FDA罕见病证据原则（RDEP）

Report Summary 1. Report Industry Investment Rating - Not provided in the content. 2. Core Viewpoints - The RDEP represents a significant evolution in FDA's approach to ultra - rare disease drug development, emphasizing scientific flexibility and innovation while maintaining strict evidence standards [22]. - Success under the RDEP depends on strategic integration of real - world evidence, strong confirmatory evidence, and careful cooperation with regulatory agencies [24]. 3. Summary by Related Catalog RDEP Introduction - In September 2025, the FDA released the Rare Disease Evidence Principles (RDEP), a new review process for ultra - rare, genetically - defined diseases, aiming to provide more clarity and predictability [3]. - RDEP is built on the precedent of the FDA's 2023 draft guidance, using a well - controlled clinical study to prove effectiveness and provide confirmatory evidence [4]. Comparison with Existing Pathways - RDEP formalizes the FDA's previous practices in rare - disease approvals, and it supplements existing mechanisms like accelerated approval, orphan drug designation, and RDEA pilot by clarifying evidence expectations [7][8]. Eligibility for RDEP - RDEP aims to support therapy developers for diseases that meet all of the following conditions: a sponsor can prove a well - controlled study with strong evidence to establish effectiveness; the disease is caused by a known congenital genetic defect; the situation is critical, rapidly progressing, and there is no disease - modifying treatment; and fewer than 1000 patients in the US are affected [8]. Role of RWE - Before accessing the RDEP process, RWE can be used to confirm the ultra - rare prevalence threshold of a disease by combining medical claims, EHRs, genomic databases, and patient registries, and AI - driven analysis can further refine these estimates [11][12]. - Once in the RDEP process, RWE plays a core role in natural history studies, patient registries, external comparator arms, and expanded access data and case reports [15]. Patient - Centered Development - In ultra - rare diseases, patient - centered drug development is crucial, and natural history studies and registries, especially those co - designed with advocacy groups, help identify important functional changes for patients and caregivers [18]. Time Considerations - Before starting a critical trial, sponsors should submit an application to their existing IND for each protocol they want to be reviewed under RDEP, including reasonable evidence to meet the inclusion criteria and prove the drug's safety and effectiveness [21]. Conclusion - RDEP provides a customized pathway for programs less likely to meet traditional requirements, and cooperation is key to accelerating treatment for patients in need [23][24].