Pfizer's Phase III CIFFREO trial evaluating fordadistrogene movaparvovec, a mini-dystrophin gene therapy for Duchenne muscular dystrophy (DMD), has failed to meet its primary endpoint. The global study, which involved boys aged 4-8, aimed to demonstrate an improvement in motor function as measured by the North Star Ambulatory Assessment (NSAA) scale one year post-treatment compared to placebo.
DMD is a progressive and degenerative disorder characterized by muscle weakness and wasting due to disruptions in dystrophin production. The condition primarily affects boys and is typically diagnosed in early childhood. The CIFFREO trial sought to address this unmet need by delivering a functional dystrophin gene via gene therapy.
Lack of Significant Improvement
The primary endpoint, change in NSAA score at one year, did not show a statistically significant difference between the fordadistrogene movaparvovec and placebo groups. Furthermore, key secondary endpoints, including 10-meter run/walk velocity and time to rise from the floor, also failed to demonstrate a significant benefit with the gene therapy.
Safety Profile and Next Steps
According to Pfizer, the adverse events observed during the trial were mostly mild to moderate in nature, and treatment-related serious adverse events responded to clinical management. The company plans to present more detailed findings from the CIFFREO study at a future medical meeting.
Previous Setbacks and Market Landscape
This is not the first challenge Pfizer has faced with its fordadistrogene movaparvovec program. In 2021, the FDA placed a clinical hold on the investigational new drug application after a participant death in a Phase I study. The hold was lifted in 2022, allowing the study to resume. More recently, in May 2024, Pfizer reported the death of a participant in the DAYLIGHT Phase II study, which evaluated the gene therapy in younger boys aged 2-3. Dosing in the crossover arm of the CIFFREO study was paused following this event.
Currently, Sarepta Therapeutics leads the DMD treatment market with four approved drugs, including Elevidys (SRP-9001), a gene therapy granted accelerated approval by the FDA in June 2023. PTC Therapeutics also markets therapies for DMD, including Translarna (in the EU) and Emflaza (in the US). Other companies like Capricor Therapeutics, Dyne Therapeutics, Solid Biosciences and Wave Life Sciences are also developing therapies for DMD.
