Phase 3 trial of Pfizer DMD gene therapy fails to meet its goals
Results of CIFFREO study called 'discouraging blow' to DMD community
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The gene therapy developed by Pfizer called fordadistrogene movaparvovec failed to significantly improve motor function in boys with Duchenne muscular dystrophy (DMD) who are able to walk and taking part in a Phase 3 study.
The company says it will evaluate the next steps for the fordadistrogene movaparvovec program and closely monitor all the participants.
“We are extremely disappointed that these results did not demonstrate the relative improvement in motor function that we had hoped,” Dan Levy, MD, PhD, Pfizer’ development head for DMD, said in a company press release.
The CIFFREO trial (NCT04281485) was designed to test the treatment’s safety and effectiveness in boys ages 4-7, against a placebo, for up to a year.
Pfizer plans to share more details at the upcoming Parent Project Muscular Dystrophy (PPMD)’s 30th Annual Conference and other meetings to ensure the information gleaned from the study “can help improve future clinical research and development of treatment options that can improve care for boys living with Duchenne muscular dystrophy,” Levy said.
PPMD called the CIFFREO results a “discouraging blow” to people with DMD and to the study’s participants. “We recognize that every setback is part of the journey toward advancing therapies for Duchenne and Becker [MD], and we draw strength from the resilience and courage of our community,” it stated in a separate press release.
DMD, which affects males more than females, is caused by mutations in the DMD gene that encodes dystrophin, a protein that helps protect muscle cells from damage during movement. The lack of functional dystrophin causes progressive muscle weakness and wasting.
What was fordadistrogene movaparvovec designed to do?
Fordadistrogene movaparvovec was developed to deliver a gene to provide instructions to produce a shortened, but functional dystrophin called “mini-dystrophin” in muscle cells. The gene therapy is delivered using a modified adeno-associated virus by a one-time infusion into the bloodstream. The treatment was expected to slow or stop DMD muscle degeneration.
The CIFFREO study randomly assigned 226 boys who could walk and were on a stable corticoisteroid regimen to the gene therapy, given at 200 trillion vector genomes per kilogram of body weight, or a placebo. Nearly two-thirds of the participants received the gene therapy.
After a year, the boys who received fordadistrogene movaparvovec would get the placebo and boys first given the placebo would receive the gene therapy.
The trial’s primary goal was to assess changes in motor skills at one year using the North Star Ambulatory Assessment total score. The difference between the gene therapy and the placebo wasn’t statistically significant, the results show.
Key secondary measures, such as the time needed to run/walk 10 meters and to rise from the floor, also didn’t support fordadistrogene movaparvovec’s efficacy. Safety data showed mostly mild to moderate side effects, along with treatment-related serious side effects that generally responded to clinical management.
“It has long been our goal to provide much-needed treatment options for boys living with DMD as we’ve worked closely in partnership with the DMD and scientific community for more than 10 years, and we will share additional information on these results as they become available,” Pfizer’s DMD gene therapy team stated in a letter.
Dosing in the second part of CIFFREO is paused following the sudden death of a boy who received the gene therapy in the Phase 2 DAYLIGHT trial (NCT05429372). DAYLIGHT is evaluating the safety and tolerability of fordadistrogene movaparvovec in boys, ages 2 to 3. Pfizer says it’s working to understand what happened.
In a Phase 1b clinical trial (NCT03362502) that enrolled 19 boys with DMD, ages 4-12, the gene therapy helped preserve functions and increase muscle volume up to at least three years, particularly in the youngest patients.
“We want to acknowledge and thank the brave patients and families who participate in clinical trials, despite the absence of guaranteed benefit. Your contributions are invaluable in helping to bring therapies to all in our community,” PPMD said.
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