Rett Syndrome Gene Therapy Adds RMAT Designation to the List
NGN-401 is being evaluated in an early phase clinical trial which has been selected for the FDA’s START Pilot Program.
Rachel McMinn, PhD
Credit: Neurogene
The FDA has granted Regenerative Medicine Advanced Therapeutic Designation to Neurogene’s gene therapy NGN-401 for the potential treatment of Rett syndrome.1
“We appreciate the FDA’s ongoing commitment to expedite development of our NGN-401 gene therapy for Rett syndrome, with RMAT designation following NGN-401’s selection for the FDA’s START Pilot Program, 2 synergistic initiatives designed to more rapidly advance promising treatments for patients with unmet medical needs,” Rachel McMinn, PhD, Founder and Chief Executive Officer, Neurogene, said in a statement.1 “RMAT and START designations underscore the therapeutic potential of NGN-401 for Rett syndrome and reflect our commitment to accelerate development of NGN-401. We continue to expect to share interim efficacy data from the low-dose cohort in the fourth quarter of this year, with plans for additional data, including from the high-dose cohort, in the second half of 2025.”
NGN-401 is an investigational adeno-associated virus (AAV9) gene therapy that delivers the full-length human MECP2 gene using Neurogene’s EXACT technology. The EXACT technology is designed to enable targeted levels of MECP2 transgene expression without causing overexpression-related toxic effects seen with other AAV gene therapies. NGN-401 has previously received orphan drug designation, Fast Track designation and rare pediatric designation from the FDA, orphan designation and advanced therapy medicinal product designation from the European Medicines Agency (EMA), and the Innovative Licensing and Application Pathway (ILAP) designation from the United Kingdom (UK) Medicines and Healthcare products Regulatory Agency (MHRA).
Neurogene also announced in June 2024 that NGN-401 had been selected as part of the FDA’s Support for Clinical Trials Advancing Rare Disease Therapeutics (START) Pilot Program.2 The program will provide sponsors with the opportunity for frequent advice and regular communication as needed with regard to clinical trial design and other development issues particular to the investigational product being evaluated.
“We are honored that NGN-401 gene therapy for Rett syndrome has been chosen as one of only 3 CBER programs for FDA’s START Pilot Program and are grateful that the FDA has committed to investing significant Agency resources to accelerate development of NGN-401,” McMinn said in an earlier statement.2 “We are pleased our application demonstrated the potential clinical benefits of NGN-401, 1 of the factors evaluated by the FDA in making its selection. We look forward to participating in this landmark effort with the FDA as we seek to rapidly advance NGN-401 toward a potential registrational study for the patients and families who live with this devastating disease.”
NGN-401 is being evaluated in a phase 1/2 clinical trial (NCT05898620). As of June 2024, the therapy has been well-tolerated in treated study participants, with all treatment-related adverse events (AEs) being mild and transient or resolving. There have been no signs of MeCP2 overexpression toxicity, including in a patient with a mild genetic variant predicted to result in residual MeCP2 expression. There have also been no treatment-emergent or intracerebroventricular (ICV) procedure-related serious AEs.3
“We have met an important program milestone of initiating dosing in the high-dose cohort of our Rett syndrome gene therapy trial, and we are pleased to share that high-dose NGN-401 has been well-tolerated thus far with an early favorable safety profile,” McMinn said in a statement at that time.3 “We intentionally designed NGN-401 with the goal of creating a best-in-class treatment option by leveraging what we believe to be the optimal route of administration to deliver consistent and tightly controlled full-length MECP2 expression to key areas of the brain and nervous system, and today’s safety update underscores NGN-401’s potential to deliver on that profile. We remain on track to share interim efficacy data from the low-dose cohort in the fourth quarter of 2024 and look forward to working with the FDA as part of its START Pilot Program to accelerate the development of NGN-401.”
