The FDA announced the Rare Disease Evidence Principles (RDEP) program, a new review pathway designed to facilitate the development and approval of drugs targeting ultra-rare genetic diseases affecting fewer than 1,000 individuals in the U.S. This initiative allows for flexible evidence standards, including acceptance of single-arm clinical trials, natural history data, and case reports as sufficient for demonstrating substantial evidence of effectiveness. The program reflects continued efforts to expedite therapies for underserved patient populations by accommodating the challenges inherent in studying ultra-rare disorders.