Orphan Products Grants Program OverviewOrphan Products Grants Program Overview

Orphan Clinical Grant Orphan Clinical Grant ProgramProgram

FDA/EMA Orphan Designation & Grant FDA/EMA Orphan Designation & Grant WorkshopWorkshopOctober 12, 2012October 12, 2012

Linda C. Ulrich, M.D.Linda C. Ulrich, M.D.Director, Pediatric Device Consortia Grant ProgramDirector, Pediatric Device Consortia Grant ProgramFDA/OOPDFDA/OOPD

OOPD Grants ProgramsOOPD Grants Programs PDCPDC Orphan Clinical Grants ProgramOrphan Clinical Grants Program

Other Sources of FundingOther Sources of Funding

Outline

2

Challenges to Overcome in Developing Rare Disease Treatments

Patient AccrualPatient Accrual Geographic Dispersion of PatientsGeographic Dispersion of Patients

Return on Investment Return on Investment Cost of DevelopmentCost of Development

Statistical SignificanceStatistical Significance

Grants Programs in OOPDGrants Programs in OOPD

1.1. Pediatric Device Consortia Grant Program Pediatric Device Consortia Grant Program (New as of FY 2009)(New as of FY 2009)

2.2. OPD Clinical Research Grants (R01) for OPD Clinical Research Grants (R01) for Orphan DiseasesOrphan Diseases

Pediatric Device Consortia Pediatric Device Consortia Grant ProgramGrant Program

PDC Grant Program

Established from FDAAA 2007Established from FDAAA 2007

Does not have to be Orphan – Administered by Does not have to be Orphan – Administered by OOPD, but encompasses devices used in all OOPD, but encompasses devices used in all pediatric diseases, not just rare diseases. pediatric diseases, not just rare diseases.

Receipt date was May 2, 2011 – Paper Receipt date was May 2, 2011 – Paper submissionsubmission

See RFA at See RFA at http://grants.nih.gov/grants/guide/rfa-files/RFA-FD-11-002.html http://grants.nih.gov/grants/guide/rfa-files/RFA-FD-11-002.html

PDC Grant ProgramPDC Grant Program

Establish nonprofit consortia to stimulate pediatric Establish nonprofit consortia to stimulate pediatric device developmentdevice development

Not a direct research grantNot a direct research grant fund nonprofit consortia that fund nonprofit consortia that supportsupport pediatric pediatric

device developersdevice developers

Results-drivenResults-driven aimed at moving products forward along the aimed at moving products forward along the

development continuum.development continuum.

Progress So Far…..Progress So Far…..

Over Over 175 175 pediatric device projects have been assisted pediatric device projects have been assisted by the pediatric device consortia since October of by the pediatric device consortia since October of 2009.2009.

OOPD supported 5 consortia in FY 2012OOPD supported 5 consortia in FY 2012 judged on the organizational capacity of their proposed judged on the organizational capacity of their proposed

consortiums to exert a sustained, powerful influence on the consortiums to exert a sustained, powerful influence on the field of pediatric device development, as well as an field of pediatric device development, as well as an assessment of potential device projectsassessment of potential device projects

Linda Ulrich Linda Ulrich ((Linda.Ulrich@fda.hhs.gov)Linda.Ulrich@fda.hhs.gov)

Debra Lewis (Debra Lewis (Debra.Lewis@fda.hhs.govDebra.Lewis@fda.hhs.gov) )

*For more device information, go to*For more device information, go tohttp://www.fda.gov/ForIndustry/http://www.fda.gov/ForIndustry/DevelopingProductsforRareDiseasesConditions/DevelopingProductsforRareDiseasesConditions/PediatricDeviceConsortiaGrantsProgram/default.htm PediatricDeviceConsortiaGrantsProgram/default.htm

PDC Contacts

Orphan Products Grants Orphan Products Grants ProgramProgram

Goal:Goal: To encourage To encourage clinicalclinical development of products, development of products, including drugs, biologics, medical devices, or medical including drugs, biologics, medical devices, or medical foods, for use in rare diseases.foods, for use in rare diseases.

The disease must be rare as defined in the Act (For diseases The disease must be rare as defined in the Act (For diseases affecting <200,000 persons in the U.S.)affecting <200,000 persons in the U.S.)

Orphan Products Grants Program

Unique Program

Close to the Regulatory aspect Close to the Regulatory aspect Have individuals in our office that have come Have individuals in our office that have come

from many backgrounds including the review from many backgrounds including the review divisionsdivisions

Review Divisions’ inputReview Divisions’ input IOM (Institute of Medicine) identified this as a IOM (Institute of Medicine) identified this as a

successful attribute of the program (not as easily successful attribute of the program (not as easily implemented across other agencies)implemented across other agencies)

Orphan Products Grants Program A practical program: A practical program:

Goals are advancing marketing approvals and relevant publications that Goals are advancing marketing approvals and relevant publications that impact care for rare diseasesimpact care for rare diseases

Approximately 100 applications per yearApproximately 100 applications per year

Competitive grant program – ~15% success Competitive grant program – ~15% success Fund about 10-15 new grants per yearFund about 10-15 new grants per year

Request for Application (RFA) available at www.fda.gov/orphan Request for Application (RFA) available at www.fda.gov/orphan

Application, review, and scoring much like NIH grant applicationApplication, review, and scoring much like NIH grant application

Electronic submissions: Grants.govElectronic submissions: Grants.gov

Requirements Eligibility:Eligibility:

AcademicAcademic and and industryindustry sponsored research sponsored research Domestic or foreign, public or private, for-profit or nonprofit entities Domestic or foreign, public or private, for-profit or nonprofit entities Any entity except DHHS Federal agencies Any entity except DHHS Federal agencies

Requirements:Requirements:

Clinical studyClinical study of an orphan disease or condition of an orphan disease or condition A study must advance info towards a market approvalA study must advance info towards a market approval Must have active IDE (not on clinical hold)Must have active IDE (not on clinical hold) Good Clinical Practices (GCP)Good Clinical Practices (GCP) Human Subjects Assurance from OHRP (Office of Human Research Protections) “Federal-Human Subjects Assurance from OHRP (Office of Human Research Protections) “Federal-

Wide Assurance or FWA” (www.hhs.gov/ohrp)Wide Assurance or FWA” (www.hhs.gov/ohrp) IRB approvalIRB approval Evidence that drug product is sufficiently available Evidence that drug product is sufficiently available

Funding dependent on Funding dependent on quality of applicationquality of application and availability of Federal funds and availability of Federal funds

For more information visit the OPD Grant Program website: For more information visit the OPD Grant Program website: http://www.fda.gov/ForIndustry/DevelopingProductsforRareDiseasesConditions/http://www.fda.gov/ForIndustry/DevelopingProductsforRareDiseasesConditions/WhomtoContactaboutOrphanProductDevelopment/ucm134580.htmWhomtoContactaboutOrphanProductDevelopment/ucm134580.htm

The current annual budget for grant funding is The current annual budget for grant funding is approximately $14 million. approximately $14 million.

Clinical trials may be awarded (in total costs Clinical trials may be awarded (in total costs (direct and indirect)) :(direct and indirect)) :

For Phase 1 Studies:For Phase 1 Studies: Up to $200,000 Up to $200,000 per year for up to 3 yearsper year for up to 3 years

For Phase 2 and 3 Studies:For Phase 2 and 3 Studies: Up to $400,000 Up to $400,000 per year for up to 4 years.per year for up to 4 years.

BudgetBudget

57

90 9296

105

87

4844

64

78

101

54

69

57 55 5765

92 94

125

15

28 2617 19 21 20

12 12 15 18 19 21 2217

1216

5 7 103

11 8 6 3 3 3 2 3 0 1 1 3 1 1 2 1

1220

16

0

20

40

60

80

100

120

140

'93 '94 '95 '96 '97 '98 '99 '00 '01 '02 '03 '04 '05 '06 '07 '08 '09 '10 '11 '12

Number of grant applications received

Number of new grants awarded

Number of competitive continuation grants awarded

Annual Number of OPD Grant Applications

Listing of past and currently funded grants:http://www.accessdata.fda.gov/scripts/opdlisting/oopdgrants/

Types of Products Supported by Active OPD Grants†

39%

6%

55%

Traditional drugsBiologicsMedical Device

† Excluding “no-cost extension” and supplemental grants

Composition of Orphan Grants

25% have a Phase 1 component25% have a Phase 1 component 55% have a Phase 2 component55% have a Phase 2 component 20% have a Phase 3 component20% have a Phase 3 component About 25% of funding goes to companiesAbout 25% of funding goes to companies About 50% are company/academic institution About 50% are company/academic institution

collaborationcollaboration

Overview Timeline FY 2014 Overview Timeline FY 2014 Grant ProgramGrant Program

Next Application receipt date - Next Application receipt date - February 6, 2013February 6, 2013 ((October 15, 2013October 15, 2013 will be a receipt date for resubmissions) will be a receipt date for resubmissions)

IDE IDE mustmust be be in effectin effect at time of the grant application at time of the grant application submission (IDE must be submission (IDE must be activeactive and include the and include the protocol for which funding is requested)protocol for which funding is requested) Protocol should be submitted to IDE by January 7, 2013 (earlier Protocol should be submitted to IDE by January 7, 2013 (earlier

if submitted with original IDE)if submitted with original IDE)

Application summary statement - ~August 2013Application summary statement - ~August 2013

Earliest start date for award - November 2013Earliest start date for award - November 2013

All FY 2014 funding completed by September 2014 All FY 2014 funding completed by September 2014

Grant Application ProcessGrant Application Process RegistrationsRegistrations

Request a DUNS numberRequest a DUNS number Register with CCR (Central Contractor Registration) Register with CCR (Central Contractor Registration) Register with Credential ProviderRegister with Credential Provider Register with Grants.govRegister with Grants.gov Register eRARegister eRA

Grant Application ProcessGrant Application Process Grants.govGrants.gov

Submit electronically through www.grants.gov Submit electronically through www.grants.gov Follow instructions under “Apply for Grants”Follow instructions under “Apply for Grants”

Search using RFA information (FD13-001)Search using RFA information (FD13-001) Download copy of application package (SF-424RR) and instructionsDownload copy of application package (SF-424RR) and instructions

““Applicant Help” section provides User’s Guide, FAQs and other Applicant Help” section provides User’s Guide, FAQs and other supportsupport

Complete offlineComplete offline Upload and submit via grants.gov web site Upload and submit via grants.gov web site Track status of application via grants.govTrack status of application via grants.gov

FOA link in NIH Guide at: FOA link in NIH Guide at: http://grants.nih.gov/grants/guide/rfa-files/RFA-FD-13-001.htmlhttp://grants.nih.gov/grants/guide/rfa-files/RFA-FD-13-001.html

Helpful hints available on OPD’s websiteHelpful hints available on OPD’s website

Review Process Primary Review: Grants scored by independent ad Primary Review: Grants scored by independent ad

hoc expert panels for technical merit hoc expert panels for technical merit Criteria are in the RFA Criteria are in the RFA

Funding based on scores (100-500 – lower scores are Funding based on scores (100-500 – lower scores are better)better)

The recent fundable range was 100-150The recent fundable range was 100-150 Medical Officer of IDE invited to participate in ad hoc Medical Officer of IDE invited to participate in ad hoc

panelpanel Summary Statements contain review specificsSummary Statements contain review specifics

Merit Criteria Ad hoc expert panel reviews application based on Ad hoc expert panel reviews application based on

the following scientific and technical merit criteria:the following scientific and technical merit criteria: Soundness of study rationale and designSoundness of study rationale and design Appropriateness of statistical powering and plans for results Appropriateness of statistical powering and plans for results

analysisanalysis Evidence that the proposed number of subjects can be recruited in Evidence that the proposed number of subjects can be recruited in

the requested timeframethe requested timeframe Qualifications of the investigator and support staff and availability Qualifications of the investigator and support staff and availability

of resourcesof resources Justification for financial support requestJustification for financial support request Adequacy of plans for protection of human subjects and study Adequacy of plans for protection of human subjects and study

monitoringmonitoring Ability of applicant to complete study within its budget and within Ability of applicant to complete study within its budget and within

the time limits of the grantthe time limits of the grant

Second Level review by a National Council Second Level review by a National Council (process approval) (process approval)

OPD Project Officer checks prefunding OPD Project Officer checks prefunding certifications prior to funding (check IRB, certifications prior to funding (check IRB, foreign sites, etc.)foreign sites, etc.)

Review Process

Responsibilities of Applicants Response to Summary Statement Critiques & Complete Response to Summary Statement Critiques & Complete

OOPD Pre-Certification Form OOPD Pre-Certification Form Maintain Regulatory requirements (IRB, FWA, IDE, Maintain Regulatory requirements (IRB, FWA, IDE,

Clinicaltrials.gov, GCP)Clinicaltrials.gov, GCP) Verify an adequate supply of study product is availableVerify an adequate supply of study product is available Set enrollment goalsSet enrollment goals Quarterly progress reports to the grantQuarterly progress reports to the grant

Publication of study results encouragedPublication of study results encouraged

Submit Type V Applications for following years with Submit Type V Applications for following years with Progress report Progress report

How OOPD interacts with Grantees PO is assigned grant, introduces to grantee and review PO is assigned grant, introduces to grantee and review

division RPMdivision RPM Establishes enrollment goals with granteeEstablishes enrollment goals with grantee Ensures regulatory requirements maintained (IDE ARs, IRB Ensures regulatory requirements maintained (IDE ARs, IRB

approvals, FWA, etc)approvals, FWA, etc) Evaluates progress and makes recommendations for Evaluates progress and makes recommendations for

continued fundingcontinued funding If issues with enrollment/study progress, PO will work with If issues with enrollment/study progress, PO will work with

grantee. Always defer to Review Division for any study grantee. Always defer to Review Division for any study changes suggested (inclusion criteria/exclusion changes suggested (inclusion criteria/exclusion criteria/age/patient numbers, etc)criteria/age/patient numbers, etc)

Future Years Support

Future years of noncompetitive continuation of Future years of noncompetitive continuation of support depends on: support depends on: Performance during the preceding year Performance during the preceding year Compliance with regulatory requirements of IDECompliance with regulatory requirements of IDE Availability of Federal fundsAvailability of Federal funds

Grants Statistics

To date, since 1983, FDA has provided To date, since 1983, FDA has provided more than $307 million for more than 500 more than $307 million for more than 500 grants for studies on rare diseases.grants for studies on rare diseases.

Current annual budget ≈ $14 million Current annual budget ≈ $14 million

>40 FDA approved products were at least >40 FDA approved products were at least partially funded through the OOPD Grants partially funded through the OOPD Grants Program.Program.

Approved Products Supported by Orphan Grants

Over 40 products partially funded by OOPD grants approved Over 40 products partially funded by OOPD grants approved for marketing for marketing

Examples: Examples: Elaprase Elaprase ®® (idursulfase): Enzyme replacement therapy (idursulfase): Enzyme replacement therapy for patients with MPS II for patients with MPS II

(Hunter Syndrome). (Hunter Syndrome). BabyBIGBabyBIG® ® (botulism immune globulin): infant botulism(botulism immune globulin): infant botulism TOBITOBI®® (tobramycin): cystic fibrosis (tobramycin): cystic fibrosis VEPTR™ (vertical expandable prosthetic titanium rib): thoracic insufficiency VEPTR™ (vertical expandable prosthetic titanium rib): thoracic insufficiency

syndromesyndrome Xiaflex (Collagenase): Dupuytren's Disease Xiaflex (Collagenase): Dupuytren's Disease Folotyn (Pralatrexate): Relapsed T-Cell non-Hodgkin’s lymphoma Folotyn (Pralatrexate): Relapsed T-Cell non-Hodgkin’s lymphoma Anascorp (Centruroides (Scorpion) Immune F(ab')2 (Equine) Injection): Anascorp (Centruroides (Scorpion) Immune F(ab')2 (Equine) Injection):

envenomation by poisonous scorpions in the USenvenomation by poisonous scorpions in the US

Funded StudiesFunded Studies

Search OOPD funded studies at:Search OOPD funded studies at:http://www.accessdata.fda.gov/scripts/opdlisting/oopdgrants/http://www.accessdata.fda.gov/scripts/opdlisting/oopdgrants/

Clinicaltrials.govClinicaltrials.gov

10 FDA Hints – Useful Homework10 FDA Hints – Useful Homework

1.1. Start early, plan carefully, write clearly, and Start early, plan carefully, write clearly, and objectivelyobjectively

2.2. Establish good relations w/ FDA review divisions via Establish good relations w/ FDA review divisions via IDE process. OPD invites FDA review divisions to the IDE process. OPD invites FDA review divisions to the review as a resource (FDA does not score the review as a resource (FDA does not score the application).application).

3.3. Read the RFA and instructions carefully not just for Read the RFA and instructions carefully not just for deadlines deadlines

4.4. Use the Grant Writing Tips from NIH Extramural Use the Grant Writing Tips from NIH Extramural Programs: http://grants.nih.gov/grants/grant_tips.htm Programs: http://grants.nih.gov/grants/grant_tips.htm

5.5. Call OPD for program clarifications – 301-796-8660Call OPD for program clarifications – 301-796-8660

10 FDA Hints – Useful Homework 10 FDA Hints – Useful Homework 6.6. Call Grants Management for budget help Call Grants Management for budget help

contact: Vieda Hubbard (301-827-7177)contact: Vieda Hubbard (301-827-7177)7.7. If you do not have expertise for issues, If you do not have expertise for issues,

provide letters of collaboration for the needed provide letters of collaboration for the needed expertiseexpertise

8.8. Panel Reviewers are busy, so say it in fewer Panel Reviewers are busy, so say it in fewer words if possiblewords if possible

9.9. Use outside readers improve the quality of the Use outside readers improve the quality of the proposal proposal

10.10. Don’t be discouraged – read summary Don’t be discouraged – read summary statements and address all critiquesstatements and address all critiques

Other Grant Opportunities FDA OPD Grant Program (R01)FDA OPD Grant Program (R01) Other Federally funded grantsOther Federally funded grants

Grants.gov- search under “find grant opportunities”Grants.gov- search under “find grant opportunities” Small business funding opportunities: Small business funding opportunities:

Small Business Innovation Research (SBIR) programSmall Business Innovation Research (SBIR) program Small Business Technology Transfer (STTR) ProgramSmall Business Technology Transfer (STTR) Program

Patient Advocacy Groups Patient Advocacy Groups NORD’s Research Grant ProgramNORD’s Research Grant Program

Small grants to academic scientists studying new treatments or diagnostics for rare Small grants to academic scientists studying new treatments or diagnostics for rare diseases. (www.rarediseases.org)diseases. (www.rarediseases.org)

Disease Specific/Patient Advocacy GroupsDisease Specific/Patient Advocacy Groups International Rare Disease Research Consortium International Rare Disease Research Consortium

((IRDiRC)IRDiRC) Global effort to deliver 200 new therapies for patients with rare diseases by Global effort to deliver 200 new therapies for patients with rare diseases by

20202020

Contact:Contact:Katherine Needleman Katherine Needleman

Director of Orphan Products Grants ProgramDirector of Orphan Products Grants Program

((Katherine.Needleman@fda.hhs.govKatherine.Needleman@fda.hhs.gov) )

*For more information, go to OOPD’s website*For more information, go to OOPD’s website

http://www.fda.gov/ForIndustry/DevelopingProductsforRareDiseasesConditions/WhomtoConhttp://www.fda.gov/ForIndustry/DevelopingProductsforRareDiseasesConditions/WhomtoContactaboutOrphanProductDevelopment/default.htmtactaboutOrphanProductDevelopment/default.htm

Orphan Products Grants ProgramOrphan Products Grants Program

OOPD Website http://www.fda.gov/orphan http://www.fda.gov/orphan

Your Link to:Your Link to: Overview of FDA Office of Orphan Products Overview of FDA Office of Orphan Products

DevelopmentDevelopment Guidelines for designation applicationGuidelines for designation application List of designated and approved orphan productsList of designated and approved orphan products Grant application informationGrant application information List of ongoing orphan grant studiesList of ongoing orphan grant studies Contact information for OOPD staff Contact information for OOPD staff

Main Telephone # is (301) 796-8660Main Telephone # is (301) 796-8660

Thank You!Thank You!