Snapshot

The Rare Disease Evidence Principles (RDEP) pathway has been developed by the of United States.

This pathway can be used where drugs to treat rare diseases with very small patient populations with significant unmet medical need and with a known genetic defect that is the major driver of the pathophysiology. .

This pathway accelerates the regulatory review process.

It is an abridged review (a reliance pathway).

Target time assessment is A. PROPOSED PROCESS. FDA expects that substantial evidence of effectiveness may generally be established based on one adequate and well-controlled study that may be a single arm trial, together with robust data that provides strong confirmatory evidence of the drug’s treatment effect. Such data may include: - evidence of the drug’s treatment effect on the direct pathophysiology of the disease; - evidence from a relevant non-clinical model; - therapeutically relevant clinical pharmacodynamic data; and - other clinical data including case reports and expanded access data. FDA will also consider confirmatory evidence provided through the appropriate selection of external controls or natural history studies. A determination of substantial evidence of effectiveness based upon one adequate and well-controlled study with confirmatory evidence may be found in some circumstances as described in the "Draft Guidance for Industry: Demonstrating Substantial Evidence of Effectiveness With One Adequate and Well-Controlled Clinical Investigation and Confirmatory Evidence (September 2023)".  B. REVIEW PROCESS. A request should be submitted to a sponsor’s existing investigational new drug (IND) prior to the launch of a pivotal trial for each protocol the sponsor wants reviewed under the RDEP; the request should include reasonable evidence that the eligibility criteria are met and that the safety and efficacy of the drug can be demonstrated by one adequate and well-controlled study with confirmatory evidence. A request for participation in this process should be accompanied by a formal meeting request appropriate for the sponsor’s stage in the drug development process. A request should not include more than one protocol. If there is no IND for the product, FDA will assign a pre-IND number so that a meeting can be scheduled to fully inform FDA of the overall development plan for the product. The sponsor can subsequently open an IND after the meeting and then submit a request to the IND. The relevant center review team would issue a decision on acceptance following a consultation with the CDER/CBER RDPPC. Accepted sponsors will have an initial meeting with the appropriate FDA review team to determine what data will be used to substantiate safety and effectiveness. The Agency’s concurrence on study design and qualifying confirmatory evidence would not necessarily indicate that the Agency expects to determine that the drug is approvable. FDA and sponsors would be encouraged to incorporate patient experience data, including by leveraging separate patient listening sessions where appropriate. At this initial meeting, the agency and the sponsor may discuss the need for future engagement at significant milestones in the drug development and/or application process, touchpoints between the agency and the sponsor at critical points of determining relevant evidence, etc. .