Novartis says patient death not caused by gene therapy Zolgensma

Novartis' AveXis unit announced Thursday that the death of a patient who received the gene therapy Zolgensma (onasemnogene abeparvovec-xioi) for the treatment of spinal muscular atrophy (SMA) Type 1 was deemed not to have been caused by brain inflammation. Investigators determined that the patient in the Phase III STR1VE-EU trial died from hypoxic-ischaemic brain damage with respiratory tract infection as the underlying cause, while there was no evidence of an inflammatory central nervous system process or toxic or treatment-related brain damage.

Dave Lennon, chief executive of AveXis, said "we had been concerned about the potential...that Zolgensma might have been causing brain inflammation. In this case, the original diagnosis, and that association, hasn't held true." The autopsy report indicated that Zolgensma could have potentially contributed to the concurrent events of abnormal liver function tests, abnormal blood tests and low blood pressure that led to hospitalisation of the patient, although AveXis noted that these are known side effects of the gene therapy.

Zolgensma was approved by the FDA in May based on results of the late-stage STR1VE-US study. In that trial, one patient died from respiratory failure, which AveXis noted was deemed to be unrelated to treatment. The gene therapy is also under regulatory review in the EU and Japan, with decisions expected later this year.

Alongside the update on the patient death, AveXis detailed new data on Zolgensma at the European Paediatric Neurology Society (EPNS) congress, including results from an ongoing long-term follow-up of the Phase I START study. The trial is evaluating a one-time intravenous infusion of Zolgensma in SMA Type 1 patients experiencing onset of clinical symptoms before six months of age. The company noted that as of May 31, all 10 patients enrolled in the follow-up, who have an average age of 4.2 years, are alive and continue to maintain developmental milestones.

Meanwhile, Novartis has been facing criticism over how it dealt with a recent data manipulation controversy involving Zolgensma, including delays in informing the FDA about the problem. Earlier this month, CEO Vas Narasimhan pledged that the drugmaker would notify the agency within five business days of any "credible allegation" impacting data integrity that could affect its pending marketing applications in the US. 

For related analysis, see ViewPoints: Novartis scrambles to cover its bases in data manipulation fallout, and ViewPoints: Data manipulation an optical nightmare for Novartis.

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