The Orphan Drug Act and the Development of Products for Rare Diseases
Mathew T. Thomas, MD Office of Orphan Products Development Food and Drug Administration Telephone: 301-827-3666 Email: [email protected]
The Office of Orphan Drug Development at the FDA works closely and in collaboration with the Office of Rare Disease Research Presentation Outline
• Orphan Drug Act (1983) • “Orphan” drugs and diseases • Functions of the Office of Orphan Product Development (OOPD) • Financial incentives of orphan drug status • OOPD grant program • Incentive for tropical disease products • OOPD device regulation TheThe U.S.U.S. OrphanOrphan DrugDrug ActAct (ODA)(ODA) SignedSigned inin 19831983
US Congress established the public policy that the Federal Government could/would assist in the development of products for the diagnosis, prevention or treatment of rare diseases or conditions. WhatWhat isis anan OrphanOrphan Drug?Drug?
• A drug (or biologic) intended to treat a rare disease or condition affecting fewer than 200,000 persons in the United States
or
• A drug (or biologic) which will not be profitable within 7 years following approval by the U.S. Food & Drug Administration What is an Orphan Disease? • Affects <200,000 persons in the US
• Affects >200,000 in US, no expectation that therapeutic development costs will be recovered from sales in the US
• 6,000 rare diseases
• Affects 25 million Americans Principle functions of the FDA Office of Orphan Product Development.
1. Designate drugs as having “orphan status”
2. Award grants for clinical development
3. Regulate orphan devices through the Humanitarian Use Device (HUD) program
4. Serve as FDA’s rare disease focal point with outreach to patient groups and industry What OOPD Does NOT do…
• Pricing
• Access/Insurance
• Conduct of intramural research (preclinical or clinical) Impact of the ODA on number of orphan designations • As of 2009, 3030 designation applications • 2122 orphan product (drugs and biologics) designations 180
160
140 Approvals
120 Designations 100 80
60
40 1983 1985 1987 1989 1991 1993 1995 1997 1999 2001 2003 2005 2007 20
Number ofNumber Orphan Designations or Approvals 0
Year Impact of the ODA on orphan approvals
• 2009: 353 Approved Orphan Products! • About 1/3rd of all FDA Approvals
Comparison of orphan and non orphan approvals over 1984 - 2008
250 35
30 200
25 Percentage
150 20
100 15 10 50 Number of of approvals Number 5
0 0 1984 - 1988 1989 - 1993 1994 - 1998 1999 - 2003 2004 - 2008
orphan original BLAs Orphan NMEs Non orphan original BLAs Non Orphan NMEs Proportion of orphans to non orphans Diseases/Conditions Targeted by Designated Orphan Drugs*
Oncologic 2% 2% 1% 2% Metabolic 2% 2% Hematologic-immunologic 2% Neurologic 3% Infectious/parasitic Cardiovascular 4% 36% Transplantation 4% Gastrointestinal Respiratory 4% Endocrinologic Dermatologic 5% Ophthalmic 6% Musculoskeletal 7% 11% Injury/poisoning 7% Perinatal Congenital abnormalities Others What are the Incentives for Orphan-Drug Designation?
• 7-year marketing exclusivity • Tax credits (up to 50% of clinical development costs) • Exemption/Waiver of application (filing) fees • OOPD assistance during the development process OrphanOrphan ProductsProducts GrantsGrants ProgramProgram
• 90-100 applications per year from domestic or foreign, public or private, for-profit or nonprofit entities • Fund about 10-20 new grants per year • Supports academic and industry sponsored research
• Orphan designation is not a grant requirement Composition of Orphan Grants
• 25% have a Phase 1 component • 55% have a Phase 2 component • 20% have a Phase 3 component • About 25% of funding goes to companies • About 50% are company/academic institution collaboration Grants Statistics
• 1983: $500,000
• To date: $261 million for 508 grants
• Current annual budget ≈ $14 million
Is the OPD Grant Program Successful?
• YES!
• 44 FDA approved products funded through the OOPD Grants Program
• Generation primary research articles Annual Number of OPD Grant Applications
120 105 101 96 100 90 92 87 78 80 69 64 65 57 58 54 55 60 48 44 40 28 26 21 21 20 19 20 18 20 15 17 16 15 15 20 11 12 12 10 8 5 7 6 3 3332 1 2 113 0 '93 '94 '95 '96 '97 '98 '99 '00 '01 '02 '03 '04 '05 '06 '07 '08 Number of grant applications received Number of new grants awarded Number of competitive continuation grants awarded FDAAA 2007 incentive for tropical disease drugs • Drugs for diseases that are common elsewhere but rare here qualify for orphan status
• Little to no development for past 50+ years
• Priority Review Vouchers (PRVs) Priority Review Voucher Mechanics
Tropical Disease Marketing Drug Approval for Successful NDA/BLA Tropical Disease Drug
Voucher generation Priority Review Voucher
Voucher Transfer $$$ (Possible Big PhRMA Blockbuster) Company Other Drug ? FASTER Voucher Redemption NDA/BLA WhatWhat aboutabout MedicalMedical Devices?Devices? HumanitarianHumanitarian UseUse DeviceDevice (HUD)(HUD)
• HUD = Device treating a disease affecting <4,000 in the US per year (incidence)
• A HUD then undergoes further FDA/CDRH review to determine if it qualifies for a Humanitarian Device Exemption (HDE) Humanitarian Device Exemptions (HDE)
• HDE similar to a pre-market approval (PMA) but is exempt from the effectiveness requirement – Not for profit (unless pediatric device) – Device has to be used with IRB approval – No comparable device marketed
• FDA/CDRH approval of a HDE authorizes marketing of the HUD Accomplishments: Is the Orphan Drug Act a Success?
• 2100+ designations • 353 drug and biologic approvals • 44 product approvals from grants • ~ 132 HUD requests granted • 44 HDE approved via CDRH Questions