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: mathew.thomas@fda.hhs.gov

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