DMD gene therapy Elevidys linked to new liver failure case

Sarepta Therapeutics and partner Roche have reported a second case of fatal liver failure with their Duchenne muscular dystrophy (DMD) gene therapy Elevidys and stopped using it to treat some patients.

The revelation follows the announcement of another case of liver failure resulting in the death of a 16-year-old boy treated with Elevidys (delandistrogene moxeparvovec) in March, which prompted the two companies to pause several clinical trials of the gene therapy.

Elevidys has been given full approval to treat ambulatory patients with DMD, with an accelerated approval in non-ambulatory patients.

Both fatalities were in non-ambulatory patients, prompting an immediate halt to treatment of the non-ambulatory group in the commercial setting, while enrolment and dosing of non-ambulatory patients "will be immediately paused until additional risk mitigation measures are implemented," according to Sarepta and Roche.

The companies are considering the inclusion of immune-modulating therapies in clinical trial protocols to mitigate the risk of liver damage, and said that treatment of ambulatory DMD patients is not affected.

Liver damage is a well-recognised complication of gene therapies based on adeno-associated virus (AAV) vectors, and other drugs – including Novartis' spinal muscular atrophy (SMA) treatment Zolgensma (onasemnogene abeparvovec) and Astellas' X-linked myotubular myopathy therapy AT132 – have been associated with deaths due to acute liver failure.

One way to reduce the risk is to administer immunosuppressive drugs like corticosteroids to dampen down inflammation of the liver (hepatitis) if biomarkers of liver damage rise after treatment.

"We are deeply saddened by the loss of these two young men and are urgently working to mitigate any risks related to the use of Elevidys," said Roche's chief medical officer Levi Garraway.

"Patient safety is always our highest priority. Therefore, we have recommended halting treatment with Elevidys in non-ambulatory patients with immediate effect."

Elevidys has been on the US market since 2023, with its label expanded last year. It remains under regulatory review in Europe, where it was filed for approval in June of last year by Roche, which licensed ex-US rights to the gene therapy in 2019 for $1.15 billion upfront.

Sarepta's share price has been depressed since the first boy's death and fell further following the latest announcement, down around 37% in pre-market trading this morning to less than $23, a fraction of its 52-week high of more than $173.