Third death reported with a Sarepta gene therapy

A third fatality has been recorded among patients receiving treatment with a Sarepta gene therapy, adding to the troubles being faced by the company.

The latest death – in a 51-year-old man in a clinical trial of Sarepta's limb-girdle muscular dystrophy (LGMD) type 2E therapy SRP-9004 (patidistrogene bexoparvovec) – was reported by Bloomberg and follows two recent deaths among teenage boys treated with Roche-partnered Duchenne muscular dystrophy (DMD) gene therapy Elevidys (delandistrogene moxeparvovec).

All three fatalities have been linked to acute liver failure. Damage to the liver is a well-recognised complication of gene therapies based on adeno-associated virus (AAV) vectors, which includes both Elevidys and SRP-9004, and the deaths cast a shadow over all of Sarepta's AAV gene therapy programmes.

It also comes shortly after the beleaguered biotech revealed that it was adding a liver failure warning to Elevidys' label at the request of the US FDA, slashing around a third of its workforce, and restructuring its business to focus on small interfering RNA (siRNA) drug candidates. At the same time, the development of several of its gene therapy candidates, including most of the LGMD candidates, has been paused.

Sarepta said it intended to seek "strategic alternatives," including partnering, for the programmes that it no longer intends to fund directly.

The restructuring measures – which are designed to generate around $120 million in cost savings next year – were welcomed by analysts at Jefferies, who said they would help Sarepta maintain profitability while suggesting that the impact on Elevidys sales, which brought in around $282 million in the second quarter, would be modest given the proven efficacy in DMD patients.

Commenting on the SRP-9004 death, a spokesperson for Sarepta told Bloomberg: "While we do everything possible to ensure patient safety, there is inherent risk in clinical trials, and we are grateful to the courageous patients and families who participate."

Shares in Sarepta have been in the doldrums since the news of the Elevidys deaths and a halt to the use of the gene therapy in non-ambulatory DMD patients was announced, but staged a recovery after the restructuring was announced.

This morning, however, the stock had lost nearly 30% of its value in pre-market trading, falling below $22 after trading at around $150 last year.