Neurogene Halts High-Dose Arm of Rett Syndrome Trial After Patient Death
Key Insights
Neurogene's Phase I/II Rett syndrome (search) trial experienced a patient death linked to the higher dose (3E15 vg) of NGN-401 gene therapy, triggering systemic hyperinflammatory syndrome.
The FDA has permitted Neurogene to continue the trial, but only with the lower dose (1E15 vg) of NGN-401, which has shown some clinical benefits in early data.
Neurogene plans to provide further details on registrational trial plans for NGN-401 in the first half of 2025, with more Phase I/II data expected later next year.
Neurogene has discontinued the high-dose arm of its Phase I/II clinical trial for NGN-401, a gene therapy targeting Rett syndrome (search), following the death of a patient. The patient, who received the 3E15 vg dose, developed systemic hyperinflammatory syndrome, a known complication associated with high doses of adeno-associated virus (AAV) gene therapies.
The company disclosed the adverse event in an SEC filing, initially describing it as a treatment-related serious adverse event before revealing the specific diagnosis of systemic hyperinflammatory syndrome. This syndrome is a severe side effect that has been documented in other systemically dosed AAV gene therapies, particularly at doses exceeding 1E14 vg/kg.
The FDA has allowed Neurogene to proceed with the trial using only the lower 1E15 vg dose, which has been cleared for use in pediatric, adolescent, and adult patients. Neurogene intends to advance NGN-401 into registrational studies using this lower dose, contingent on the ongoing trial results.
Clinical Data and Future Plans
Despite the setback, Neurogene reported that the lower 1E15 vg dose of NGN-401 has demonstrated clinically meaningful benefits. In early data, the first four treated patients achieved a "much improved" rating on the Clinical Global Impression Scale of Improvement. Patients also reached key developmental milestones or gained skills in core Rett syndrome (search) domains, including language, communication, hand function, ambulation, and gross and fine motor skills.
Analysts anticipate further details regarding Neurogene's registrational trial plans for NGN-401 in the first half of 2025, with additional data from the Phase I/II study expected later in the year.
Rett Syndrome Context
Rett syndrome (search) is a rare genetic disorder primarily affecting females, occurring in approximately 1 in 10,000 female births. The condition leads to progressive deterioration of motor skills, impaired language and development, breathing problems, scoliosis, and seizures.
Batten Disease Program Suspension
In addition to the challenges in the Rett syndrome (search) program, Neurogene has also suspended its Batten disease (search) program after failing to obtain Regenerative Medicine Advanced Therapy designation from the FDA.