Pfizer Drops Development of DMD Gene Therapy Fordadistrogene Movaparvovec
The program’s cancellation follows a previous announcement that its phase 3 trial had missed its primary end point.
Pfizer has decided to discontinue development of fordadistrogenemovaparvovec (PF-06939926), an investigational adeno-associated virus (AAV) vector-based gene therapy expressing what Pfizer calls “minidystrophin”, which was being evaluated in the phase 3 CIFFREO study (NCT04281485) for the treatment of Duchenne muscular dystrophy, according to news reported by FirstWord Pharma.1
Notably, the move comes less than 2 months after the company announced that CIFFREO had failed to achieve its primary end point.2 CGTLive® reached out to Pfizer to confirm the news.
“In light of the disappointing results, Pfizer does not have plans to continue development of fordadistrogene movaparvovec,” a Pfizer spokesperson said in a statement issued to CGTLive. “We will continue to closely monitor all participants that have received treatment in the clinical studies, and we are committed to sharing detailed results from the study at medical and patient advocacy forums to ensure that learnings from the trial can help improve future research and development of treatments for boys living with DMD.”
According to FirstWord Pharma, the decision also coincides with Pfizer letting go of approximately 150 employees who were doing work related to fordadistrogene movaparvovec at the company’s facility in Sanford, North Carolina, which had been manufacturing the gene therapy product.1 In June 2024, Pfizer had announced that CIFFREO did not demonstrate improvement in gross motor function on the North Star Ambulatory Assessment for patients treated with the gene therapy in comparison to patients treated with placebo at 1 year posttreatment, the measurement that constituted the trial’s primary end point.2 Pfizer additionally stated that the trial missed the mark on key secondary end points, with patients treated with fordadistrogene movaparvovec showing no significant difference in the change from baseline on 10-meter run/walk test velocity and time to rise from floor velocity compared to patients who received the placebo.
“We are greatly saddened by the results, and the CIFFREO outcome is not what any of us hoped for,” Pfizer’s DMD gene therapy team wrote in a July 30, 2024 letter shared by CureDuchenne.3 “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. 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.”
In terms of safety, fordadistrogene movaparvovec was deemed “manageable” in the context of CIFFREO.2 Most adverse events (AEs) in the study were characterized as mild to moderate in severity. Although some treatment-related AEs occurred, they generally were responsive to clinical management.
Outside of CIFFREO, a patient with DMD treated with fordadistrogenemovaparvovec in the context of the phase 2 DAYLIGHT study (NCT05429372), which includes patients aged 2 to less than 4 years, was reported to have died in May 2024.4 At the time, DAYLIGHT had already completed dosing of patients, but dosing in CIFFREO was paused in response to the event. In a letter to Parent Project Muscular Dystrophy, Pfizer stated that the patient had “passed away suddenly”.3
“We do not yet have complete information and are actively working with the trial site investigator to understand what happened,” the company wrote in the letter.3 “The patient received the investigational gene therapy, fordadistrogene movaparvovec, in early 2023.”
