Pfizer's gene therapy flunks phase 3 Duchenne trial

Pfizer recently announced that its phase 3 trial for the investigational mini-dystrophin gene therapy, fordadistrogene movaparvovec, did not achieve the primary or secondary endpoints in treating ambulatory patients with Duchenne muscular dystrophy (DMD). The global CIFFREO trial tested the therapy on boys aged 4 to 7 and found no significant improvement in motor function compared to a placebo, as evaluated by the North Star Ambulatory Assessment one year after treatment.

Additionally, key secondary endpoints, such as 10-meter run/walk velocity and time to rise from floor velocity, also showed no meaningful differences between the treated group and the placebo group. Despite the disappointing efficacy results, Pfizer reported that the overall safety profile for the therapy was "manageable." Most adverse events were mild to moderate, and serious adverse events related to the treatment generally responded well to clinical interventions.

The trial, however, is currently on a dosing pause following a fatal serious adverse event reported last month in the phase 2 DAYLIGHT trial, which assesses fordadistrogene movaparvovec in younger DMD patients aged 2-3 years. Following this incident, Pfizer paused dosing in the crossover phase of the CIFFREO trial. This marks the second pause for the CIFFREO trial; the first pause occurred in December 2021 after a patient in the non-ambulatory cohort of a phase 1b study died. Pfizer then amended the trial protocol to include a seven-day hospital stay for post-dosing monitoring and resumed the study in March 2022.

Fordadistrogene movaparvovec operates by employing a modified virus to deliver a functional dystrophin gene directly into muscle cells. This gene encodes micro-dystrophin, a shortened version of the dystrophin protein, which is intended to improve muscle function and slow the progression of the disease. The therapy aims to offer a long-term treatment solution by compensating for the defective gene responsible for DMD.

Pfizer has committed to closely monitoring all participants enrolled in the CIFFREO study and is currently evaluating the next steps. This development comes on the heels of Sarepta Therapeutics receiving approval for its gene therapy, Elevidys, a one-time treatment for ambulatory Duchenne patients aged 4 to 5 years, about a year ago.