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Orphan Drugs – 2011
What’s Happening?
Women in BIO
Marlene E. Haffner, MD, MPH
[email protected]
301 984 5729 - Office
301 641 4268 – cell
November 1, 2011
Haffner Associates, LLC
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LOTS!
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INCENTIVES
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7 Years Exclusive Marketing
Waiver of PDUFA Filing Fee
Assistance of OOPD
Tax Credits – 50 % of clinical development
costs
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– one year fall back; 20 year carry forward
Grant Support
Recommendations from Brownback Brown
Report
Associate Director for Orphan Drugs - CDER
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Accomplishments
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~ 390 products approved
> 2000 designations
> 15,000,000 patients potentially
treated
> 45 products approved through the
grants program
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2009 Emergence of Big PhRMA
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GSK
Novartis
Pfizer
Genentech/Roche
Sanofi
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Biotech and Orphan
Products
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Began with Genentech – hGH - and
has progressed
Now the emergence of “molecular
medicine”
Personalized medicine – genetic
knowledge fits well with orphan drug
development
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1992 Regulations
2011 NPRM
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2011 NPRM released week of October
21st
Codifies practices already in place
Medically plausible subsets vs the
disease process
Better defines the designation process
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Review and Approval of
Orphan Products
Orphan Products must be Safe and Effective for their
intended use
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Is that possible?
FDA has demonstrated flexibility
90 of 135 non-oncology approvals approved with non
standard approaches – NORD study
 Smaller clinical trials
 Historical controls
 Single arm/non-randomized
 Case-by-case
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Current Issues and Activities
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Safety concerns
REMS
Cost
Reimbursement
Large # of orphan programs and
activities globally
Increasing coordination with the EU
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Safety
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Orphan Products approved based on small clinical trials
Infrequent adverse events will not be seen
Until the last 3 – 4 years “there had been no safety
concerns with orphan products”
 That has changed – e.g. EPO – 25 years following
initial approval; Botulinum toxin - black box warning
 Virtually all new orphan approvals carry a REMS
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REMS – Risk Evaluation
and Mitigation Strategy
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Orphan Products with REMS –
Nplate – no safety signals in clinical
trials
 Botulinum toxin – new findings
 FDA (and Congress) erring on the side
of safety
 Allows FDA to approve some products
which would not previously have been
approved
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Cost of Orphan Drugs
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US expenditure for drugs - 2.2% of GDP in 2000; will
be 5.6% in 2030
Newest products in the health care arena are Biotech
Biotech products are expensive – whether they are
orphan products or not
Because of some high profile examples, orphan
products are often sighted as expensive
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Some orphan products are expensive; most
are not
Economies of scale for a small population is
not present – need to explain better to the
public
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Reimbursement
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Must figure reimbursement strategies as drug
development proceeds. This involves
working with CMS and individual insurance
companies
Must explain to patient groups the rationale
for cost of the product if high. Cost may by
necessity be high
Some EU member states very conservative in
reimbursement
Recent unfortunate examples
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Personalized Medicine
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Human genome allows more targeted
therapies
Many of these will subdivide larger
diseases into smaller ones which may
be orphan diseases – gene mutations
NIH TRND program
Repurposing of old drugs
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What does this mean for
my company?
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What is your strategy?
Orphan Products generally treat life
threatening diseases – may mean faster
approval
Common application format in EU and US –
saves money
Tax incentives
Exclusivity
Waiver of PDUFA Filing Fee – $1.8 mil in
2011
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Examples of Office of
Orphan Products
Assistance
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Envenomation
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Envenomation – OOPD convinced
review division to broaden thinking re
indication – approved product in 2011
Other envenomation products being
developed
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Narcolepsy
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How should the product be DEA
scheduled?
Without the intervention of OOPD the
product may not have been developed
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Prevalence and # of
clinical trials
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A disease with < 100 patients in the US
Hard, if not impossible, to do TWO
placebo controlled trials
When to use historical controls
How to develop phase 1,2,3 trials
Inviting the OOPD to meetings with
the division
Need for Natural History studies
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Toxicity testing
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The disease is lethal at a very young age
What are the considerations
Can toxicity testing be done following
clinical trials in humans
Need new methodologies for
preclinical drug development
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Roll of the Associate Director
for Orphan Products in CDER
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Primarily policy/consistency
Evaluating new science with regards to
Orphan Product development
Biomarkers
Close collaboration with the OOPD
Hopefully will grow in size
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A New Day in OOPD
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Appointment of new Acting OOPD
Director – Gayatri Rao, MD, JD
NPRM issues 19 years following initial
regulations
Increasing # of companies join the
drive toward rare disease therapies
NIH efforts
Commitment of FDA with Associate
Director for Orphan Products
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?
Marlene E. Haffner, MD, MPH
Haffner Associates, LLC
[email protected]
www.mhaffner.com
301-984-5729
301-641 4268
Haffner Associates, LLC
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