Introduction

As announced in the Federal Register notice published on October 27, 2022, FDA is establishing a Rare Disease Endpoint Advancement (RDEA) Pilot Program to support novel endpoint efficacy development for drugs that treat rare diseases. The RDEA Pilot Program fulfills a commitment under PDUFA VII.

Goals of the RDEA Pilot Program

The RDEA Pilot Program is designed to:

• Seek to advance rare disease drug development programs by providing a mechanism for sponsors to collaborate with FDA throughout the efficacy endpoint development process.
• Promote innovation and evolving science by sharing learnings on novel endpoint development through FDA presentations, guidance documents, public workshops, and a public-facing website.
• Develop FDA staff capacity to enable and facilitate the development and use of novel endpoints to evaluate the efficacy of rare disease therapies.

General Program, Procedures, and Submission Information

The RDEA Pilot Program is a joint program of the Center for Drug Evaluation and Research and the Center for Biologics Evaluation and Research. 

Under the pilot program, sponsors may begin submitting RDEA program proposal requests (RDEA proposals) in the fourth quarter of fiscal year 2023 (July 1, 2023, through September 30, 2023), and FDA will accept 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 RDEA proposals per year. For each RDEA proposal that FDA admits into the pilot program, the agency will conduct an initial meeting and, if requested, up to three follow-up meetings.

Before FDA grants the initial meeting under the RDEA Pilot Program, the Agency and the sponsor must agree on the information that FDA may disclose publicly.  After a sponsor is admitted into the RDEA pilot program, each RDEA meeting will be scheduled within 45 days following FDA’s receipt of the sponsor’s meeting request and complete meeting package.

FDA advice provided during the RDEA program should not be equated with a special protocol assessment or agreement that the proposed approach is sufficient to support approval of a marketing submission.

RDEA Proposal Eligibility Criteria

• Sponsor has an active pre-IND or IND for a rare disease
  • Exceptions
    • Sponsors who do not yet have an active development program but have, or are initiating, a natural history study where the proposed endpoint is intended to be studied are also eligible.
    • The FDA may also consider accepting a proposal for a development program for a common disease that includes innovative or novel endpoint elements, including the specific endpoint and/or the methodology being developed, if there is sufficient justification that the proposal could be applicable to a rare disease
• The proposed endpoint is a novel efficacy endpoint intended to establish substantial evidence of effectiveness for a rare disease treatment.
  • An endpoint is considered 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.

RDEA Proposal Selection

FDA welcomes RDEA proposals related to any eligible novel endpoint for a rare disease. However, given that FDA expects to admit a limited number of RDEA proposals into the pilot program, the agency will give preference to proposals that:

• Have the potential to impact drug development more broadly, such as one that uses a novel approach to develop an efficacy endpoint or an endpoint that could potentially be relevant to other diseases.
• Reflect/impact a range of different types of endpoints.
• For surrogate endpoints, those that use novel approaches for collecting additional clinical data in the pre-market stage to advance the validation of these endpoints. (If the 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.)

FDA will notify the sponsor with a final selection decision no later than 60 days following the end of the fiscal year quarter during which the RDEA proposal is submitted.

Submission Deadlines and Process

Content and Format of the RDEA Proposal

RDEA Pilot Program Disclosure Agreement

Content and Format of the RDEA Meeting Request and Package

Frequently Asked Questions

Visit Rare Disease Endpoint Advancement Pilot Program Frequently Asked Questions for more information about the program.

For more information about the RDEA Program

• FDA CDER and CBER & Duke-Margolis Center for Health Policy | Rare Disease Endpoint Advancement Pilot Program Workshop: Novel Endpoints for Rare Disease Drug Development, JUNE 7 - 8, 2023

RDEA Contact Information:  RDEA.Meetings@fda.hhs.gov