Alder Hey Children's NHS Foundation Trust

Pictured: Sign at Pfizer’s world headquarters in New York iStock , JHVEPhoto Pfizer’s investigational Duchenne muscular dystrophy gene therapy, fordadistrogene movaparvovec, failed in a late-stage study to significantly improve motor function in patients versus placebo. Pfizer on Wednesday announced that its investigational Duchenne muscular dystrophy gene therapy, fordadistrogene movaparvovec, fell short of its primary efficacy endpoint in the Phase III CIFFREO study. The company did not provide specific data in its announcement, only revealing that the gene therapy candidate was unable to significantly improve motor function in boys aged four to seven years, compared to placebo. Fordadistrogene movaparvovec also failed key secondary endpoints, including 10-meter run/walk velocity and time to rise from floor velocity. Despite showing no significant signals of efficacy, fordadistrogene movaparvovec had a manageable safety profile, with most adverse events being mild to moderate in severity. Treatment-related serious toxicities generally responded to management. Dan Levy, development head for Duchenne muscular dystrophy (DMD) at Pfizer, said in a statement that the company is “extremely disappointed” by the results. “We plan to share more detailed results from the study at upcoming medical and patient advocacy meetings” to help improve future research on DMD and develop effective treatment options for the disease, Levy said. Pfizer will continue to monitor study participants while it evaluates the next best steps for fordadistrogene movaparvovec, according to the announcement. Mainly afflicting young boys between two and three years of age, DMD is a severe genetic disorder that involves progressive muscular degeneration. The disease typically manifests initially as weakness and difficulties moving, before eventually affecting vital organs and leading to various complications, such as respiratory failure. DMD is caused by mutations to the gene encoding for the dystrophin protein, which is important for the stability and function of muscles. Fordadistrogene movaparvovec addresses the underlying cause of DMD by delivering a shortened but functional copy of the dystrophin gene. The candidate uses an AAV9 capsid delivery mechanism to specifically target muscle tissue. In addition to CIFFREO, Pfizer is assessing fordadistrogene movaparvovec in a Phase II DMD study. In May 2024, the pharma announced that a patient in the study “passed away suddenly” but did not provide the cause of death. In December 2021, Pfizer reported another patient death associated with fordadistrogene movaparvovec, which led the pharma to pause screening and dosing in its Phase Ib study. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com .