The FDA has introduced a new submission and review pathway for gene therapies targeting ultra-rare diseases, coordinated by its Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER)1.
The program, described as the Rare Disease Endpoint Advancement (RDEP) Pilot, allows drugs for ultra-rare diseases (affecting fewer than 1,000 people in the U.S. and caused by a known genetic defect) to be approved with just one adequate and well-controlled study, if supported by strong confirmatory evidence from sources such as non-clinical models, pharmacodynamic studies, case reports, or natural history studies1.
Prospective applicants must apply before starting their main supporting study. Acceptable applications will be reviewed by specialized teams from both CDER and CBER who consult with a new Rare Disease Policy and Portfolio Council1.
The program emphasizes increased communication between sponsors and the FDA, including opportunities for stakeholder and patient input during the study design and evidence collection phases14.
CBER continues to prioritize gene therapies for rare diseases, with an accelerated rate of approvals and ongoing publication of guidance documents to facilitate the development and regulatory review of cell and gene therapies23.
Recently, CBER doubled its approval rate for cell and gene therapies for rare diseases, reflecting a strategic push in this area after its internal reorganization in 20232.
The FDA is expected to release new guidance on 'Accelerated Approval of Human Gene Therapy Products for Rare Diseases,' potentially expanding regulatory flexibility for such therapies with defined endpoints or surrogate markers3.
Industry analysts note that while the program demonstrates FDA's increased flexibility, the full impact on development timelines and approval rates remains to be seen1.
Sources:
1. https://www.biopharmadive.com/news/fda-rare-disease-evidence-principles-drug-reviews/759237/
2. https://www.aabb.org/news-resources/news/article/2025/01/27/cber-director-s-report-highlights-advances-in-cellular-and-gene-therapy--transfusion-medicine
3. https://www.cellandgene.com/doc/cell-gene-therapies-will-represent-a-continuation-of-fda-s-developments-0001
4. https://www.bstquarterly.com/article/how-fda-is-working-to-accelerate-rare-disease-treatments/