1. Rare Diseases and FDASIA
Gayatri R. Rao MD, JD
Director
Office of Orphan Products Development (OOPD), FDA
Rare Disease Congressional Caucus Briefing
November 14, 2012

2. Office of the Commissioner
Where in the FDA?
Office of the Commissioner
(OC)
Office of Medical Products and Tobacco
OMPT OF
Office of Foods OO
Office of Operations
OGROP
Office of Global Regulatory Operations & Policy
CDER
CBER
CDRH
Center for Devices and Radiological Health
CTP
Center for Tobacco Products
OSMP
Office of Special Medical Programs
OOPD
Office of Orphan Products Development
Center for Drug Evaluation and Research
Center for Biologics Evaluation and Research
RDP Rare Diseases Program
For Complete FDA Organizational Chart see:

3. Orphan Drug Designation
Office of the Commissioner
(OC)
Office of Medical Products and Tobacco
OMPT
Step 1:
Orphan Drug Designation
Humanitarian Use Device (HUD) Designation
OOPD
Office of Orphan Products Development
OSMP
Office of Special Medical Programs
CDER
Center for Drug Evaluation and Research
CBER
Step 2:
Marketing Application -
NDA / BLA / HDE
Center for Biologics Evaluation and Research
For Complete FDA Organizational Chart see:
CDRH
Center for Devices and Radiological Health

4. What is the Advantage to Designation?
When a drug or biological product is designated an orphan, certain financial incentives can flow:
Tax Credits – 50% of clinical trials costs
Waiver of User Fees - $1.9 M
7-year Marketing Exclusivity
When a device is designated as a HUD, device is eligible for an alternate pathway to market – Humanitarian Device Exemption (HDE)
Exempt from an effectiveness showing; in lieu need only show probable benefit

5. Orphan Drug Highlights
Designations
~ 3700 Designation requests received
~ 2550 Products granted designation (~70%)
Approvals
>400 Drugs brought to market
FY 2011 – 26; FY 2012 (to date) – 17
Designations
Approvals
Year
Number of Orphan Designations and Approvals

6. Size of Populations (1983-2011)
Designations
Approvals
Number of Designations and Approvals
0-9
10-19
20-29
30-39
40-49
50-59
60-69
70-79
80-89
90-99
200 & up
US prevalence (in thousands) of diseases for which products received an orphan designation

7. HUD Designation Program
Devices labeled for peds
Berlin Heart EXCOR® Pediatric Ventricular Assist Device (VAD)
NeuRx DPS™, Diaphragm Pacing System
Elana Surgical Kit
Total
2011
# of HUDs Received
283 21
# of HUDs Designated
183
(65%) 17
(majority rec’d in 2011)
# of HDEs Approved 56 6
3 labeled for peds
1 funded by OPG pgm
Source: OOPD Database
Berlin Heart EXCOR® Pediatric VAD received 3-year funding for ~$1.19M which funded a pivotal study in support of HDE approval
2012 – To date
20 HUDs received
12 HUDs designated

8. FDASIA and PDUFA Performance Goals: Provisions Related to Rare Diseases
Expedited Approval for Serious or Life-Threatening Diseases/ Conditions
Accelerated Approval
Breakthrough Therapies
External Experts
Patient-Focused Drug Development
Rare Pediatric Disease Voucher Program
Meetings and Guidance Development
Humanitarian Device Exemptions
Reauthorization of Grants:
Orphan Products Grant Program - $30M/year
Pediatric Devices Consortia Grant Program - $5.25M/year

9. Expedited Approval for Serious or Life-Threatening Diseases/ Conditions: Accelerated Approval
Based on a determination that the product has an effect on a:
Surrogate endpoint that is reasonably likely to predict clinical benefit OR
Clinical endpoint that can be measured earlier than irreversible morbidity or mortality, that is reasonably likely to predict effect on irreversible morbidity or mortality or other clinical benefit
Takes into account severity, rarity, or prevalence, as well as lack of alternative treatments

10. Expedited Approval for Serious or Life-Threatening Diseases/ Conditions: Breakthrough Therapy
Designate drug as a breakthrough therapy if:
Intended to treat a serious or life-threatening disease/condition AND
Preliminary clinical evidence indicates that drug may demonstrate substantial improvement over existing therapies on 1 or more clinically significant endpoints
Submit request for designation with original IND or later
If designated:
Eligible for everything Fast Track receives
Also get more interactive involvement with review division to help guide efficient yet scientifically appropriate trial design 10

11. External Experts
Ensure that opportunities exist for consultations with stakeholders for topics, including for example:
Severity of rare diseases
Unmet medical need associated with rare diseases
Willingness and ability of individuals with a rare disease to participate in clinical trials
Assessment of benefits and risks of therapies to treat rare diseases
Develop and maintain a list of external experts for consultation 11

12. Patient-Focused Drug Development
FDA to conduct 20 meetings on different disease areas to obtain patient perspective on disease severity or unmet medical need
Sept. 24, 2012 – Published a preliminary list of nominated disease areas and the criteria used for nomination
Included rare diseases (e.g., sickle cell disease, amyloidosis, hereditary angioedema)
Oct. 10, Kicked off bi-monthly process consultation meetings
Oct. 25, 2012 – Open public meeting to discuss the proposed set of disease areas

13. Rare Pediatric Disease Priority Review Vouchers
Similar to the Tropical Disease Priority Review Voucher Program
Uses priority review vouchers as an incentive to develop drugs and biologics for “rare pediatric diseases”
Authorized until “the last day of the 1-year period that begins on the date that FDA awards the third rare pediatric disease priority voucher” 13

14. Meetings and Guidance Public Meetings Guidance Development
Issues in clinical trials for drugs for rare diseases (e.g., endpoint selection, use of surrogate endpoints, patient reported outcomes)
Ways to encourage/accelerate development of new therapies for pediatric rare diseases
Guidance Development
PDUFA Performance Goal (IX.E.): FDA, on an ongoing basis, will develop guidance to address issues to facilitate development of drugs for rare diseases (e.g., study design, endpoints, statistical analysis, etc.)
FDASIA provisions related to accelerated approval, breakthrough therapies, etc. likewise call for guidance development

15. Humanitarian Device Exemption
Expands profit-making to HDE devices that
Don’t occur in pediatrics OR
Occurs in pediatrics in such number that development of device is “impossible, highly impracticable, or unsafe“
Changes the definition of annual distribution number (ADN)
Equals the # of devices needed to treat/diagnose/cure 4,000 individuals 15

16. Questions? For more information on OOPD’s programs, check out