Pfizer revealed that a phase 3 trial for its investigational mini-dystrophin gene therapy, fordadistrogene movaparvovec, in ambulatory patients with Duchenne muscular dystrophy (DMD) did not meet its primary or secondary endpoints.
In the global CIFFREO trial, fordadistrogene movaparvovec failed to demonstrate improvement in motor function among boys 4 to 7 years of age compared to placebo, as assessed by change in the North Star Ambulatory Assessment one year post treatment.
Key secondary endpoints, including 10-meter run/walk velocity and time to rise from floor velocity, also did not show a significant difference between participants treated with fordadistrogene movaparvovec and placebo.
One piece of good news was that, according to Pfizer, the overall safety profile of the therapy in the trial was "manageable," with mostly mild to moderate adverse events, and treatment-related serious adverse events generally responding to clinical management. The study is currently on a dosing pause due to a fatal serious adverse event revealed last month in the phase 2 DAYLIGHT trial, which is evaluating fordadistrogene movaparvovec in younger DMD patients (aged 2-3 years).
In response to the death in the DAYLIGHT trial, Pfizer has paused dosing in the crossover portion of the subsequent phase 3 CIFFREO trial. This was the second pause for the CIFFREO trial, which had been halted back in December 2021, due to the death of a patient in the non-ambulatory cohort of the phase 1b study. After the pause, Pfizer amended the trial protocol to include a seven-day hospital stay for monitoring post-dosing, and resumed the study in March 2022.
Fordadistrogene movaparvovec works by using a modified virus to deliver a functional version of the dystrophin gene directly into muscle cells. This gene encodes a shortened version of the dystrophin protein, called micro-dystrophin, which helps improve muscle function and slow disease progression. The therapy aims to provide a long-term treatment option by compensating for the defective gene responsible for DMD.
Pfizer says it will continue to closely monitor all participants enrolled in the CIFFREO study and is evaluating next steps.
A year ago, Sarepta Therapeutics won approval for its gene therapy, branded Elevidys, a one-time treatment for ambulatory Duchenne patients aged 4 to 5 years.
