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 DirectorMDA
Rare diseases
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
“Current therapy is not sufficient for recovery”
ALS •Paralysis and death within 2-5 years•There is no cure and no effective treatments•SLOW the disease•Stop, reverse, prevent/cure
Patient/family perspective
Too little focus on rare diseases
Too little funding Research moves too slowly Breakthroughs come too late
for many
Not enough focus or funding
Rare diseases Limited research
funding (governmental and non-governmental)
0 20 40 60 80 100 120 140 160 180
Millions of Dollars
Amyotrophic Lateral Sclerosis
Muscular Dystrophy
Duchenne/Becker Muscular Dystrophy
Facioscapulohumeral Muscular Dystrophy
Myotonic Dystrophy
Charcot-Marie-Tooth Disease
Myasthenia Gravis
Spinal Muscular Atrophy
Multiple Sclerosis
Cervical Cancer
Cystic Fibrosis
Infertility
Smallpox
Anthrax
NIH 2008 Spending for Various Diseases
0 1000 2000 3000 4000 5000 6000
Millions of Dollars
Amyotrophic Lateral Sclerosis
Muscular Dystrophy
Spinal Muscular Atrophy
Cancer
Heart Disease
Diabetes
NIH 2008 Spending on Various Diseases
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
Basic Research Drug ScreeningTarget Identification
“Proof-of-Principle”Testing in Animals
Translational Research“Preclinical Drug
Development”Clinical ResearchIncluding Trials
MDA Funding in Millions
$54.4
$16.9
$7.6
$19.4
$5.0
MDA’s Research Portfolio - Bottlenecks
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
Challenges to Therapy Development: Required Resources
Burden of disease studies Patient registries Natural history studies Genotyping Biomarkers Clinically meaningful
outcome measures
Challenges to developing outcome measures:
- define “clinically meaningful”- age of individuals- stage of disease- physical abilities- cognitive abilities
Challenges to therapy development: “legal” issues
Funding agency perspectiveScientific due diligenceFinancial due diligenceTech transfer/IP issues
Delays in initiation of clinical trials due to the time it takes for IRB approvals
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
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