Neurogene has introduced a new monitoring and treatment system for its adeno-associated virus (AAV) gene therapy after a Rett syndrome patient died during a clinical trial.
Announced during the American Society of Gene and Cell Therapy (ASGCT) Annual Meeting, Neurogene said the algorithm is intended to reverse the rare, severe hyperinflammatory syndrome haemophagocytic lymphohistiocytosis (HLH), which has been associated with systemic exposure to high doses of AAV gene therapy.
Go deeper with GlobalData
The protocol includes daily monitoring for elevated ferritin levels, fever, and falling blood counts (cytopenia), called the three Fs, during the first week after dosing. These initial signs are present in more than 90% of patients with HLH, according to the HLH-2004 study on which HLH treatment guidelines are based. Treatment includes high-dose corticosteroids as first-line treatment, and Amgen’s Kineret (anakinra), an IL-1 receptor agonist, as second-line treatment.
The company initially announced the adverse event (AE) on 11 November, with their condition deteriorating before the patient’s death was announced on 20 November. The Rett patient was the third person to receive the high dose of NGN-401.
The company’s stock, listed on the NASDAQ exchange, is expected to drop by 7.12% at market open today (19 May). Between the initial AE announcement and today’s news, the company’s stock has dropped by 74.84%.
Phase I/II trial continuing
Neurogene is advancing its Phase I/II trial (NCT05898620) of NGN-401 gene therapy for Rett syndrome with a lower dose level of 1E15 vg. The company said it is not aware of any case of HLH reported at this dose level in AAV gene therapy.
US Tariffs are shifting - will you react or anticipate?
Don’t let policy changes catch you off guard. Stay proactive with real-time data and expert analysis.
By GlobalDataNeurogene CEO and founder Dr Rachel McMinn said: “We appreciate the opportunity that ASGCT is providing for us to share findings related to HLH and the evidence-based recommendations for how to monitor, detect and treat this rare, hyperinflammatory syndrome in the context of AAV gene therapy.
“As we connect with the gene therapy community to provide this information, our hope is that it spurs adoption of the early monitoring and treatment algorithm and increases propensity for sharing trial findings from which others can learn.”
Neurogene has incorporated monitoring and treatment protocol into its Phase I/II clinical trial of NGN-401 for Rett syndrome despite the use of a lower dose in the E13 vg/kg range.
Not first fatal AE from gene therapy
Other companies have also seen fatal AEs associated with their gene therapies. In March 2025, Sarepta and Roche announced that a Duchenne muscular dystrophy (DMD) patient dosed with its gene therapy Elevidys (delandistrogene moxeparvovec-rokl), a single-dose AAV-based gene therapy, had died. This led to a pause in the clinical development of Elevidys, however, this pause has since been lifted.
Last year, Pfizer terminated the development of its gene therapy for DMD after a patient from the Phase II DAYLIGHT trial (NCT05429372) died following a cardiac arrest.
Editorial content is independently produced and follows the highest standards of journalistic integrity. Topic sponsors are not involved in the creation of editorial content.
