FDA Unveils Rare Disease Therapy Approval Process

The FDA has introduced the Rare Disease Evidence Principles (RDEP) to speed up the review of therapies for rare diseases with small patient populations. The RDEP process provides clearer guidance on the types of evidence needed for approval, including single-arm trials and alternative data sources. This may benefit companies developing gene therapies, such as Neurogene Inc. and Rocket Pharmaceuticals Inc. However, the impact of the framework on the development process and approval timeline is unclear.

The Food and Drug Administration (FDA) has unveiled the Rare Disease Evidence Principles (RDEP), a new framework designed to expedite the review process for therapies targeting rare diseases with small patient populations. The initiative, announced on September 4, 2025, aims to provide clearer guidance on the types of evidence required for drug approval, including single-arm trials and alternative data sources.

Under the RDEP, the FDA will work more closely with developers of drugs for ultra-rare conditions, coordinating efforts between the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER). The new process accepts evidence from single-arm clinical trials, case reports, and natural history studies as sufficient for meeting the agency's threshold for "substantial evidence of effectiveness."

The RDEP program follows Commissioner Marty Makary's promise to expedite the development and review of rare disease medicines. It also builds on years of work at the FDA, including 2023 guidance that outlines how companies should demonstrate sufficient supportive evidence with one primary clinical trial. Peter Marks, who led CBER until his ouster this spring, had also pushed for more flexible standards for cell and gene therapies that treat rare diseases.

To qualify for the RDEP program, prospective applicants must treat a disease driven by a known genetic defect and affecting fewer than 1,000 people in the U.S. The target condition must lead to progressive deterioration in an individual's functioning, causing significant disability or death within a short period. Additionally, there must be no adequate alternative therapies that change the disease's trajectory.

Once accepted, drugmakers will meet with the FDA to discuss study designs and needed supporting evidence. The process could also include patient listening sessions. Applications will be reviewed by CBER and CDER teams, who will consult with a coordinating Rare Disease Policy and Portfolio Council.

The impact of the RDEP on the development process and approval timeline remains unclear. Analysts note that companies like Neurogene, Rocket Pharmaceuticals, Ultragenyx, and UniQure plan to use single-arm studies to support approval applications for gene therapies they're developing. However, most therapies in development may not be eligible due to the patient size restriction.

Walden Biosciences, a private biotechnology company, has also announced key initiatives to support its rare kidney disease drug development program, WAL0921. The company has engaged a leading regulatory advisor, Norman Stockbridge, M.D., Ph.D., and a patient advocacy group, NephCure, to broaden awareness and support patient recruitment for its ongoing Phase 2 clinical study.

References:
[1] https://www.biopharmadive.com/news/fda-rare-disease-evidence-principles-drug-reviews/759237/
[2] https://www.globenewswire.com/news-release/2025/09/04/3144313/0/en/Walden-Biosciences-Announces-Key-Initiatives-to-Advance-Clinical-Pipeline-and-Support-Phase-2-Program-for-WAL0921-in-Rare-Kidney-Diseases.html