Neurogene drops high-dose arm in Rett study after death

The patient affected by a serious adverse event in Neurogene's clinical trial of Rett syndrome gene therapy has now died, but that won't cause the study to be halted.

The FDA has allowed the company to press ahead with the study of NGN-401, although the high-dose (3E15 vg) arm – in which the fatality occurred – has been discontinued.

Neurogene confirmed the death in a filing to the Securities & Exchange Commission (SEC), recording that the subject in the phase 1/2 trial, who was dosed on 5th November and was subsequently reported to be in a critical condition, "has died following complications from a rare and life-threatening hyperinflammatory syndrome associated with systemic exposure to high doses of adeno-associated virus (AAV)."

The company first revealed the serious adverse event with NGN-401 in an update on the trial last week, which showed encouraging signs of efficacy in four patients treated with the lower 1E15 vg dose, including "meaningful gains of skills and developmental milestones."

Shares in the company fell sharply as a result of the side effect with the higher dose, however, as some investors felt it could make NGN-401 less compelling than a rival candidate from Taysha Gene Therapies.

There was another hit on the stock a few days later when Neurogene revealed it had halted enrolment in the high-dose arm after the affected patient took a turn for the worse.

The latest revelation only had a modest impact – with the shares down less than 3% at the time of writing – although, the current price of $15.59 is well below its 52-week high of over $70.

Assuming the safety of the 1E15 vg dose continues to be supported, Neurogene plans to take that forward into a registrational study, and the FDA's decision to allow dosing to continue in the phase 1/2 study is a positive sign.

The company has previously said that it intends to provide an update on the registration trial next year, with additional results from the phase 1/2 study expected in the second half of 2025.

Rett syndrome is a devastating neurological disorder caused mainly by mutations in the MECP2 gene found on the X chromosome.

The disease causes deficits in brain function that lead to behavioural problems, a rapid decline in the ability to speak and carry out manual tasks, as well as seizures, curvature of the spine, and sleep disturbances. It affects about 15,000 girls and women in the US and 350,000 worldwide.

NGN-401 is designed to deliver a working version of MECP2 to Rett patients and is administered as a one-shot intra-cerebroventricular infusion.