Pharmacogenomics: Implications for CNS Drug Development in the 21st Century

1. Pharmacogenomics: Implications for CNS Drug Development in the 21st Century Challenges for Development & Approval – Patient & Funding Agency Perspective Valerie A. Cwik, M.D. Senior VP – Research & Medical Director MDA

2. Rare diseases

3. Advances in Duchenne muscular dystrophy • Described in 1868 • Gene identified in 1986 • Dystrophin identified 1987 • Nearly all mutations now identified through genetic testing • 2009: gene therapy, stop codon readthrough and exon skipping in human clinical trials • ~15,000 individuals living with Duchenne/Becker MD in the US • Fewer than 250 currently participating in human clinical trials for genetic based therapies

4. “Current therapy is not sufficient for recovery”

5. ALS • Paralysis and death within • 2-5 years • There is no cure and no • effective treatments • SLOW the disease • Stop, reverse, prevent/cure

6. Patient/family perspective • Too little focus on rare diseases • Too little funding • Research moves too slowly • Breakthroughs come too late for many

7. Not enough focus or funding • Rare diseases • Limited research funding (governmental and non-governmental)

8. Challenges to therapy development • Rare diseases • Limited research funding (governmental and non-governmental) • Bottlenecks in moving from the lab into humans • Limited interest from pharmaceutical companies • Designer drugs • Finding potential study subjects • Exclusion of potential study subjects • “disenfranchised” groups

9. $19.4 MDA’s Research Portfolio - Bottlenecks Translational Research “Preclinical Drug Development” Drug Screening Target Identification Basic Research “Proof-of-Principle” Testing in Animals Clinical Research Including Trials $54.4 $16.9 $5.0 $7.6 MDA Funding in Millions

10. Challenges to therapy development • Rare diseases • Limited research funding (governmental and non-governmental) • Bottlenecks in moving from the lab into humans • Limited interest from pharmaceutical companies • Designer drugs • Finding potential study subjects • Exclusion of potential study subjects • “disenfranchised” groups

11. Challenges to Therapy Development: Required Resources • Burden of disease studies • Patient registries • Natural history studies • Genotyping • Biomarkers • Clinically meaningful outcome measures

12. Challenges to developing outcome measures: - define “clinically meaningful” - age of individuals - stage of disease - physical abilities - cognitive abilities

13. Challenges to therapy development: “legal” issues • Funding agency perspective • Scientific due diligence • Financial due diligence • Tech transfer/IP issues • Delays in initiation of clinical trials due to the time it takes for IRB approvals

14. Challenges to therapy development: “technology” issues • Electronic communication is impacting the conduct of clinical trials (i.e., traditional research moves too slowly) • Social networking and on-line forums such as “Patients Like Me” --- sharing of information • Off-label use of approved drugs

15. What’s needed • More focus on and funding for rare diseases • Conduct needed studies – burden of disease, natural history studies, registry development, biomarker development, etc • Speed up the process • Reduce bottlenecks • Expand studies to include as many patients as possible