Neurogene’s shares fell by 36% as the market opened Monday morning following news that a patient experienced systemic hyperinflammatory syndrome in a Phase I/II clinical trial of Rett syndrome gene therapy NGN-401.
Neurogene has revealed more about the adverse event brought on by a high dose of its Rett syndrome gene therapy. The patient experienced systemic hyperinflammatory syndrome, which is a dangerous but known immune response that can occur with high doses of adeno-associated virus (AAV) gene therapy.
That a patient had suffered a serious adverse event was disclosed last week, when Neurogene reported data from a Phase I/II trial of NGN-401 that showed “consistent, concordant and durable” symptom improvements in patients. Although the company did not reveal the nature of the adverse event at the time, the news sent Neurogene’s shares down 35%.
Now, the company has explained that a female patient remains in critical condition “and the case is continuing to evolve.”
The company’s shares again fell by 36% as the market opened Monday morning to $22.01 apiece. Prior to the disclosure of the adverse event on November 11, Neurogene shares had been trading for about $71 each.
Systemic hyperinflammatory syndrome is a rare and life-threatening immune response that causes aberrant cytokine release and hemophagocytic lymphohistiocytosis (HLH) and multisystem inflammatory syndrome. Essentially, the body’s immune system goes into overdrive in response to a stressor, triggering a massive inflammatory cascade that can lead to irreversible organ dysfunction and even death.
Neurogene reported the event to the FDA after initially being informed of the complication. The agency conducted a review of safety data for NGN-401 and cleared the company to continue testing the gene therapy using the lower dose. The higher dose cohort has been paused and no further patients will be enrolled at that dose.
Enrollment is also paused in the low dose cohort this quarter while Neurogene updates that trial protocol, according to the release.
No other treatment-related serious adverse events have been recorded in the trial, Neurogene said. This includes five patients who received the low dose and the first two participants to receive the high dose.
Stifel analysts said that this complication has occurred in other gene therapy trials before, including with Pfizer’s now discontinued Duchenne muscular dystrophy therapy and Novartis’ approved medicine for spinal muscular atrophy, Zolgensma. The patient in the Pfizer trial died. The firm is hopeful that the FDA cleared Neurogene’s trial to continue.
“We agree initial low-dose efficacy is promising, and we’re encouraged it looks cleaner,” Stifel analysts wrote. “The big caveat is that it’s only a handful of patients and for the stock, safety questions may remain an overhang.”
