet) prevention Near-term Mid-te
Slide 4: Atacand
A Atacand® b Growth 98% b 3Q MAT sales of $213m b Data differentiation from other ARBs b Growing market share A Hamish Cameron & Ian Watts - CV Page 4
Slide 5: Atacand – challenging the market leader
Atacand® – challenging the market leader Market Share 70% Atacand® MAT Q1/99 60% Atacand® MAT Q1/00 50% Cozaar® MAT Q1/99 40% Cozaar® MAT Q1/00 30% 20% 10% 0% USA Germany France* Italy Spain* UK * Retail pharmacy sales only Source: IMS MIDAS Q1 2000 Exchange rate used: Actual A Atacand® - fastest gr
Slide 6: Atacand – class leading life cycle-development
Atacand® – class leading life cycle-development Study on Cognition and Prognosis in the Elderly CLAIM Studies comparing candesartan to losartan Candesartan in Heart Diabetes Retinopathy failure Assessment of Reduction Candesartan Trial in Mortality and Morbidity A The CLAIM studies - Atacand® superi
Slide 7: Atacand Plus vs Hyzaar; the SCOPE trial
Atacand® Plus/HCT compared with Hyzaar® in moderate-severe hypertension Systolic Diastolic 24 hours 48 hours 24 hours 48 hours 0 0 -10 -10 -20 -20 p<0.001 -30 p<0.001 -30 p<0.001 -40 -40 ∆DBP p<0.001 mm Hg ∆SBP mm Hg Means, 95% CI Atacand® Plus 16/12.5 mg (n=81) Hyzaar® 50/12.5 mg (n=79) Ref: König
Slide 8: Questions about ARBs in CHF; CHARM programme
Questions about ARBs in CHF b Can ARBs beat placebo? CHARM b Can ARBs be better than ACE-I? ELITE-2 b Can ARBs and ACE-I in combination CHARM be better than ACE-I alone? ValHeFT b Can ARBs provide benefit in CHF with preserved LVEF? CHARM A The CHARM study programme b 7500 patients b Patients alread
Slide 9: Worldwide prevalence of diabetes mellitus
A Worldwide prevalence of diabetes mellitus 300 - Number of cases (millions) 250 - 200 - 150 - 100 - 50 - 0- 1995 2000 2005 2010 Source: WHO A Hamish Cameron & Ian Watts - CV Page 9
Slide 10: Diabetic eye disease
Concerns in the mind of newly diagnosed diabetics % of subjects 40 - 30 - 20 - 10 - 0- Long-term Hypo- Kidney Amputation Eye Heart Impotence Concerns Decreased poor health glycaemia disease disease disease about life pregnancy expectancy Reproduced with permission from Dunning Pl. The diabetes Educa
Slide 11: Diabetic Retinopathy; the DIRECT study
Diabetic Retinopathy b Rare in first few years of type 1 diabetes b Present in 20% of type 2 diabetics at diagnosis b Affects over 70% of all diabetics A The DIRECT study b 4500 patients b 200 centres b 20 countries b Type 1 with and without retinopathy b Type 2 already with retinopathy b Randomised
Slide 12: Atacand – life-cycle management
Atacand® – life-cycle management CLAIM 99 00 01 02 03 04 05 06 A A Cardiovascular Therapy Area review Dr Ian Watts Global Product Director, CV Therapeutic Area Hamish Cameron & Ian Watts - CV Page 12
Slide 13: Arterial/venous thrombosis
Arterial/venous thrombosis Ischaemic Stroke b venous Coronary artery thromboembolism thrombosis from atrial fibrillation b plaque rupture b plaque rupture – arterial thrombosis – unstable – TIA/Stroke angina – myocardial Pulmonary infarction embolism Deep vein thrombosis A A growing market based on
Slide 14: H376/95 Oral Direct Thrombin Inhibitor
H376/95 Oral Direct Thrombin Inhibitor Our goal: replace warfarin in its approved indications and expand the use of anticoagulation A Product profile of H376/95 – the ‘ideal’ oral anticoagulant warfarin H376/95 Effective anticoagulant ! ! Direct and reversible mechanism of action x ! Rapid onset/off
Slide 15: H376/95 development strategy – chronic indications
H376/95 Oral Direct Thrombin Inhibitor b Oral anticoagulation made safe, simple and convenient b Equal or better efficacy than warfarin b A new standard of care in oral anticoagulation A Development strategy H376/95 – chronic indications b Treatment of VTE - status: phase III – The first chronic ind
Slide 16: H376/95 short term indication; METHRO II
Development strategy H376/95 - short term indication b Prophylaxis VTE in orthopaedic surgery - status: phase III – Proof of concept indication – Opportunity to demonstrate superior efficacy/product profile to warfarin and LMWHs A METHRO II VTE in all patients VTE (%) Distal DVT 40 p< 0.0001 Proxima
Slide 17: Phase II/III orthopaedic surgery efficacy results with H376/95
Phase II/III orthopaedic surgery efficacy results with H376/95 (24 mg b.d.) 24 mg b.d. H376/95 comparator 35 30 Total VTE-rate (%) 25 20 15 10 5 0 METHRO Study 203 METHRO Study 236 II III A The effect of treatment time on treatment effect 35 No. 203 Total VTE-rate (%) in knees 30 No. 236 Methro III
Slide 18: H376/95 human safety experience and key messages
Summary – human safety experience with H376/95 b Over 5000 patients exposed b Doses H376/95 up to 60 mg bd for 12 weeks administered without significant bleeding concerns b No requirement for urgent reversal anticoagulation b Atrial fibrillation patients treated for 18 months with no coagulation mon
Slide 19: Secondary prevention of CHD events: 4S
Secondary prevention of CHD events in a high-risk CHD population (TC 5.5-8): 4S Total CHD Nonfatal CABG/ mortality mortality MI PTCA 0 –10 % Risk reduction –20 –30 -30% –40 -37% -37% -42% –50 All risk reductions are p<0.05 vs placebo 4S Group: Lancet 1994;344:1383–1389 A The need for better care b N
Slide 20: The rule of thirds
The rule of thirds Total population diagnosed treated with lipid lowering agent successfully treated A Public unaware of cholesterol as CHD risk factor Physicians believe their patients Only half the public is aware (after know cholesterol is associated prompting) that high cholesterol with CVD incr
Slide 21: Lipid market – large and still growing
Lipid market – large and still growing Anti-ulcerants + 13% Cholesterol/Triglyceride + 22% Reducers Anti-depressants + 16% Calcium antagonists + 5% Anti-rheumatic N-steroid + 28% Ace Inhibitors + 4% 0 5,000 10,000 15,000 20,000 US$ millions Source: IMS Health MAT Q1 /2000 major 33 countries A Impres
Slide 22: Crestor – pre-clinical and clinical pharmacology
TM A Crestor™ – ™ pre-clinical and clinical pharmacology b Potent inhibitor of HMG CO-A reductase in vitro and in vivo b Highly selective for hepatocytes b Predictable PK, linear across the dose-range b Reduced likelihood for drug:drug interactions via CP450 3A4 b No PK effect of age/gender b Mild t
Slide 23: Dose-related reductions in LDL-C with Crestor
Dose-related reductions in LDL-C ™ up to 65% with Crestor™ Dose (mg) P 1 2.5 5 10 20 40 80 10 80 Mean percentage change (±SE) 0 -10 -20 from baseline -30 * -40 * * -50 * placebo (P) * -60 CrestorTM * * atorvastatin -70 Baseline means across study: * p<0.001 (CrestorTM vs. placebo) 4.7– 5.1 mmol/l (1
Slide 24: Crestor – comprehensive phase III programme
Crestor™ – ™ comprehensive phase III programme b Over 4000 patients randomised b Programme completes this month b Comparative data available against: – atorvastatin, simvastatin, pravastatin b Efficacy and safety compared to and in combination with: – niacin, fenofibrate, cholestyramine, HRT A Crest
Slide 25: Crestor – comparative endpoint data available
Crestor™ – ™ comparative endpoint data available b LDL-C lowering b Percentage of patients reaching LDL-C goal (NCEP and EAS) b HDL-C and triglyceride effects b Apolipoprotein and lipoprotein effects – Apo B, Apo A-1, Lp (a) b Ratio effects: – LDL-C/HDL-C; non-HDL-C/HDL-C; TC/ HDL-C; Apo B/ Apo A-1
Slide 26: LDL-C reductions with Crestor vs pravastatin and simvastatin
™ LDL-C – significantly greater reductions with Crestor™ than with either pravastatin or simvastatin pravastatin simvastatin CrestorTM CrestorTM 20mg 20mg 5mg 10mg 0 Change from baseline (%) -10 -20 -28 -30 -37 -42 -40 -49 -50 p<0.001 p<0.001 -60 p<0.01 p<0.001 A Percentage of patients achieving ™ N
Slide 27: Patients achieving NCEP LDL-C goal; ACC abstract titles
Percentage of patients achieving ™ NCEP LDL-C goal* 100 High risk category (documented Patients achieving target LDL-C (%) atherosclerosis or diabetes mellitus) 80 60 67 40 42 20 19 7 0 pravastatin simvastatin CrestorTM CrestorTM 20mg 20mg 5mg 10mg *no statistical analysis was performed A ™ Crestor™
Slide 28: Crestor roll-out of phase III results
™ Crestor™ roll-out of phase III results b Abstracts will be submitted to all major Cardiology and Lipidology Congresses in 2001: – ACC, EAS, EASD, DALM, ESC, AHA and others b First results to be presented at the ACC, March 19th - 21st, Orlando, Florida A ™ Crestor™ – the confidence to expand... b P
Slide 29: Crestor outcomes programme – endpoint measurement
Crestor™ outcomes programme - ™ endpoint measurement b All-cause mortality b CV mortality b Events (MI, death, stroke etc) b Arterial wall surrogates (plaque regression) b Biochemical surrogate endpoints (LDL,HDL,TG) A TM A Hamish Cameron & Ian Watts - CV Page 29
Slide 30: AZ242 – development programme
Diabetes as a cardiovascular risk factor - the opportunity for PPAR agonists Microvascular Macrovascular complications complications Retinopathy blindness Heart Myocardial Neuropathy amputation Infarction Nephropathy kidney failure Brain stroke /dialysis CV Death Glycaemic Control Lipids Lipids PPAR
Slide 31: Atrial Fibrillation is a cause of considerable morbidity and mortality
Atrial Fibrillation (AF) is a cause of considerable morbidity and mortality b Doubles the mortality rate (Framingham Heart Study) b 15% of all strokes due to AF b 30% of patients undergoing cardiac surgery develop AF post-operatively A Torsades des Pointes A Hamish Cameron & Ian Watts - CV Page 31
Slide 32: Atrial Fibrillation – strategy
Atrial Fibrillation – strategy b Broad approach via different targets b Atrial Repolarisation Delaying Agents (ARDA) without ventricular proarrhythmic potential (Phase I) b ARDA follow-up compound (pre-development) b Mixed channel approach, in-licensed compound from Nortran (pre-development) A AR-H0
Slide 33: ZD4927 Phase I results; P2T Antagonist AZD6140
ZD4927 Phase I results – plasma Anti-Factor Xa activity over time Anti Factor Xa U/ml 2.5 10 mg/kg ZD4927 (n=6) 5 mg/kg ZD4927 (n=6) 2.0 2.5mg/kg ZD4927 (n=6) 1mg/kg ZD4927 (n=6) 1.5 1.0 0.5 0.0 0 4 8 12 16 20 24 Time (hours) A P2T Antagonist AZD6140 % Inhibition Substantial inhibition of platelet 1
Slide 34: Key brand filing dates to 2005
Genomics in cardiovascular research (AstraZeneca, Mölndal) Expression Human linkage Mouse linkage Candidate profiling and programmes programmes genes proteomics - Procardis - Ath1 and concepts programmes - IRS Validation of disease relevance Population based resources MI cases and controls Swedish T
Slide 35: Phased market entry into key segments
Phased market entry into key segments Type II diabetes Hypertension Venous Venous thrombo - Obesity thrombo - embolism (OD Dyslipidaemia embolism anticoagulant) Arrhythmia (1st ODTI) Vascular Arterial embolism disease Heart failure (OD anticoagulant antiplatelet) prevention Near-term Mid-term Long-t
Slide 36: Genomics
Genomics H376/95 AZ242 PPAR agonist (II) Factor Xa’s (II) • Orthop. surgery (III) Atacand DIRECT (III) New Disease Targets • General surgery (III) New Disease Targets • Treatment of VTE (III) • Atrial fibrillation (III) Type II diabetes Hypertension Venous Venous thrombo Obesity thrombo - -embolism
Slide 37: Phased market entry into key segments
Phased market entry into key segments Plendil® H376/95 AZ242 PPAR agonist (II) Factor Xa’s (II) New Seloken® ZOK • Orthop surgery (III) Atacand DIRECT (III) New Disease Disease Zestril®/Zestoretic® • General surgery (III) New Disease Targets Targets Targets Atacand®/Atacand® Plus • Treatment of VTE