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