New Global Trends in Novel

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1 New Global Trends in Novel Oncology Drug Development Harish Dave, MD, MBA Vice President Medical and Scientific Services Quintiles September 18, 2010

2 Oncology Market Attractiveness Opportunity exists in lower prevalence tumors where unmet need is high and in higher prevalence tumors for specific sub populations Unmet Need: 5-year Surv vival Rates Market Attractiveness Landscape for Major Tumors Pancreatic 0% Multiple Myeloma 20% 40% 60% 80% 100% Higher Unmet Need / Lower Prevalence Lung Ovarian Renal AML CML Lower Unmet Need / Lower Prevalence Thyroid 4 Breast and prostate are the highest prevalence tumors but have low unmet needs except for specific subpopulations Colorectal Higher Unmet Need / Higher Prevalence Size of bubble: R&D Competitive Intensity Fewer drugs in clinical development More drugs in clinical development Lower Unmet Need / Higher Prevalence Increasing fragmentation of patient populations Prostate Breast Key Takeaways 4 Competitive intensity is relatively high 4 Lung cancer is an attractive market but competitive intensity is high 4 Market opportunity exists in lower prevalence tumors that tend to be less well characterized genomically 4 Potential orphan drug populations ,000 1,500 2,000 2,500 3,000 Projected Prevalence By Tumor Type (2017 / in 000 s) 2 Note: Bubble size represents number of drugs in development Phase I-III Source: ADIS, SEER, Decision Resources, Quintiles Analysis

3 Global Pharmaceutical Market Global Market $600 billion % 1995 (200) 1997 (220) 1999 (260) 2003 (466) 2004 (518) 2006 (600) USA 31% 35% 41% 52% 54% 52% 22% 52% Japan 21% 16% 13% 12% 11% 9% Europe 29% 29% 30% 23% 23% 22% 9% Others 19% 20% 16% 12% 12% 17% USA Europe Japan Others 3

4 Global Market Analysis Global cancer market sales $56B in 2007 Top 10 leading brands = 45% of sales Antineoplastics and immunostimulants arelargest categories Main growth anticipated in targeted therapies and biologics Overall market size forecast to reach $77B in

5 Oncology Pipeline WHO is predicting a 50% increase in global cancer incidence in Oncology accounts for ~25 30% of the estimated $336bn R&D budget 725 oncology agents in active clinical development 2 Bladder cancer Brain cancer Breast cancer Cervical cancer Colorectal cancer Head/neck cancer Kidney cancer Leukemia Liver cancer Lung cancer Lymphoma Multiple myeloma Ovarian cancer Pancreatic cancer Prostate cancer Sarcoma Skin cancer Solid tumors Stomach cancer Cancer-related conditions Other cancers Unspecified cancers Medicines in development for cancer* Should we be optimistic? 203 *Some medicines i are listed in more than one category 1. The WHO Media Centre. (accessed 26 April 2010). 2. PhRMA Report Medicines in development for cancer. (accessed 19 March 2010). 5

6 Oncology Development Activity 73 specific indications mapped to 34 therapeutic areas 1 in 5 programmes does not have a specific tumour target identified flagged as targeting solid tumours or cancer, general Lung, breast, colorectal and prostate cancer remain leading development targets A number of haematological cancers have strong phase I pipelines 6

7 Oncology Development Activity 123 different mechanisms identified reflecting the high R&D focus being applied to oncology Excludes compounds with unidentified pharmacology 7

8 R&D productivity has dropped significantly FDA NME approvals 1 (number) Lagging 5 year ave Industry R&D spend $ Billions Number of NME approvals 1 Lagging 5 year average, includes NCEs and BLAs. BLAs included 1986 onward; biologics approvals in prior years assumed negligible SOURCE: NME data for from Peltzman, S. (1973) J. of Political Economy 81, no. 5: NME data for as reported in Hutt, P.B. (1982) Health Affairs 1(2) NME Data for from Parexel s Pharma R&D Statistical Sourcebook 2009/2010, FDA, and PhRMA. Industry R&D spend data from PhRMA Annual Membership Survey, 2008 and Parexel 2009/2010 8

9 Intensifying Competitive Dynamics The dominant competitive dynamic is the burgeoning industry-wide cancer drug pipeline with an increased strategic focus on oncology 4 FDA focus on safety 4 Impact on payer oncology budgets 4 Regulatory pathway for biosimilars Emerging Generic Market for Oncology Robust Oncology Pipeline Drives Greater Competition Small, but increasing impact in 5-10 years Corporate Strategic Focus on Oncology to Drive Di Profit 4 10 companies with 75% of oncology sales 4 ~2,000 molecules in development 4 1,000 in clinical trials 4 ~250 new anti-cancer molecules/ indications Large impact in 5-10 years 4 Blockbuster expirations 4 M&A, collaboration, licensing to enter cancer market quickly 4 Fewer company disease/technology bets Moderate impact in 5-10 years 9

10 Evidence of Pharma s Therapeutic Refocusing Activity is Publicly Visible Publicly Visible Sanofi has reviewed its research programs and made cuts to internal R&D and increased small- to mid-sized biotech acquisitions Pfizer to focus on areas such as oncology, diabetes & regenerative medicine. Abandoning several areas including heart disease, osteoarthritis and anaemia Roche has aligned its R&D into five disease biology areas: Oncology, Virology, Inflammation, Metabolism and CNS Wyeth is reducing its therapeutic portfolio from 14 to 6 fields, including cancer, vaccines and metabolic disease, and from 55 to 27 diseases Faced with AZ streamlined its R&D increasing R&D model to focus on costs, poor ROI and GSK subdivided id d research Neuroscience, Cancer, declining revenues operations into small 'drug Respiratory & Inflammation, large pharma are performance units' and cut Cardiovascular, restructuring R&D 1,200 R&D jobs Gastrointestinal and Infection and focusing on fewer indications Source: Company Press Reports 10

11 The Brutal Facts High Attrition Makes Drug Development a Risky Business Market Launch 15 FDA Review Phase III Clinical Trials 1 2 Post-Marketing Surveillance Pivotal Efficacy & Safety 10 Phase II Clinical Trials 2-5 POC, Dose Response Phase I Clinical Trials 5 10 Safety/Tolerance PK 5 Preclinical Testing DMPK,Safety Chemistry 0 Years Basic Research 3,000 10,000 Number of Compounds Source: PhRMA analysis of Tufts CSDD database Screening Synthesis 11

12 Is oncology more productive than other therapy areas? Success rates from first-in-man to registration 20 Percentage e of success % Arthritis and pain Ophthalmology Cardiovascular CNS Infectious disease Oncology Metabolic disease Urology Women s health All The data are from the ten biggest drug companies during (the companies are AstraZeneca, Bristol- Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, GlaxoWellcome, Johnson & Johnson, Novartis, Pfizer, Pharmacia, Schering-Plough and SmithKline Beecham; data were obtained by Datamonitor in the Pharmaceutical Benchmarking Study). CNS, central nervous system. Oncology success rate = 5% versus 11% DiMasi JA, Grabowski HG. J Clin Oncol 2007; 25:

13 Drug Development Risks Market segmentation Disease Biomarkers omics Pricing Risk Price cuts imposed by payors Not happened yet in developed markets but significant risk remains Restriction at national level Pharmacoeconomic issues Price erosion Failureofcandidate agents False positive signals with late phase failure But what about false negative signals? 13

14 Reasons for Poor Productivity Easy discovery is over Greater demands from regulators Public expectations about safety and efficacy Poor recruitment is clinical studies Rising development costs Market segmentation Role of new technologies 14

15 Optimizing drug development Biomarker driven strategies Targeted therapy = defined disease segment Early go-no go decision Focus resources on success Adpative trial designs Operational efficiencies Virtual drug develop ment teams 15

16 Phase I designs Novel/rapid phase I dose escalation From cytotoxic to cytostatic mechanisms Revision of response criteria to view stable disease as a clinical benefit Goal: define optimal dose and schedule (Vaccines??) Low toxicity: no need for MTD (max tolerated dose) Specific activity: OBAD = Optimal Biological Active Dose (or max target inhibition dose) better than MTD? But how to measure OBAD?? Biopsies and phosphorylation Imaging technologies (PET scans) Biomarkers Early phase I combination studies with chemotherapy ( Octopus trials) Applicable to Healthy Volunteers? ou tees 16

17 Role of Phase II Estimate clinical activity Further characterize safety/toxicity Understand dbiology of disease and MoA of drug Additional opportunity to make go no go decision 17

18 Unresolved Phase II issues Will biomarker strategy suffice Are these sufficiently validated Which patient population Discontinuation studies? What line of therapy Are we waiting too long? Combination approaches With classical chemotherapy Novel:novel 18

19 All patients? Which Patients? Ethical andfinancial considerations Only Patients who express the marker? (e.g., Her 2 +++) Not true for Erb1 targeting drugs (Erbitux) Reliability / evolution of technology Statistical issues around sample size Retrospective analyses not accepted by Regulators Stage of disease: early vs metastatic Treatment duration Stop at PD or continue? Continue or stop at CR? 19

20 Which Indications? The big ones will remain the big ones Breast, Lung, Colorectal, Prostate With targeted therapies improved outcomes in less frequent diseases Pancreas (e.g Tarceva) RenalCellCancer (e.g Sunitinib, mtor inhibitor) Head and Neck (e.g Erbitux) NHL (Rituximab) And it will happen to others Melanoma and vaccines Ovarian cancer Thyroid cancers.. 20

21 Regulatory Challenges Harmonisation USA EUR Japan None consider the same endpoints! Long delays in Europe, excessive bureaucracy Gene therapy: 9 mo average between 1st filing and FPI 50 pts trial, Ph II, 8 sites, 20 committees, 300+ experts to give an opinion! Endpoints in oncology trials il Will have to change with targeted therapies Cancer to become a chronic disease New statistical methodologies Adaptive trial designs 21

22 Moving forward... Oncology drug development must: become more productive become cost efficient identify effective agents, appropriate biomarkers, and target populations Ultimate aim is to improve patient outcomes 22