Geriatric Rounds: Compounds of Medical Need March 28, Albert Giovenella, Ph.D. Adjunct Asst. Professor of Medicine

Transcription

1 Geriatric Rounds: Compounds of Medical Need March 8, 04 Albert Giovenella, Ph.D. Adjunct Asst. Professor of Medicine

2 My Background at Penn (Disclosure Slide) Mycobacterial Laboratory Supervisor (H.U.P.) Ph.D. Studies Instructor of self-written course (Grad. Sch. of Education) 994- Instructor, School of Dental Medicine Adjunct Asst. Prof. (Geriatrics Risa Mourey) 007- Pres Adjunct Asst. Prof. (Geriatrics Jerry Johnson) Other: Army National Guard Grad. Teaching Asst for Master s Degree West Chester University Smithkline Beecham Merck & Co. 996 Founder Of PA Osteoporosis Society

3 30 Complete Total of NMEs (U.S. Approved) Only (Rolling Total By 0-year segments) NMEs Best straight line (93 at beginning of 04) The Biotech Effect Copyright: A. Giovenella, Source: Drugs/FDA Website as of March 8, 04

4 Pre-Approval Drug Development Strategy Grid Approval Window (DiMasi Window) Average Approval Time 8- years Post-Approval $ X $800 mil-----$. bill. Average R&D Investment 0 0 Copyright: A. Giovenella, 009 Exclusivity Data from DiMasi, Tufts, Sep 009; Approval Window Data from Tufts, 007

5 Generic Presence in 008 Prescriptions 0% Branded 37% Generic 63% Source: IMS Data as of February, 008

6 Generic Presence in 03 Prescriptions 0% Branded 6% Generic 84% Source: Kaiser Health News as of May 9, 0 Copyright: A. Giovenella, 009

7 Evolved Alternative Pathway for the Drug Discovery Process Traditional Drug Research Pathway for Pharma LC (Pharma) Laboratory Discovery (In-vitro) Pre-Clinical Research Phase I Phase II Phase III NDA II a II b Increasing Risk to Adverse (Unmanageable) Levels Optimal Range of Compound Acquisition SC (Biotech) Laboratory Discovery (In-vitro) Pre-Clinical Research Biotech Phase I Phase II Phase III Phase III or Post-Approval (Drug Acquisition or Licensing Acquisition Drug Research Pathway Copyright: A. Giovenella, 00 Looking for Exit Strategy Managing Risk or Company Acquisition)

8 FDA CDER & CBER Breakthrough Therapy Designations In the FDA SIA (Safety and Innovation Act) of 0, in Section 90, the FDA allowed for BREAKTHROUGH THERAPY DESIGNATIONS in order to expedite development and review of drugs for life-threatening and serious diseases. In order for the sponsor to receive this designation for a drug in development, the sponsor must show: ) Evidence that the drug is intended, alone or in combination with one or more other drugs, to treat a serious or life-threatening disease or condition, and ) Preliminary clinical evidence indicating that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development. Source:

9 FDA CDER & CBER Breakthrough Therapy Designations (As of March, 04) Small Molecules Biologics Vacc GSK Novartis Roche Pharmacy Vertex USA Other Countries 9 4 4() () Phase I Phase II Phase III NDA Sub Appr Kinase Inh Polym/Prot B Cell Targets CFTR Mkt Cap ($) Therap Area Disease State Approved: >00 BN <00 MIL PRIV 3 Oncology 4 Anti-infective 8 Respiratory 3 Metabolism 3 Muscle Neurology Cardiology Dermatology Hematology Cancer 4 Hepatitis C 4 Cyst Fibrosis 3 Year Therap Area Company 03 Oncology Pharmacyclics / J&J Oncology Roche (Genentech) Anti-infective Gilead 04 Oncology Pharmacyclics / J&J Respiratory Vertex Copyright: A. Giovenella, 03 FDA Breakthrough Therapy Web Page, March 8, 04

10 Other Diseases Targeted by Breakthrough Therapy Drugs Hepatitis C (3 entries) Cystic Fibrosis ( entries) Duchenne Muscular Dystrophy Malaria (Plasmodium vivax) Bleeding Disorder from Factor Xa inhibitors Molybdenum Cofactor Deficiency Type A Sporadic Inclusion Body Myositis Lysosomal Acid Lipase Deficiency (Wolman Dis) Epidermolysis Bullosa Lambert-Eaton Myasthenic Syndrome Bacterial Meningitis Type B

11 TOTAL = Breakthrough Designations by Therapeutic Area in U.S. Since N = 3 4 Oncology (4 B) 8 Antiinfective 3 Metabolism 3 Respiratory Muscle ( B) Neurology Cardiology Dermatology Hematology 0 GI 0 Anti-inflammatory 0 OB-GYN 0 Anesthesiology 0 Analgesic 0 Bone BIOLOGICS (inc) (Jan-Mar) Oncology Neurology Anti-infective Cardiology Hematology Metabolism Muscle Respiratory BIOLOGICS Dermatology Copyright: A. Giovenella, Source: FDA Database, PharmaLive, Evaluate Pharma & A. Giovenella March 8, 04

12 TOTAL = Breakthrough Designations by Therapeutic Area in U.S. Since Resp-4 () AI-3 () N = 3 3 Onc-3 (): Onc-4 () AI-3 Resp-4 () 4 Oncology (4 B) 6 Antiinfective 3 Metabolism 3 Respiratory Muscle ( B) Neurology Cardiology Dermatology Hematology 0 GI 0 Anti-inflammatory 0 OB-GYN 0 Anesthesiology 0 Analgesic 0 Bone BIOLOGICS (inc) 0 6 Onc-3 () Onc-4 () A 04A (Jan-Mar) (Jan-Mar) Oncology Neurology Anti-infective Cardiology Hematology Metabolism Muscle Respiratory BIOLOGICS Dermatology Copyright: A. Giovenella, Source: FDA Database, PharmaLive, Evaluate Pharma & A. Giovenella March 8, 04

13 Time from Designation to Approval Since 03 N = 03: 4 mo Hepatitis C $ 9.3 B MC (Ph III) A-I (Gild) 6 mo Chron Lym Leuk $ 7.7 B MC (Ph III) Onc (Roch) 7 mo Mantle Cell Lymph $ 63./$9 B MC (Ph III) Onc (Ph/J&J) 04: 0 mo Chron Lym Leuk $ 60.4 B/ $0. B (Ph III) Onc (Ph/J&J) 3 mo Cyst Fibro (8 mut) $ 0.0 B (Ph III) Resp (Vtx) TOTAL APPR = (Jan-Mar) Hep C CLL Mtl Cell Lym Cyst Fib Copyright: A. Giovenella, Source: FDA Database, PharmaLive, Evaluate Pharma & A. Giovenella March 8, 04

14 TOTAL = Breakthrough Designations by Market Cap in U.S. Since N = 3 > 0 B B -00 B B B -7 B B - B 3-0 B M M 0-00 M M 00 M or less 3 PRIV (Jan-Mar) >0 B 0-0 B -00 B 0-0 B B -7 B 6-0 B - B -0 B M 0-70 M -00 M 0-0 M 00 M or less PRIV Copyright: A. Giovenella, Source: FDA Database, PharmaLive, Evaluate Pharma & A. Giovenella March 8, 04

15 TOTAL = Breakthrough Designations by Oncology (Types of Cancer) in U.S. Since MCL-3 CLL-3 CLL-4 N = 6 3 NSCLC 3 CLL Breast MM AML Melanoma NHL Mantle Cell Lym Waldenst Macrog SLL Non-spec 0 Prostate 0 Liver 0 Pancreatic 0 Brain 0 MCL-3 CLL A 04A (Jan-Mar) (Jan-Mar) NSCLC NHL CLL AML Breast Mult Myel Melanoma SLL Waldenst Macrog Mantle Cell Lym Non-spec CLL-3 Copyright: A. Giovenella, Source: FDA Database, PharmaLive, Evaluate Pharma & A. Giovenella March 8, 04

16 Summary As biomedical research continues, the FDA has made the Breakthrough Therapy Designation (BTD) to expedite development & approval in areas of medical need. Approval times for first BTD approvals range from 4 months to 3 months since receiving the designation. Oncology research is the dominant therapeutic area receiving BTD thus far. In this oncology research, the most BDT designations---- and approvals are for chronic lymphocytic leukemia.