NEW YORK – A patient with Rett syndrome who had received Neurogene's investigational gene therapy NGN-401 in an ongoing clinical trial has died, the company disclosed in a recent submission to the US Securities and Exchange Commission.
New York-based Neurogene earlier this month disclosed that a patient treated with NGN-401 on Nov. 5 within the open-label single-arm Phase I/II trial was in critical condition. Then, last week, the firm told the SEC that the patient had died from complications linked to a rare and life-threatening hyperinflammatory syndrome associated with systemic exposure to high doses of adeno-associated virus (AAV), the mechanism used to deliver the gene therapy in the body.
NGN-401 uses an AAV serotype 9 vector to deliver a full-length copy of the MECP2 gene, mutations in which cause Rett syndrome, an X-linked, rare, progressive neurodevelopmental disorder.
Following a review of safety data when the adverse event was initially reported, the US Food and Drug Administration allowed the company to proceed with the Phase I/II trial of the gene therapy at a lower dose of 1E15 vector genomes (vg) for both the pediatric cohort as well as the adult and adolescent cohort. Neurogene said it will incorporate this lower dose into its future planning for the design of a registrational clinical trial for NGN-401.
"The entire Neurogene team is sending our deepest condolences to her family and loved ones," a Neurogene spokesperson said in a statement, referencing the patient who died in the clinical trial. "We appreciate the support for our program from the Rett syndrome patient community, the investigators in our trial, and the FDA. Neurogene is motivated by the improvements observed in multiple aspects of Rett syndrome in those who received the 1E15 vg dose, and we look forward to advancing NGN-401."
NGN-401 is under evaluation in the FDA's Support for clinical Trials Advancing Rare disease Therapeutics, or START, pilot program to support gene therapy development for rare diseases. Earlier this month, Neurogene said the first four pediatric patients treated in the trial showed improvement on various functional scales and achieved new developmental milestones.