Despite a new setback for Elevidys in Europe, Roche—which markets Sarepta’s gene therapy outside the U.S.—remains committed to finding a path forward for the one-time Duchenne muscular dystrophy (DMD) treatment in the bloc.
Friday, the European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) recommended against a conditional marketing nod for Roche and Sarepta Therapeutics' Elevidys in DMD patients between the ages of 3 and 7 years who are still ambulatory, meaning they can walk independently.
All patients with DMD, which overwhelmingly affects young boys, eventually lose the ability to walk, Roche noted in a July 25 release on the EMA decision. The average life expectancy for patients with the neuromuscular disease is just 28 years.
"We are disappointed by the CHMP’s negative opinion, given the urgent need for disease-modifying therapies for children in the EU living with Duchenne," Levi Garraway, M.D., Ph.D., Roche’s chief medical officer and head of global product development, said in the company’s announcement.
Citing the need for an effective DMD treatment in the EU, Roche explained it will continue working with the EMA to “explore a potential path forward” for the gene therapy.
“We are confident in the value Elevidys can bring to ambulatory patients,” Garraway added.
The EMA snubbed the drug because data from the main study used to support Roche’s approval bid “failed to show that Elevidys had an effect on movement abilities after 12 months.”
Further, the difference in functional motor improvement scores between Elevidys patients and those on placebo was “not statistically significant,” the EMA explained on its website.
“In addition, although many patients treated with Elevidys were shown to produce a shorter form of the dystrophin protein, the levels of dystrophin could not be linked to an improvement in movement abilities,” the regulator continued.
Roche also presented data for a subgroup of patients that appeared to respond better to Elevidys, though, even in that group, “effectiveness of treatment was not demonstrated,” the EMA concluded.
The decision has no bearing on patients in clinical trials, given Sarepta and Roche paused all Elevidys studies in Europe back in April, the EMA pointed out.
Roche diverged with the EMA’s opinion on its chief Elevidys trial, Embark. While admitting that the study failed to meet its primary endpoint measuring effect on movement ability, Roche stressed in its release that Elevidys demonstrated “clinically meaningful and statistically significant improvements across important secondary endpoints of functional outcome measures” versus placebo.
Longer-term efficacy data from Embark and a three-year pooled efficacy analysis from a trio of separate Elevidys studies also “showed clinically meaningful improvements across key measures of motor function,” the Swiss drugmaker said.
While Roche will continue vouching for Elevidys at the EMA, the treatment is struggling on multiple fronts thanks to mounting safety concerns over Sarepta’s gene therapy platform. Those issues culminated in a temporary shipment pause of Elevidys in the U.S. earlier this week.
Sarepta has reported two Elevidys patient deaths from acute liver failure this year, with the second prompting the company to pause commercial shipments of the gene therapy to non-ambulatory patients in the U.S. in June.
The biopharma subsequently confirmed a third death last week—this time recorded in an older patient with a different form of muscular dystrophy who received an investigational Sarepta gene therapy that uses the same viral vector as Elevidys.
Given the mounting safety concerns, the FDA asked Sarepta to voluntarily pause shipments of Elevidys to all commercial patients last Friday. Though Sarepta initially resisted, the company gave in to the regulator’s request on Monday, with Sarepta’s CEO Doug Ingram citing the need to maintain a “productive and positive working relationship with FDA.”
Roche, for its part, said Wednesday that it would pause Elevidys shipments in ex-U.S. countries where approvals for the gene therapy were based on the FDA’s green lights. The list of affected countries primarily features states in the Gulf Region such as the United Arab Emirates and Qatar.
Despite the pileup of Elevidys struggles over the past week, Roche is sticking by the treatment’s potential and that of the gene therapy field more broadly.
“The reality is that gene therapy will be an important modality in the treatment of human health,” Teresa Graham, CEO of Roche Pharma, told Fierce Biotech during an interview at the company’s headquarters in Basel, Switzerland, this week.
“There is a lot of promise in gene therapy,” she said in response to a question about the Elevidys issues. “I think what the entire industry is learning is that, scientifically, it's just a little harder than we might have thought.”
On Elevidys specifically, Graham said she was “really hopeful that we can find a path forward for this medicine.”
“We clearly need to talk to regulators,” she added. “[W]e clearly need to have some good conversations about the safety—but we do firmly believe in the risk-benefit of this product.”