Pfizer's DMD gene therapy fails in Phase III

Pfizer has encountered a significant setback in the development of its gene therapy for Duchenne muscular dystrophy (DMD), a severe muscle-wasting disease. On Wednesday, the pharmaceutical giant announced that its gene therapy, fordadistrogene movaparvovec, failed to meet the primary endpoint in the CIFFREO Phase III trial. This trial was crucial for proving the efficacy of the treatment. Unfortunately, the therapy also did not achieve several key secondary endpoints.

This disappointing outcome follows a series of clinical challenges, including patient fatalities that led to pauses in the program. The first of these safety concerns arose in 2021, halting progress temporarily. More recently, in May, a young boy participating in the Phase II DAYLIGHT trial experienced cardiac arrest, leading to another suspension in patient dosing. The DAYLIGHT trial is focused on enrolling young patients, specifically between the ages of two and three.

The CIFFREO trial involved approximately 99 ambulatory boys aged four to seven who were either given the gene therapy or a placebo. The primary measure of success was the North Star Ambulatory Assessment (NSAA), which evaluates motor function a year after administration. Unfortunately, the results showed no significant benefit in motor function for those receiving the gene therapy compared to those who received the placebo. Additionally, the treatment did not lead to better outcomes in other tests, such as the 10-metre run/walk velocity test and the time-to-rise-from-floor velocity test.

Dan Levy, who leads the development for DMD at Pfizer, expressed profound disappointment over the results. "We are extremely disappointed that these results did not demonstrate the relative improvement in motor function that we had hoped," he said. Levy also mentioned that Pfizer plans to share more detailed results at upcoming medical and patient advocacy meetings. The company aims to use the insights gained from this trial to enhance future clinical research and develop better treatment options for boys suffering from DMD.

Pfizer is now contemplating the next steps for fordadistrogene movaparvovec following this setback. This situation leaves Sarepta's DMD gene therapy, Elevidys (delandistrogene moxeparvovec-rokl), in an advantageous position. Elevidys has already surpassed sales expectations for 2023, and its market status could be further solidified if the FDA agrees to expand its label to include older and non-ambulatory DMD patients. The FDA is expected to make this decision by June 21.

While Pfizer’s trial has not provided the breakthrough that was hoped for, the company’s commitment to sharing its findings aims to contribute to the broader research landscape. This information could prove invaluable for future efforts to develop effective treatments for DMD, a condition that desperately needs new therapeutic options.