FDA Issues Draft Guidance Establishing Framework for Individualized Gene Therapies

The  Food and Drug Administration issued draft guidance on Monday outlining a new regulatory framework for generating substantial evidence of effectiveness and safety for individualized gene and RNA-based therapies for ultra-rare diseases. The “plausible mechanism” framework aims to support approval of these individualized therapies when randomized controlled trials are not feasible due to small patient populations.

Under the framework, sponsors must identify a specific genetic, cellular or molecular abnormality with a clear connection between specific alteration and disease indication. Sponsors must also develop a therapy that directly targets the underlying or proximate pathogenic biological alterations. The guidance further recommends relying on well-characterized natural history data in untreated patients, confirmation that the target has been successfully drugged or edited, and demonstration of improvement in clinical outcomes or disease course.

The draft guidance clarifies that data generated under this approach may be sufficient to support approval or licensure under existing regulatory pathways. The agency emphasized that sufficient nonclinical, clinical and chemistry, manufacturing and controls (CMC) data are required to demonstrate product safety, effectiveness and quality.

FDA is accepting comments on the draft guidance through April 27. Instructions are available in the Federal Register notice.