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The Orphan Drug Act and the Development of Products for Rare Diseases
Mathew T. Thomas, MDOffice of Orphan Products Development
Food and Drug AdministrationTelephone: 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
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.
The U.S. Orphan Drug Act (ODA) The U.S. Orphan Drug Act (ODA) Signed in 1983Signed in 1983
• 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 Drug?What is an Orphan Drug?
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
0
20
40
60
80
100
120
140
160
180
1983 1985 1987 1989 1991 1993 1995 1997 1999 2001 2003 2005 2007
Year
Num
ber o
f Orp
han
Des
igna
tions
or A
ppro
vals
• As of 2009, 3030 designation applications• 2122 orphan product (drugs and biologics) designations
Approvals
Designations
• 2009: 353 Approved Orphan Products!• About 1/3rd of all FDA Approvals
Comparison of orphan and non orphan approvals over 1984 - 2008
0
50
100
150
200
250
1984 - 1988 1989 - 1993 1994 - 1998 1999 - 2003 2004 - 2008
Num
ber o
f app
rova
ls
0
5
10
15
20
25
30
35
Percentage
orphan original BLAs Orphan NMEsNon orphan original BLAs Non Orphan NMEsProportion of orphans to non orphans
Impact of the ODA on orphan approvals
Diseases/Conditions Targeted by Designated Orphan Drugs*
36%
11%7%7%
6%
5%
4%
4%
4%
2%1%2%2%
2%
3%2%
2%
OncologicMetabolicHematologic-immunologicNeurologicInfectious/parasiticCardiovascularTransplantationGastrointestinalRespiratoryEndocrinologicDermatologicOphthalmicMusculoskeletalInjury/poisoningPerinatalCongenital abnormalitiesOthers
• 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
What are the Incentives for Orphan-Drug Designation?
• 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
Orphan Products Grants ProgramOrphan Products Grants Program
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
57
90 9296
105
87
4844
64
78
101
54
69
55 5865
15
28 2617 19 21 20
12 15 15 18 20 21
5 7 103
11 8 6 3 3 3 2 1 2 1 1 312
2016
0
20
40
60
80
100
120
'93 '94 '95 '96 '97 '98 '99 '00 '01 '02 '03 '04 '05 '06 '07 '08Number of grant applications receivedNumber of new grants awardedNumber 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 Drug
(Possible Blockbuster)
Other Drug NDA/BLA
Priority Review Voucher
Marketing Approval for
Tropical Disease Drug
Successful NDA/BLA
Big PhRMA Company
Voucher generation
Voucher Transfer $$$
Voucher Redemption FASTER?
What about Medical Devices?What about Medical Devices?
Humanitarian Use Device (HUD)Humanitarian Use Device (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