DMD gene therapy Elevidys dealt another blow, this time from EU panel

Bad news continues to pile up for the Duchenne muscular dystrophy (DMD) gene therapy Elevidys (delandistrogene moxeparvovec), with a European advisory committee announcing on Friday a decision not to recommend conditional approval. Roche — which has ex-US rights to Elevidys from developer Sarepta Therapeutics — said that it plans to engage with the European Medicines Agency to explore a potential path forward.

"We are disappointed by the…negative opinion," remarked Levi Garraway, Roche's chief medical officer, adding that the company remains "confident in the value Elevidys can bring to ambulatory patients." 

The negative opinion from the Committee for Medicinal Products for Human Use (CHMP) comes on the heels of Roche pausing new Elevidys orders for ambulatory DMD patients in markets that reference the US as the basis for their local approvals. 

Sarepta previously took similar action in the US for non-ambulatory patients in the wake of two deaths from acute liver failure in DMD patients who were administered Elevidys. More recently, it extended that to ambulatory patients as well – in response to some FDA arm-twisting – following the disclosure of a third death involving a patient with limb-girdle muscular dystrophy who had been given one of its experimental gene therapies that uses the same AAVrh74 viral vector as Elevidys.

In explaining its negative decision, CHMP said that the main study submitted by Roche in support of its application in ambulatory individuals aged three to seven years failed to show that Elevidys had an effect on movement abilities after 12 months. Improvements in movement, as measured using the North Star Ambulatory Assessment (NSAA), were seen both in patients on Elevidys and those on placebo, but the 0.65 difference between the two groups on a 34-point scale was not statistically significant.

CHMP added that while many patients treated with Elevidys were shown to produce a shorter form of the dystrophin protein, levels of dystrophin could not be linked to an improvement in movement abilities. Further, in a sub-group of patients who seemed to respond better to Elevidys, the effectiveness of treatment was also not demonstrated.

For related analysis, see Vital Signs: Four key questions for Sarepta, and for a survey of physicians' views of the matter, read Spotlight On: More caution warranted, but gene therapies remain a compelling treatment approach for DMD, neurologist poll reveals.