pharmacogenomics: implications for cns drug development in the 21st century challenges for...
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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
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Rare diseases
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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
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“Current therapy is not sufficient for recovery”
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ALS •Paralysis and death within 2-5 years•There is no cure and no effective treatments•SLOW the disease•Stop, reverse, prevent/cure
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Patient/family perspective
Too little focus on rare diseases
Too little funding Research moves too slowly Breakthroughs come too late
for many
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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
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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
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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
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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
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Challenges to Therapy Development: Required Resources
Burden of disease studies Patient registries Natural history studies Genotyping Biomarkers Clinically meaningful
outcome measures
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Challenges to developing outcome measures:
- define “clinically meaningful”- age of individuals- stage of disease- physical abilities- cognitive abilities
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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
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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
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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