Transcript Pharmacogenomics: Implications for CNS drug

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
Rare diseases
Advances in Duchenne
muscular dystrophy
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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
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Not enough focus or funding
NIH 2008 Spending for Various Diseases
Anthrax
Smallpox
Infertility
Cystic Fibrosis
Cervical Cancer
Multiple Sclerosis
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Rare diseases
Spinal Muscular Atrophy
Myasthenia Gravis
Charcot-Marie-Tooth Disease
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Limited research
funding
(governmental
and nongovernmental)
Myotonic Dystrophy
Facioscapulohumeral Muscular Dystrophy
Duchenne/Becker Muscular Dystrophy
Muscular Dystrophy
Amyotrophic Lateral Sclerosis
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20
40
60
80
100
120
140
160
180
Millions of Dollars
NIH 2008 Spending on Various Diseases
Diabetes
Heart Disease
Cancer
Spinal Muscular Atrophy
Muscular Dystrophy
Amyotrophic Lateral Sclerosis
0
1000
2000
3000
Millions of Dollars
4000
5000
6000
Challenges to therapy
development
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Rare diseases
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Limited research funding
(governmental and nongovernmental)
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
MDA’s Research Portfolio - Bottlenecks
Basic Research
Drug Screening
Target Identification
“Proof-of-Principle”
Testing in Animals
Translational Research
“Preclinical Drug
Development”
Clinical Research
Including Trials
$54.4
$19.4
$16.9
MDA Funding in Millions
$5.0
$7.6
Challenges to therapy
development
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Rare diseases
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Limited research funding
(governmental and nongovernmental)
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
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Challenges to developing
outcome measures:
- define “clinically
meaningful”
- age of individuals
- stage of disease
- physical abilities
- cognitive abilities
Challenges to therapy
development: “legal” issues
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Funding agency perspective
Scientific due diligence
 Financial due diligence
 Tech transfer/IP issues
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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
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Off-label use of approved drugs
What’s needed
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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
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Reduce bottlenecks
Expand studies to include as many
patients as possible