Pfizer's phase 3 gene therapy trial fails for boys with Duchenne muscular dystrophy

Pfizer's phase 3 trial of the investigational gene therapy fordadistrogene movaparvovec has not shown a significant improvement in motor function for boys with Duchenne muscular dystrophy (DMD). This announcement comes shortly after the death of a young participant in a related phase 2 trial named DAYLIGHT, which included boys aged 2 to 3 years. The child, who had received the gene therapy in early 2023, died from cardiac arrest on May 3.

The phase 3 trial, known as CIFFREO, is a double-blind study involving ambulatory boys aged 4 to 7 years. This trial evaluated the use of fordadistrogene movaparvovec, a recombinant adeno-associated virus gene therapy, and utilized a crossover trial design with the DAYLIGHT study. However, after the death of the participant in DAYLIGHT, Pfizer paused dosing associated with the CIFFREO crossover.

CIFFREO's primary goal was to improve motor function compared to a placebo over one year of treatment, assessed by the North Star Ambulatory Assessment. Unfortunately, the trial did not meet this primary endpoint. Additionally, key secondary endpoints, such as the 10-meter run/walk velocity and time to rise, also did not show a significant difference between the gene therapy and placebo.

Despite these setbacks, the overall safety profile of fordadistrogene movaparvovec in the phase 3 trial was described as manageable, with most adverse events being mild to moderate in severity. Pfizer stated that treatment-related serious adverse events could generally be managed clinically.

Pfizer is continuing to monitor all participants in the study and is evaluating the appropriate next steps for the program. "We are extremely disappointed that these results did not demonstrate the relative improvement in motor function that we had hoped," said Dan Levy, M.D., Ph.D., Pfizer’s development head for DMD, in a June 12 release. He added that detailed results from the study would be shared at upcoming medical and patient advocacy meetings. The goal is to use the learnings from this trial to improve future clinical research and development of treatment options for boys with DMD. Levy expressed gratitude to the boys, their families, advocates, and investigators involved in the research.

Previously, Pfizer's Chief Scientific Officer and President of R&D, Mikael Dolsten, M.D., Ph.D., had highlighted the potential of this gene therapy, especially after Sarepta Therapeutics’ confirmatory DMD trial also ended in failure in October 2023. Sarepta had been testing a gene therapy named Elevidys, which was also evaluated using the North Star Ambulatory Assessment. Although Sarepta's trial did not reach statistical significance in the primary endpoint, it achieved significant results on all key prespecified secondary endpoints, including time to rise and the 10-meter walk test. Elevidys currently has accelerated approval for DMD patients aged 4 and 5 years and is awaiting full FDA approval and label expansion, with a decision expected by June 21.

William Blair analysts noted that the recent news from Pfizer’s trial is unlikely to impact the FDA's decision on Elevidys. They believe that Elevidys will gain full approval but are less confident about its label expansion to non-ambulatory patients. William Blair also mentioned that fordadistrogene movaparvovec was not seen as a competitive threat to Elevidys due to safety concerns during its development. The phase 3 failure further diminishes its competitiveness in the market.