FDA Launches New Streamlined Review Pathway for Ultra-Rare Disease Drugs

The U.S. Food and Drug Administration (FDA) has introduced the Rare Disease Evidence Principles (RDEP) framework to streamline the approval process for drugs targeting ultra-rare genetic diseases affecting fewer than 1,000 people in the U.S. This new pathway allows drug sponsors to rely on a single well-controlled trial, potentially a single-arm study, supported by other confirmatory evidence such as clinical pharmacodynamic data, non-clinical models, and case reports, to establish substantial evidence of effectiveness. Eligibility criteria are strict, requiring that the drug targets a genetic defect driving a rapidly progressing disease with no existing adequate therapies. FDA Commissioner Marty Makary emphasized the agency's commitment to a flexible yet rigorous review process incorporating expert and patient input. While some analysts and rare disease advocates criticize the framework as largely reiterating current practices and question its tangible impact, others view it as a positive signal of a more favorable regulatory environment for rare disease drug development. Overall, the RDEP aims to address the unique challenges in rare disease clinical development and accelerate patient access to novel therapies.