Astrazeneca Plc · LSE:AZN
Astrazeneca — Investor Presentation (2002)
41 slides from Astrazeneca's investor presentation, 2002
Slide 1: Cardiovascular Product Update
Cardiovascular Product Update A Hamish Cameron Vice President and Head of Cardiovascular Therapy Area Key events b Anti-hypertensives beyond pressure reduction b ARBs in heart failure b New anti-hypertensive classes b Progress with statins b New products in thrombosis b New approaches to chronic car
Slide 2: Cardiovascular Therapy Area Mission and Growth Segments
Cardiovascular Therapy Area Mission To increase lifespan and improve the quality of life by reducing the risk, prevalence and impact of cardiovascular disease A CV growth from key disease segments Near-Term Mid-Term Long-term Type 2 diabetes/ Combinations/ AZ242 Metabolic syndrome New approaches Thr
Slide 3: Toprol-XL/Seloken and Atacand lifecycle programme
b Market growth 13% b Toprol-XL® /Seloken® growth 17% YTD b Toprol-XL® /Seloken® sales $820m 3Q 02 MAT b Progress with CHF approvals b HCTZ combination development for US A Atacand® lifecycle programme Study on Cognition and Prognosis in the Elderly CLAIM Studies comparing Atacand to losartan Candes
Slide 4: Atacand – A growth driver
Atacand® – A growth driver b Plain/ Combo Market growth 36% b Growth Atacand® family 41% YTD b Sales $538m 3Q 02 MAT b SCOPE results b Recent FDA CRAC – achievement of superiority labelling vs losartan b CHARM study reports 2003 b DIRECT study recruiting A The benefits of a broad portfolio Of all hy
Slide 5: 'Diabesity' is reaching epidemic proportions
‘Diabesity’ is reaching epidemic proportions A Obesity – Living dangerously Too many calories and too little exercise are the key risk factors for type-2 diabetes. Some 90 percent of people with type-2 diabetes are overweight. Proportion obese % 1991 1998 Newsweek, September 4, 2000 A Cardiovascular
Slide 6: Diabetes – Paying a high price
The Daily Mail A Diabetes – Paying a high price During the ´90s, the prevalence of type-2 diabetes increased by 3% overall, and by 70% among people in their 30s. Diabetes now affects 16 million Americans. Proportion diabetic % 1991 1998 Newsweek, September 4, 2000 A Cardiovascular Product Update: Ha
Slide 7: Diabetes diagnosis and cardiovascular risk guidelines
NCEP/ATP III Guidelines May 2001 Diagnosis of Diabetes = 1 Heart Attack In ATP III Diabetes is regarded as a CHD risk equivalent which puts diabetic patients into highest risk category with LDL goal <100mg/dl A ADA and ACC Cardiovascular Disease Initiative Diabetes Control = Glucose Lipid Blood Pres
Slide 8: Type II diabetes market
Type II diabetes market b Oral hypoglycaemics $8bn b Growth 17% b Avandia® and Actos® A Avandia® and Actos® Growing strongly in the USA Monthly TRx’x (000s) Total TZD - PPAR class $2.3bn sales, 45% growth 1.6 ~16 million scripts 1.4 1.2 1.0 AVANDIA $1.1bn sales, 37% growth 0.8 0.6 ACTOS 0.4 $1.2bn s
Slide 9: PPAR agonist Outcomes Trials
PPAR agonist Outcomes Trials Report dates 2002 03 04 05 06 07 08 2009 Impaired Glucose tolerance DREAM (6000) DREAM Progression to Progression to Diabetes Diabetes 3 year point Follow-up Avandia®/Actos® ACCORD ACCORD Studies (10,000) CV events Type 2 Diabetes CV events 8 year point 4 year point ADOP
Slide 10: GALIDA – dual PPAR alpha/gamma agonist
TM GALIDA A novel, balanced dual PPAR alpha/gamma agonist GALIDA is a trademark of the AstraZeneca group A Galida™ profile b Orally active b Desirable pharmacokinetic/ dynamic profile b Well absorbed b High protein binding b Minimal metabolism b Renal excretion b No effect of food b No CYP450 enzyme
Slide 11: Galida in vitro and triglyceride data
In vitro reporter gene assay mPPARg hPPARa pioglitazone DRF-2725 GalidaTM Activation % Activation % Activation % 100 80 60 50% 40 20 0 0.1 1 10 µM 0.1 1 10 µM 0.1 1 10 µM AstraZeneca: data on file A Galida™ Significant dose-dependent reduction in postprandial triglycerides 0.1mg 0.25mg 0.5mg 1mg -12
Slide 12: Target lipid effects and opportunities beyond PPARs
Target lipid effects PPAR γ GalidaTM target 20% 20% HDL 6 to 13% 10% 0 -10% -5 to -26% Triglycerides -20% -30% -40% -40% A Opportunities in diabetes beyond PPARs Greater efficacy Positive impact New opportunities on co- co-morbidities in development Pipeline of from 2003 pre--clinical pre l entia op
Slide 13: AZD6140 – oral ADP receptor antagonist
AZD6140 an oral ADP receptor antagonist A TRx for Plavix® in the US '000 TRx 1000 900 R2 = 0.95 CURE results published at ACC 800 R2 = 0.99 700 Plavix® Plavix® 600 2mths 500 400 J 00 M M J S N J 01 M M J S Source: IMS Health, NPA Plus A Cardiovascular Product Update: Hamish Cameron 13
Slide 14: AZD6140 profile
AZD6140 profile b Orally active b Non-prodrug b Reversible receptor binding b Rapid onset (no need for loading dose) b More consistent and complete PAI than Plavix® A AZD6140 Oral ADP Receptor Antagonist active at the P2Y12 Receptor Inhibition of platelet aggregation % 4 hours after a 300mg loading
Slide 15: AZD7009 – Atrial Depolarisation Delaying Agent
AZD7009 Atrial Depolarisation Delaying Agent (ARDA) A Effects of intravenous AZD7009 and azimilide on AERP and QT Interval Absolute change ms 200 AERP 150 100 AZD7009 0.09mg/kg/min QT 50 azimilide AERP 0.25mg/kg/min 0 QT -50 0 20 40 60 80 100 120 Time of infusion minutes AstraZeneca data on file S1=
Slide 16: A A Cardiovascular Product Update: Hamish Cameron
A A Cardiovascular Product Update: Hamish Cameron 16
Slide 17: A A Cardiovascular Product Update: Hamish Cameron
Amplitude mV Period time min Internal beat time ms A A Cardiovascular Product Update: Hamish Cameron 17
Slide 18: Anti-thrombotic market development
A Anti-thrombotic market development $bn 25 20 Anticoagulants 15 Antiplatelets 10 5 0 95 97 99 01 03 05 07 09 11 13 15 Source: IMS Health MIDAS, 31 countries MAT Q4/2001. CER and own forecasts A Cardiovascular Product Update: Hamish Cameron 18
Slide 19: Exanta's anticoagulant profile
A Exanta™’s anticoagulant profile wide therapeutic window Safe Therapeutic Range Thrombosis Bleeding Dose, Concentration, or Intensity of Anticoagulation A Cardiovascular Product Update: Hamish Cameron 19
Slide 20: Prevalence of permanent atrial fibrillation rises with age
Prevalence of permanent atrial fibrillation rises with age 12 % of population with permanent atrial fibrillation 10 8 6 4 2 0 20 30 40 50 60 70 80 90 Age Wheeldon, Eur Heart J, 1995 A Stroke: A life threatening and debilitating disease Functional impact of AF-related strokes Uncharacterized 2% 11% T
Slide 21: The burden of warfarin
The burden of warfarin b Coagulation monitoring requirement ✦ use of the International Normalised Ratio (INR) b Commonest cause of acute hospital admission for severe bleeding b Commonest cause of bleeding as adverse events b Accounts for 8% of all cerebral bleeds b Most patients with AF taking drug
Slide 22: Warfarin use in atrial fibrillation; Exanta trial programme
Warfarin use in atrial fibrillation Lower use despite higher risks in elderly patients Source: Wolf. Arch Intern Med. 1987;147:1561.; White. Am J Med. 1999;106:165. A Exanta™ clinical trial programme b Prevention of stroke in atrial b VTE treatment and secondary fibrillation (AF): prevention: 7,700+
Slide 23: SPORTIF II/IV data and Exanta regulatory filings
SPORTIF II/IV 2 year follow up data Centrally adjudicated endpoints Percentage figures normalised for treatment duration Exanta™ warfarin 36mg bd Treatment Years 231 76 Stroke 2 (0.9%)* 2 (2.6%)** TIA 1 (0.4%) 2 (2.6%) Major Bleeds 2 (0.9%) 2 (2.6%) * ischaemic, ** 2 haemorrhagic, non fatal both fat
Slide 24: THRIVE studies – VTE treatment
THRIVE studies – VTE treatment THRIVE III b 1200 patients with previous clinical VTE b Treated with standard of care for 6 months before randomisation b Double blind 24mg b.d. Exanta™ vs placebo b Patients followed for ~18 months and prevention of recurrent VTE determined A THRIVE III – Secondary pr
Slide 25: Individual patient liver profile
A Individual patient liver profile Alanine aminotransferase Multiples of upper limit of normal 10 8 6 4 2 0 0 90 180 270 360 450 540 Days A Cardiovascular Product Update: Hamish Cameron 25
Slide 26: The Exanta clinical trial database
The Exanta™ clinical trial database b Prevention of stroke in atrial b VTE treatment and secondary fibrillation (AF): prevention: 7,700+ patients 3,700+ patients b Prevention of VTE in orthopaedic surgery: b Secondary prevention post-MI: 13,000+ patients 1,900+ patients MAA July 2002 Phase II A A Ca
Slide 27: EXPRESS: study design and results
EXPRESS: study design enoxaparin 40mg sc od Exanta™ sc “knife-to-skin” Exanta™ po 2mg 3mg sc 24mg bid follow-up at operation week 4-6 postop Time -12h 0 12h 24h day 8 -11 venography n=2764 A EXPRESS Trial Exanta™ reduces the risk of proximal DVT plus PE compared with standard prophylaxis with enoxap
Slide 28: Exanta in orthopaedic surgery
Exanta™ in orthopaedic surgery MAA results overview % Total VTE % Major / Severe Bleeding 35 35 30 30 25 25 20 20 15 15 10 10 5 5 0 0 METHRO II METHRO III EXPRESS METHRO II METHRO III EXPRESS Exanta™ 24mg bd comparator A Orthopaedic surgery VTE prophylaxis Differences in clinical practice North Amer
Slide 29: EXULT A and EXULT B
EXULT A Exanta™ vs warfarin in orthopaedic surgery warfarin (INR 2.5) Exanta™ 24mg bid Exanta™ 36mg bid 27.6% 24.9% 20.3% 0.8% 1.3% 0.8% Total VTE Major bleeds warfarin vs. Exanta™ 36mg p = NS p = 0.003 TKR n=1700 A EXULT B Study design (Post-op start) Total knee replacement warfarin (INR 2-3) R Exa
Slide 30: A A Cardiovascular Product Update: Hamish Cameron
A TM A Cardiovascular Product Update: Hamish Cameron 30
Slide 31: The statin market
The statin market b Today worth $18 billion b 2001 growth +17%, despite cerivastatin withdrawal b 2005 market forecast $20-$25 billion b Continued growth driven by ✦ increasing prevalence ✦ only half of eligible patients treated ✦ poor control despite treatment ✦ increasingly aggressive guideline ta
Slide 32: New guidelines expand number of possible patients for treatment
New guidelines expand number of possible patients for treatment especially for those with CHD or CHD risk equivalent Millions of patients 20 15 ATP II ATP III 10 5 0 CHD or 2+ risk factors <2 risk factors equivalent ATP III LDL Goal< 100 mg/dL < 130 mg/dL < 160 mg/dL Third Report of the Expert Panel
Slide 33: Crestor versus atorvastatin
Crestor™ versus atorvastatin Greater LDL-C reduction 5 10 20 40 80 Dose mg 0 -10 -20 -30 atorvastatin Crestor™ n=166 n=209 -40 -50 Difference in % reduction -60 across the dose-range: 8.42%; p<0.001 -70 LS mean Baseline means across study: % change from baseline (SE) 4.8-5.1 mmol/L (185-198 mg/dL) L
Slide 34: Crestor versus atorvastatin; safety profile
Crestor™ versus atorvastatin Greater HDL-C and Apo A-1 elevation HDL-C Apo A-I Mean % change Mean % change from baseline from baseline 14 14 12 12 * 10 10 Crestor™ ** 8 8 ‡ Crestor™ 6 6 4 atorvastatin 4 2 2 atorvastatin 0 0 5 10 20 40 80 5 10 20 40 80 Dose mg Dose mg * p <0.001 vs atorvastatin ‡ p <
Slide 35: Crestor safety profile – Liver, Muscle
Crestor™ safety profile b Liver b Muscle A Statin risk benefit Myopathy or CK> 10X ULN Normalised for LDL reduction Incidence CK source rosuvastatin (10 - 40) 1 2.5 cerivastatin (0.2 - 0.8) 2 pravastatin (40-80) 3 atorvastatin (10-80) 3 2.0 CK with symptoms lovastatin (20-80) 3 1.5 simvastatin (20 -
Slide 36: Crestor safety profile and regulatory status
Crestor™ safety profile b Liver b Muscle b Kidney A Crestor™ regulatory status b RMS and Mutual Recognition procedure b USA b Japan A Cardiovascular Product Update: Hamish Cameron 36
Slide 37: Crestor 10-40mg; research beyond the NDA
Crestor™ 10-40mg b Best in class efficacy profile b More patients to guidelines with 10mg start dose b Safety comparable to other marketed statins A Crestor™ research beyond the NDA Post NDA trials – twice the patients in half the time UK Canada Netherlands Germany France Norway Finland UK Czech Rep
Slide 38: GALAXY CV Risk Reduction Hypothesis
A GALAXY CV Risk Reduction Hypothesis The GALAXY programme is designed to confirm that the statin with: Best effects on the atherogenic lipid profile and positive changes on inflammatory markers Profound benefits on atherosclerosis Best reductions in CV morbidity and mortality A Cardiovascular Produ
Slide 39: Crestor GALAXY research programme
A Crestor™ GALAXY Research programme 2001-2010 Basic science Stellar Effect on lipids Mercury I 10,000s Mercury II patients Effect on Meteor inflammatory Orbital Asteroid markers Discovery Aurora >30 Effect on atherosclerosis Lunar countries Jupiter Celestial Saturn Getting to recommended Comets Cor
Slide 40: Cardiovascular future regulatory filings
TM A Supporting the AstraZeneca transformation Cardiovascular future regulatory filings NCEs Galida™ AZD7009 Diabetes AF - oral Crestor™ Crestor™ 2003 04 05 Atheroma Outcomes Major line Exanta™ Atacand® Atacand® Atacand® Exanta™ extensions / A Fib/ CHF Paeds DIRECT Post-MI new VTE Rx/ indications OS
Slide 41: Cautionary statement regarding forward-looking statements
Cautionary statement regarding forward-looking statements In order to utilise the “Safe Harbor” provisions of the United States Private Securities Litigation Reform Act of 1995, AstraZeneca is providing the following cautionary statement. This presentation contains forward-looking statements with re