Second death in gene therapy trial prompts investigation

A second death in a study of Novartis’ spinal muscular atrophy gene therapy Zolgensma (onasemnogene abeparvovec-xioi; AVXS-101) – a potential blockbuster for this rare disease – has prompted an investigation into whether it was related to the treatment.

Last week Novartis announced positive interim results from the study showing that spinal muscular atrophy (SMA) type 1 patients, with a median age of 9.5 months, treated with Zolgensma had prolonged event-free survival, an early and rapid increase in CHOP-INTEND scores and significant milestone achievement compared to untreated natural history.

The Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) scores increased by an average of 7.0 points one month after gene transfer and 11.8 points three months after gene transfer, reflecting improvement in motor function from baseline.

Preliminary assessments showed that three patients could sit without support for at least 30 seconds as of September 27, 2018 (median of 9.4 months), increasing to eight patients who could achieve the same milestone as of December 31, 2018 (median age of 12.5 months).

One of the patients died from respiratory failure, which was deemed by investigators to be unrelated to the treatment – but a second death of a six-month old has promoted another investigation after monitors thought it might be related to Zolgensma.

“Preliminary findings indicate this occurred in the context of a severe respiratory infection followed by neurological complications in a symptomatic SMA Type 1 patient, and was deemed possibly related to treatment by the investigator,” a Novartis spokesman told Reuters.

An FDA decision on the approval of the therapy is expected within weeks. Zolgensma already has high expectations as a potential breakthrough for this rare disease, with many tipping it as a blockbuster that could rake in up to $2.09 billion in sales in 2023.

It will face competition from from Ionis/Biogen’s Spinraza (nusinersen), which has been available in the US since 2016 and the EU since 2017.

Novartis’ treatment could cost as much as $4 million. This would set a record for a pharmaceutical treatment, but the company has said even this price would represent value for money.

Novartis acquired the drug as part of its $8.7 billion acquisition of biotech AveXis last year.