NEW YORK – Neurogene is no longer enrolling patients in the high-dose cohort of its ongoing Phase I/II clinical trial of its Rett Syndrome gene therapy, NGN-401, after a patient from that cohort developed a treatment-related serious adverse event. The patient is in critical condition, according to the company.
Neurogene last week reported that three patients had received NGN-401 in the high-dose cohort of the trial. The open-label, single-arm Phase I/II clinical trial launched last year and is investigating the safety, tolerability, and preliminary efficacy of NGN-401 in high- and low-dose cohorts of female pediatric patients with Rett syndrome. NGN-401 uses an adeno-associated virus (AAV) serotype 9 vector to deliver a full-length copy of the MECP2 gene, mutations in which lead to the X-linked, rare, and progressive neurodevelopmental disorder.
Two of the patients in the high-dose cohort had a favorable safety profile, the company said, but the third patient, who was dosed on Nov. 5, developed systemic hyperinflammatory syndrome, a rare and life-threatening immune response. The condition is a known complication that may arise following systemic exposure to high doses of AAV-based gene therapies. The adverse event is linked to aberrant cytokine release, and may include hemophagocytic lymphohistiocytosis and multisystem inflammatory syndrome.
The company paused use of the high-dose therapy after learning of the adverse event and no longer plans to enroll any participants in that cohort. However, after reviewing NGN-401's safety data, the US Food and Drug Administration is allowing Neurogene to continue testing the gene therapy at the lower dose. Now, the company will have to update the trial protocol, and as a result, Neurogene said it no longer expects to complete enrollment in the low-dose cohort this year.
There have been no other treatment-related serious adverse events in the trial, including among the five patient treated in the low-dose cohort and the other two patients from the high-dose cohort. All treatment-related adverse events in the low-dose cohort have been mild and most treatment-related adverse events associated with AAV gene therapy have been treatable with steroids and have resolved or are resolving, Neurogene said.
At market close Friday, Neurogene's stock price was $34.51 per share, but when the Nasdaq opened Monday morning, its stock price had dropped 31 percent to $23.79.
Neurogene also said last week that it would no longer be advancing its gene therapy for CLN5 Batten disease, NGN-101, after the FDA declined to grant it a regenerative medicine advanced therapy designation. Earlier this month, it entered into a securities purchase agreement for a $200 million private investment in public equity financing to partly fund enrollment in the Phase I/II NGN-401 clinical trial.