FDA Approves Pivotal Study Design for Neurogene's Rett Syndrome Gene Therapy

Neurogene has received FDA approval for the design of a registrational study for its investigational gene therapy NGN-401, aimed at treating Rett Syndrome. This development allows the biotech company to convert its current Phase I/II study into a pivotal trial, marking a significant step forward in the treatment of this rare genetic disorder.

Study Design and Endpoint

The FDA-approved study design features a single-arm, baseline-controlled trial involving female patients aged three years and older. NGN-401 will be administered as a single dose, with the primary endpoint assessing treatment responders using the Clinical Global Impression-Improvement (CGI-I) scale and the achievement of developmental milestones or skills.

Analysts from William Blair consider this agreement with the FDA as the "best-case scenario" for Neurogene, praising the "favorable/feasible control strategy, rigorous primary endpoint, and broad age range." The endpoint's stringent definition of a treatment responder is expected to be beneficial for future labeling and payer discussions, should the therapy receive approval.

Comparison with Competitors

Neurogene's study design has drawn comparisons to that of Taysha Gene Therapies, which recently reached a similar agreement with the FDA for its Rett syndrome gene therapy, TSHA-102. While the studies share similarities, key differences exist in the age range of participants and the definition of treatment responders.

Analysts from Stifel noted that Neurogene intentionally chose a more rigorous endpoint "for the broadest label," which could provide a significant commercial advantage. This decision aligns with Neurogene's strategy to potentially secure a more comprehensive label for NGN-401, if approved.

Regulatory Context and Future Implications

The FDA's approval of Neurogene's study design comes amid signals from the agency's new leadership indicating support for regulatory flexibility in gene therapies and rare diseases. FDA Commissioner Marty Makary has expressed openness to considering a new pathway for approving rare disease therapies based on a candidate's "plausible mechanism."

Vinay Prasad, director of the Center for Biologics Evaluation and Research, has also emphasized the agency's commitment to rapidly making treatments available for rare diseases by allowing flexibility in regulatory requirements, such as the use of novel endpoints.

This regulatory environment, coupled with Neurogene's successful alignment with the FDA on its pivotal study design, suggests a potentially smoother path forward for innovative gene therapies targeting rare genetic disorders like Rett Syndrome.