Pfizer’s Duchenne Gene Therapy Fails to Meet Primary End Point in Phase 3 CIFFREO Trial

According to a new announcement, fordadistrogene movaparvovec (previously known as PF-06939926), Pfizer’s investigational mini-dystrophin gene therapy, did not meet its primary end point of improvement in motor function among ambulatory patients with Duchenne muscular dystrophy (DMD) in the phase 3 CIFFREO study (NCT04281485).¹ The company noted that it will continue to closely monitor all participants enrolled in CIFFREO, and will evaluate appropriate next steps for this program.

In the trial, the gene therapy failed to achieve the primary end point, which investigators assessed by the change from baseline in the North Star Ambulatory Assessment at 1 year following treatment. The findings also did not show a significant difference between patients treated with the therapy and placebo in the secondary end points, which included 10-meter run/walk velocity and time-to-rise from floor velocity. The company noted that the overall safety profile of the treatment was manageable, with mostly reports of mild to moderate adverse events (AEs), and that treatment-related serious AEs generally responded to clinical management.

“We are extremely disappointed that these results did not demonstrate the relative improvement in motor function that we had hoped. We plan to share more detailed results from the study at upcoming medical and patient advocacy meetings, with the goal of ensuring that learnings from this trial can help improve future clinical research and development of treatment options that can improve care for boys living with Duchenne muscular dystrophy,” Dan Levy, MD, PhD, development head for DMD at Pfizer, said in a statement.¹ “We are grateful for the boys, their families, advocates, and the investigators who have participated in this research and the continuing effort to advance treatment options for this debilitating disease.”

Top Clinical Takeaways

Fordadistrogene movaparvovec did not show significant improvement in motor function for patients with Duchenne muscular dystrophy (DMD) in the phase 3 CIFFREO study.
The gene therapy also failed to demonstrate significant differences in secondary end points such as 10-meter run/walk velocity and time to rise from floor velocity.
Despite the disappointing results, Pfizer remains committed to advancing treatment options for DMD, with plans to share detailed findings from the trial in future meetings.

CIFFREO is a phase 3 global, multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of fordadistrogene movaparvovec investigational gene therapy among ambulatory boys, aged between 4 and 7 years, with a genetic diagnosis of DMD who are on a stable daily regimen of glucocorticoids. Currently, dosing is paused for the CIFFREO trial because of a fatal serious adverse event reported in a patient in May 2024 from the phase 2 DAYLIGHT trial (NCT05429372).² The company noted that it is still actively working to gather additional information on the event to understand the potential cause.

DAYLIGHT is a multicenter, single-arm study assessing the safety and tolerability of the gene therapy in a small cohort of 10 boys aged between 2 and 4 years old with DMD. In the trial, all patients are followed for 5 years after starting treatment, with the primary analysis occurring once all participants have completed 52 weeks. The study includes those with a confirmed diagnosis of DMD by genetic testing and excludes those with genetic abnormalities in the dystrophin gene. These can be any mutation affecting any exon between exon 9 and exon 13, inclusive; or a deletion that affects both exon 29 and exon 30; or a deletion that affects any exons between 56-71, inclusive.

"The safety and well-being of the patients in our clinical trials remains our top priority, and we are committed to sharing more information with the medical and patient community as soon as we can. We are also aware that many in the patient community are hopeful about the potential benefit of fordadistrogene movaparvovec for the treatment of DMD, and we will continue to collect data from our trials to evaluate its ability to address this disease," the Pfizer DMD gene therapy team wrote.²