Multiple studies of Sarepta's DMD therapy halted after death

The EMA has called a temporary halt to a phase 2 trial of Sarepta's Roche-partnered Duchenne muscular dystrophy (DMD) gene therapy Elevidys in the wake of the death of a patient who received the treatment.

A notice from the EU regulator notes that Study 302 (ENVOL; NCT06128564) – which started in October 2023 and involved babies and newborns with DMD – has been suspended in five EU member states (Spain, Belgium, France, Germany, and Italy).

Meanwhile, patient advocacy organisation Duchenne UK has published a letter (PDF) from Roche indicating that two more clinical studies of Elevidys (delandistrogene moxeparvovec), namely Study 104 and Study 303, have been halted "until the analysis into the cause of death is complete."

In March, Sarepta revealed that a 16-year-old boy who had been treated with Elevidys died of acute liver failure, which is a known side effect of Elevidys and listed on its labelling and is thought to be linked to the adeno-associated virus (AAV) used to deliver the gene therapy.

The company said at the time that the treatment – which took place in December – may have been complicated by an accompanying infection with cytomegalovirus (CMV), which can infect and damage the liver, causing hepatitis.

Elevidys was approved in the US in 2023 with a label restricted to patients aged four to five who were able to walk (ambulatory) and had its label extended last year to include both ambulatory and non-ambulatory patients aged four and over.

It remains under regulatory review in the EU, where it was filed for approval in June of last year by Roche, which holds marketing rights outside the US.

Study 104 (NCT06241950) is a Sarepta-sponsored phase trial to evaluate the safety, tolerability and expression of Elevidys in association with imlifidase in individuals aged 4 to 9 years with pre-existing antibodies to the AAV vector used in the gene therapy.

Study 303 – also known as ENVISION (NCT05881408) – is a phase 3 trial being run by Sarepta investigating the safety and efficacy of Elevidys in patients aged eight to 17 who are ambulatory as well as a non-ambulatory group with no age limitations.

"We are pausing enrolment and dosing of participants in these studies at EU country study sites, as well as the UK for the Roche-sponsored ENVOL study," Sandra Blum, Roche's global patient partnership leader, who sent the company's letter to Duchenne advocacy groups.

"Patient safety monitoring for already enrolled participants and ongoing collection of data will continue," she added. "Patient safety and well-being are Roche's top priority. We will be collaborating closely with EMA and sharing updates as we have them."

Sarepta's share price – already hammered by news of the boy's death – was down nearly 9% in pre-market trading this morning.