RFA-FD-25-020
Reissue of RFA-FD-23-001- Clinical Studies of Orphan Products Addressing Unmet Needs of Rare Diseases (R01 Clinical Trials Required)
Summary
RFA-FD-25-020: Clinical Studies of Orphan Products for Rare Diseases
Research Focus
This funding opportunity supports clinical trials of orphan products (drugs, biologics, medical devices, medical foods) in phases 1, 2, and/or 3 for rare diseases affecting fewer than 200,000 people in the U.S. (or with annual incidence below 200,000 for acute conditions). Trials must evaluate safety and/or efficacy to support a new indication or labeling change addressing unmet medical needs. The FDA Office of Orphan Products Development seeks to increase approved treatments for rare diseases—currently only a few hundred of over 10,000 rare diseases have approved therapies despite affecting ~30 million Americans. Applicants are encouraged to use established clinical trial networks, standardized data platforms, collaborative stakeholder partnerships (industry, academia, patient organizations), and early patient engagement in trial design. Applications proposing innovative trial designs (seamless, adaptive, basket, umbrella, platform trials) or data modeling and simulation methods are eligible for additional funding.
At a Glance
- Who can apply: Higher education institutions, nonprofits, for-profit organizations, state/local governments, tribal governments, foreign organizations, and other entity types. Domestic and non-domestic components eligible.
- Funding & project length: $650,000/year (years 1–4); up to $900,000/year with justification for innovative trial approaches. Maximum 4-year project period.
- Award mechanism: R01 Research Project Grant; clinical trials required.
- Key dates: LOI optional September 22, 2025; applications due October 21, 2025 (11:59 PM ET); scientific merit review February/March 2026; earliest start July 2026. Resubmission deadlines: May 19, 2026 and beyond.
- Best fit for: Rare disease drug development teams conducting phase 1–3 clinical trials with focus on safety/efficacy, particularly those using adaptive designs, patient-centered outcomes, or collaborative trial infrastructure.
Key Facts
Deadline
Tue, May 16, 2028
Posted
Fri, July 11, 2025
Award / Year (total costs)
$650,000
Max Total
$2,600,000
Max Duration
4 years
Keywords
Research Areas
Gotchas (7)
FDA does not follow NIH Page Limitation Guidelines or NIH Review Criteria; applicants must consult with FDA Agency Contacts for page limits and review process details
95%
Source Text
“The FDA does not follow the NIH Page Limitation Guidelines or the NIH Review Criteria. Applicants are encouraged to consult with FDA Agency Contacts for additional information regarding page limits and the FDA Objective Review Process.”
Resubmission applications have different due dates (May 19, 2026; May 18, 2027; May 16, 2028) than new applications (October dates), with strict eligibility requirements for resubmissions
90%
Source Text
“Resubmissions ONLY Application Due Date(s): May 19, 2026; May 18, 2027; May 16, 2028 by 11:59 PM Eastern Time. See resubmission eligibility requirement below.”
Applications must be submitted error-free in both Grants.gov and eRA Commons by deadline; on-time submission requires error-free submission
90%
Source Text
“Applicants should be aware that on-time submission means that an application is submitted error free (of both Grants.gov and eRA Commons errors) by 11:59 PM Eastern Time on the application due date. No late applications will be accepted for this Notice of Funding Opportunity (NOFO).”
Clinical trials are REQUIRED for this RFA; only applications proposing clinical trial(s) will be accepted
95%
Source Text
“Clinical Trial? Required: Only accepting applications that propose clinical trial(s).”
Continuation funding for years 2-4 is contingent on annual appropriations, satisfactory performance, and regulatory compliance; not guaranteed
95%
Source Text
“Award(s) will provide one (1) year of support and include future recommended support for an additional three (3) years contingent upon annual appropriations, availability of funding, and satisfactory recipient performance. For those studies with an expected duration of more than 1 year, a second, third, or fourth year of noncompetitive continuation of support will depend on the following factors: (1) Performance during the preceding year; (2) compliance with regulatory requirements of IND/invest”
Policies, guidelines, terms, and conditions in this NOFO may differ from NIH guidance; where NOFO provides specific written guidance differing from general guidance in grant application form, follow N
85%
Source Text
“NOTE: The policies, guidelines, terms, and conditions stated in this Notice of Funding Opportunity (NOFO) may differ from those used by the NIH. Where this NOFO provides specific written guidance that may differ from the general guidance provided in the grant application form, please follow the instructions given in this NOFO.”
Additional funding up to $250,000/year (max $900,000/year total) available for innovative trial designs, but justification must be in budget request and reviewed annually
90%
Source Text
“Applicants may request additional funding over the above listed maximums for innovative and efficient trial approaches. The additional funding request shall not exceed an additional $250,000 total costs per year (to a maximum total award cost of $900,000 per year) for up to 4 years. Justification for the additional funding request must be reflected in the budget request and will be reviewed annually by the program.”