Pfizer stops DMD gene therapy development after trial failure
Trial dosing paused in May after patient death
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Pfizer has discontinued development of fordadistrogene movaparvovec, its investigational gene therapy for Duchenne muscular dystrophy (DMD), after recent Phase 3 trial data indicated a failure to improve motor function in boys with the neuromuscular disease.
Patients who have already received the gene therapy in the CIFFREO Phase 3 trial (NCT04281485) or other clinical studies will continue to be monitored for safety reasons.
Pfizer said it will focus on reviewing the data from CIFFREO in more detail, and will share its review with the public in the future.
“We are greatly saddened by the results, and the CIFFREO outcome is not what any of us hoped for,” Pfizer said in a letter sent to patient advocacy groups. “But we believe there will be much to learn from these findings and hope they can contribute to future research that could lead to future scientific breakthroughs for boys living with DMD.”
DMD patients are lacking in dystrophin, a protein that helps protect muscles from damage, due to mutations in the DMD gene.
Trial failed to meet goals
Fordadistrogene movaparvovec was designed to provide patients with a gene encoding production of a shorter-than-normal, but functional, dystrophin protein called mini-dystrophin.
Delivered via one-time infusion into the bloodstream, the gene therapy was expected to slow or stop the muscle degeneration that characterizes DMD. Early clinical trial data supported that, showing that the gene therapy preserved motor function and increased muscle volume in boys with DMD, especially the youngest patients, in a Phase 1b trial (NCT03362502).
In CIFFREO, 226 boys, ages 4-7, who could walk and were on a stable corticosteroid regimen were given the gene therapy or a placebo. After a year, boys given the placebo would receive the gene therapy, and those on the therapy would get a placebo.
The study’s main goal was to assess changes in motor skills after the first year, evaluated using the North Star Ambulatory Assessment. Pfizer announced in June that the study failed to meet this goal, and function was not significantly improved with gene therapy relative to the placebo.
Key secondary efficacy goals related to motor function also were not met, although the treatment was generally well tolerated.
Dosing in the study’s second part was paused in May due to the death of a boy in the Phase 2 DAYLIGHT trial (NCT05429372), which was still being investigated.
“We know how absolutely crucial it is to find transformative treatments for boys that are living with DMD and we want to again thank this incredible community — including but not limited to the participants who have enrolled in trials in the fordadistrogene movaparvovec program, their supportive families, and the trial investigators involved,” Pfizer said.
Pfizer’s decision to pull the therapy means the company is no longer actively developing any new DMD treatments. PPMD, in a press release, called that a “devastating setback” for the DMD community.
PPMD said it will continue to work closely with researchers, industry partners, and the DMD community at large to ensure progress on the DMD treatment. It acknowledged the families who participate in clinical trials “despite the absence of guaranteed benefit,” noting that their efforts are “invaluable in helping to bring therapies to all in our community.”
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