FDAs Recent Developments for Orphan Drugs

1
FDAs Recent Developments for Orphan Drugs
Humanitarian Devices

• Marlene E. Haffner, M.D., M.P.H.
• Director, FDA Office of Orphan Products
  Development
• 2006 NORD Annual Conference
• September 28th-October 1st
• Hyatt-Regency
• Bethesda, Maryland

2
The U.S. Orphan Drug Act Signed in 1983

• Established the public policy that the Federal
  Government could/would assist in the development
  of treatment for rare diseases

3
Worldwide Orphan Drug Development Opportunities

• Orphan drug development programs being carried
  out in locations throughout the world.
• Provide opportunities to work together toward
  common goals.
• Despite many difficulties, smaller populations
  may be easier to work with.
• Cutting edge technologies are often used first in
  the development of orphan drugs.

4
Defining an Orphan Disease

• U.S.
• E.U.
• Japan
• Australia
• Norway
• Sweden
• S. Korea

• 11 300
• 12 000
• 12 500
• 115 000
• 110 000
• 110 000
• 123 000

5
Unique/Cutting Edge Orphan Products

• PEG-ADA First use of pegylation was in this
  orphan product used in enzyme replacement therapy
  for ADA deficiency in patients with severe
  combined immunodeficiency (SCID).
• Liposomal amphotericin B Early use of liposomal
  process in drug development.
• Fabrazyme Enzyme replacement therapy to treat
  Fabry disease. Orphan grant funding.
• Human Growth hormone Blood Coagulation
  Products Recombinant DNATechnology.

6
Since 1983

• 1390 active designated orphan products
• 295 approved orphan products
• 231 drugs
• 64 biologics
• Available to 15 million rare disease patients in
  the United States.

7
Time From Designation to Marketing Approval
(1983-2005)
Top 7 categories of drugs by number of
marketing approvals
8
Number of Orphan Drugs Approved by FDA per Year
(1983-2005)
As of 10 May 2006
9
Number of Marketing Approvals by Year of
Designation (1983-2005)
As of 10 May 2006
10
Number of Orphan Drugs Approved vs. all FDA
Approvals (2000-2005)
As of 10 May 2006
11
41 Products Approved Through Research Funded By
Orphan Grants Program

• Examples
• Human Botulism Immune Globulin (BIG) injection
  to treat infant botulism.
• Alpha-Galactosidase-A Therapy for Fabry Disease
• Deep Brain Stimulation to assist patients with
  Dystonia.

12
Recent Orphan Grant Studies

• 18 new grant studies funded. FY06 14 million
  grant budget.
• 2 Grant studies funded in cooperation w/
  Pediatric Heart Network.
• Elaprase approved 2006. Enzyme replacement
  therapy for patients with MPS II (Hunter
  Syndrome). Orphan designation Nov 2001 2005
  orphan grant study by Shire Human Genetic
  Therapies, Inc.

13
Recent Orphan Grant Studies

• Investigating Cystic Fibrosis Mechanism
  successful in removing Premature stop signals
  responsible for these genetic errors.
• Study of Muscular Dystrophy Therapy Mechanism
  successful in removing Premature stop signals
  responsible for these genetic errors.

14
Responsibilities of the Office of Orphan Products
Development in Evaluating Humanitarian Use
Devices (HUD)
15
What is a HUD?

• A Humanitarian Use Device (HUD) is a medical
  device intended to benefit patients in the
  diagnosis and/or treatment of a disease or
  condition that affects or is manifested in fewer
  than 4,000 patients per year in the United
  States.
• HUD designation by OOPD.

16
What is an HDE?

• A Humanitarian Device Exemption (HDE) is a
  provision that exempts sponsors of devices for
  orphan diseases from the more rigorous
  effectiveness requirements of the medical device
  law, provided the device meets safety conditions
  and will not expose patients to significant or
  unreasonable risk.
• Responsibility of FDA Center for Devices and
  Radiological Health (CDRH).

17
How is an HDE Granted?

• Two-step process
• HUD designation request submitted to OOPD.
• After HUD designation, an HDE application is
  submitted to the Office of Device Evaluation, in
  the FDA Center for Devices Radiological Health
  (CDRH).

18
Statistics

• Since October 1996
• 172 Requests received.
• 126 Devices designated as HUDs by OOPD.
• 39 HUDs approved as HDEs by CDRH

19
First Artificial Heart Receives FDA Humanitarian
Device Exemption (HDE)

• OOPD designated AbioCor implantable artificial
  heart as a Humanitarian Use Device in 2003.
• HDE approved September 6, 2006.

20
HUD to HDE to PMA

• PreMarket Approval (PMA) has been granted to
  several Humanitarian Device Exemptions designated
  by OOPD and approved in CDRH
• CardioSEAL Septal Occlusion System for patients
  with complex ventricle physiology.
• CardioSEAL Septal Occlusion System for infants
  children with complex ventricular septal defects
  (VSD) that cannot be closed w/ standard surgical
  approaches.
• BioGlue Surgical Adhesive For use as an
  adjunctive device in the surgical repair of
  acute, aortic dissections.

21
New Initiative

• Parallel DevelopmentEU/US

22
Compatibility

• Commonality in 90 of decisions to grant orphan
  drug status thus far
• With few exceptions, very similar regulatory
  frameworks on the designation review process
• Potentially lessening regulatory review burden
  and shortening review time
• EC/EMEA-FDA Confidentiality Arrangement to
  exchange regulatory information in effect till
  2010

23
Comparing US/EU Criteria for Orphan Drug
Designation

• In Common
• Epidemiological (prevalence) 7/10,000 US
  5/10,000 EU
• Economic unlikely to generate sufficient return
  on investment
• Medical plausibility of the condition
• Biological/pharmacological rationale
• EU Only
• Restricted to Serious life threatening
  diseases.
• Assumption of significant benefit
• Existing methods of treatment are not satisfactory

24
Foreseeable for Tomorrow

• Conceivably, in many cases
• Same (or very similar) designation request
  package may be submitted to both EMEA and FDA.
• COMP-OOPD joint designation review or mutual
  adoption of review opinion may be feasible.
• Joint issuance or adoption of common guidance
  documents on orphan-drug designation

25
Beyond Tomorrow

• Regulatory EMEA-FDA partnership to provide joint
  protocol assistance for orphan drugs
• Desirable to expand pilot EMEA-FDA Parallel
  Scientific Advice Program to offer guidance on
• Adequacy of preclinical development program
• All phases of clinical development

26
OOPD Web Site
http//www.fda.gov/orphan

• Overview of the FDA Office of Orphan Products
  Development
• Guidelines for designation application
• List of designated and approved orphan products
• Grant application information
• List of ongoing orphan grant studies
• Phone Contact 301-827-3666 or 1-800-300-7469

27
Meet the OOPD Staff