Mini-dystrophin Gene Therapy Misses Endpoints in DMD Trial

Results were announced from a phase 3 study evaluating the investigational gene therapy, fordadistrogene movaparvovec, in ambulatory patients with Duchenne muscular dystrophy (DMD).

Fordadistrogene movaparvovec is a recombinant adeno-associated virus, serotype 9 (AAV9) capsid carrying a shortened version of the dystrophin gene. The randomized, double-blind, placebo-controlled CIFFREO study (ClinicalTrials.gov Identifier: NCT04281485) enrolled ambulatory male participants 4 to 7 years of age with a confirmed diagnosis of DMD who were on a stable daily regimen of glucocorticoids. Study participants were randomly assigned to receive a single intravenous infusion of either fordadistrogene movaparvovec or placebo.

The primary endpoint was the change from baseline to week 52 in the North Star Ambulatory Assessment total score, a test that measures gross motor function in children with DMD. Findings showed treatment with fordadistrogene movaparvovec did not lead to statistically significant improvement in motor function compared with placebo. Moreover, the study failed to meet key secondary endpoints; significant differences were not observed in 10-meter run/walk velocity or time to rise from floor velocity.

At this time, the CIFFREO study is on a dosing pause following a fatal serious adverse event in the phase 2 DAYLIGHT trial (ClinicalTrials.gov Identifier: NCT05429372), which is assessing the safety and tolerability of fordadistrogene movaparvovec gene therapy in male participants 2 to 3 years of age with DMD. 

“We are extremely disappointed that these results did not demonstrate the relative improvement in motor function that we had hoped,” said Dan Levy, MD, PhD, Development Head for Duchenne muscular dystrophy, Pfizer. “We plan to share more detailed results from the study at upcoming medical and patient advocacy meetings, with the goal of ensuring that learnings from this trial can help improve future clinical research and development of treatment options that can improve care for boys living with Duchenne muscular dystrophy.”

This article originally appeared on MPR