Neurogene has dropped plans to keep studying the high dose of its Rett syndrome gene therapy because of an adverse event that has left a patient in critical condition. The discontinuation has pushed back the anticipated completion of enrollment in the low-dose cohort.
New York-based Neurogene reported a treatment-related serious adverse event (SAE) in a phase 1/2 trial of its Rett candidate NGN-401 one week ago. The biotech said it learnt of the adverse event on the day of the statement and only revealed the SAE happened in the third patient in the high-dose arm and was consistent with the known risks of adeno-associated virus (AAV) gene therapy.
Neurogene shared more information about the SAE and its implications for the development of NGN-401 on Monday. The patient received the gene therapy on Nov. 5 and subsequently showed signs of systemic hyperinflammatory syndrome, a condition seen in some people who receive high, systemic doses of AAV.
The life-threatening condition is associated with aberrant cytokine release. Neurogene said the patient is in critical condition and the case is continuing to evolve. The case is the only treatment-related SAE seen to date in the study, which has given the low dose to five people and the high dose to three patients.
The FDA has reviewed the safety data and allowed Neurogene to keep studying the low dose, according to the company. Neurogene paused the high-dose cohort when it told the FDA about the adverse event. The biotech doesn’t plan to enroll further patients in the high-dose arm. Neurogene’s share price fell 20% to below $28 in premarket trading on Monday.
Christine Mikail, chief financial officer at Neurogene, commented on the adverse event on a conference call last week. Speaking hours after learning of the adverse event, Mikail said the adverse event was “not somewhat surprising as a result of the 3x difference in the dose.”
The biotech wasn’t waiting on high-dose data “as it relates to the efficacy picture,” Mikail said. Rather, the cohort was “really dose exploration to see if we could, based on the biodistribution data that we saw non-clinically, be able to push the efficacy.” The attempt to push the efficacy has left a patient in critical condition.
Neurogene no longer expects to finish enrollment in the low-dose cohort in the fourth quarter because of the need to update the protocol to reflect its discontinuation of the high dose. The biotech is targeting the same market as Taysha Gene Therapies. Both companies have MECP2 gene therapies in the clinic.