The U.S. Food and Drug Administration (FDA) is accepting applications until June 30, 2026, for the Rare Disease Endpoint Advancement Pilot Program, an initiative designed to support the development of novel efficacy endpoints for drugs intended to treat rare diseases.
The program reflects a growing need in rare disease drug development: many conditions affect small patient populations, have limited natural history data, and lack established clinical endpoints that can reliably demonstrate treatment benefit. Through the RDEA Pilot Program, FDA aims to work more closely with sponsors as they develop endpoints that may help support future regulatory decision-making.
A Focused Pathway for Novel Endpoint Development
The RDEA Pilot Program was established following the Federal Register notice published on October 27, 2022, and fulfills a commitment under PDUFA VII. It is a joint effort of FDA’s Center for Drug Evaluation and Research and Center for Biologics Evaluation and Research.
The program is intended to provide sponsors with a structured opportunity to engage with FDA throughout the efficacy endpoint development process. For rare diseases, where traditional clinical trial designs and endpoints may not always be practical, this type of early and focused dialogue can be especially important.
Why the Program Matters for Rare Disease Research
Rare disease drug development often faces a difficult evidence-generation landscape. Patient populations may be very small, disease progression may vary widely, and validated outcome measures may not exist. In this setting, novel endpoints can play an important role in helping sponsors measure whether a treatment provides meaningful clinical benefit.
The RDEA Pilot Program is designed to support innovation in this area while also helping FDA build experience with new endpoint approaches. The program is not only intended to support individual development programs, but also to generate broader learning that may inform future rare disease research.
FDA has stated that learnings from the program may be shared through presentations, guidance documents, public workshops, and a public-facing website.
How the RDEA Pilot Program Works
Under the pilot program, sponsors may submit RDEA program proposal requests for consideration. In the fourth quarter of fiscal year 2023, FDA accepted a maximum of one RDEA proposal. For fiscal years 2024 through 2027, FDA will accept up to one RDEA proposal per quarter, with a maximum of three proposals per year.
For each proposal admitted into the pilot program, FDA will conduct an initial meeting. Sponsors may also request up to three follow-up meetings.
Each RDEA meeting will be scheduled within 45 days after FDA receives the sponsor’s meeting request and complete meeting package. Before the initial meeting is granted, FDA and the sponsor must agree on what information may be publicly disclosed.
Who Is Eligible to Apply?
To be eligible for the RDEA Pilot Program, sponsors must generally have an active pre-IND or IND for a rare disease. However, FDA has outlined exceptions.
Sponsors who do not yet have an active development program may still be eligible if they have, or are initiating, a natural history study where the proposed endpoint is intended to be studied.
FDA may also consider a proposal for a common disease development program if it includes innovative or novel endpoint elements and there is sufficient justification that the proposal could be applicable to a rare disease.
The proposed endpoint must be a novel efficacy endpoint intended to establish substantial evidence of effectiveness for a rare disease treatment. FDA considers an endpoint novel if it has never been used to support drug approval or if it has been substantially modified from previous use to support drug approval.
What FDA Will Prioritize
FDA welcomes RDEA proposals related to any eligible novel endpoint for a rare disease. However, because only a limited number of proposals will be admitted, the agency will give preference to proposals with broader potential impact.
Priority may be given to proposals that use a novel approach to develop an efficacy endpoint or propose an endpoint that could be relevant to other diseases. FDA will also consider whether proposals reflect or impact a range of different endpoint types.
For surrogate endpoints, FDA will give preference to proposals that use novel approaches for collecting additional clinical data in the pre-market stage to advance endpoint validation. If a sponsor is proposing to develop a surrogate endpoint as part of a rare disease application, participation in a prior Type C Surrogate Endpoint meeting is encouraged.
Selection Timeline
FDA will notify sponsors of the final selection decision no later than 60 days after the end of the fiscal year quarter during which the RDEA proposal is submitted.
This timeline gives sponsors a defined expectation for when they may learn whether their proposal has been admitted into the pilot program.
Important Regulatory Consideration
FDA has emphasized that advice provided through the RDEA Pilot Program should not be interpreted as a special protocol assessment or as an agreement that the proposed endpoint approach will be sufficient to support approval of a marketing application.
The program is intended to support endpoint development and regulatory dialogue, but it does not replace the full evidentiary standards required for drug approval.
Application Information
Sponsors interested in participating should review FDA’s submission deadlines and process, including requirements related to the content and format of the RDEA proposal, the RDEA Pilot Program disclosure agreement, and the content and format of the RDEA meeting request and package.
Additional information is available through FDA’s Rare Disease Endpoint Advancement Pilot Program Frequently Asked Questions.
A Step Toward Stronger Rare Disease Drug Development
The RDEA Pilot Program represents an important opportunity for sponsors developing rare disease therapies to engage with FDA on one of the most complex parts of clinical development: defining how treatment benefit should be measured.
As rare disease research continues to move forward, the development of scientifically sound, clinically meaningful, and fit-for-purpose endpoints will remain essential. Through this pilot program, FDA aims to support that progress while strengthening the broader regulatory framework for evaluating rare disease therapies.
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Written by Nare Hovhannisyan, MD