Reissue of RFA-FD-23-001- Clinical Studies of Orphan Products Addressing Unmet Needs of Rare Diseases (R01 Clinical Trials Required)

The U.S. Food and Drug Administration (FDA), through its Office of Orphan Products Development (OOPD), has reissued its funding opportunity RFA-FD-25-020 under the Research Project Grant (R01) mechanism. The purpose of this funding opportunity is to support clinical trials evaluating the efficacy and/or safety of medical products for new indications or changes in labeling to address the unmet medical needs of individuals with rare diseases or conditions. This initiative aims to expand the number of approved treatments for rare diseases through the funding of collaborative, efficient, and innovative clinical trials. The FDA defines a rare disease or condition as one that affects fewer than 200,000 people in the United States. This definition applies to both chronic diseases based on prevalence and acute conditions based on annual incidence. The grant supports all phases of clinical development—phases 1, 2, and 3—and encourages trial designs that are seamless, adaptive, basket, umbrella, or platform-based, as well as the use of innovative data modeling and simulation methods. Projects that integrate early and continuous patient input and leverage established infrastructure, such as clinical trial networks and data sharing platforms, are particularly encouraged. The award provides up to $650,000 annually in total costs (direct and indirect) for up to four years. Projects proposing innovative clinical trial methods may apply for up to $900,000 per year, contingent upon adequate justification. Funding for years two through four is subject to annual appropriations, satisfactory performance, and regulatory compliance. No cost-sharing or matching is required for eligibility. The grant is open to a wide range of applicants, including public and private higher education institutions, non-profits, small and large businesses, state and local governments, tribal organizations, foreign institutions, and more. Individual principal investigators with the appropriate experience and institutional support may also apply. All applicants must be registered in SAM, Grants.gov, eRA Commons, and have a Unique Entity Identifier (UEI). Principal Investigators must also be registered in eRA Commons. The application process includes optional Letters of Intent due on September 22, 2025; September 21, 2026; and September 20, 2027. Full applications are due October 21, 2025; October 20, 2026; and October 19, 2027, with resubmission deadlines in May of the following years. The earliest possible award start date is July 2026. Applications must be submitted electronically via ASSIST, Grants.gov Workspace, or an institutional system-to-system solution, and must be free of submission errors by 11:59 PM Eastern Time on the deadline. Scientific merit reviews for new applications are scheduled for February/March in 2026, 2027, and 2028, and for resubmissions in June of those same years. Applications will be reviewed on criteria such as study rationale, trial design, inclusion of patient input, investigator qualifications, and the potential for the study to advance the field. The final funding decisions will be made by the Commissioner of Food and Drugs or a designated representative. Contact for scientific and research questions is Katherine Needleman, Director of the Orphan Products Grants Program, at OOPD_CTGrants@fda.hhs.gov or 301-796-8660.

Early contact with FDA review divisions is recommended; Ensure IND/IDE submission 30 days prior to applying.