Pfizer Halts Enrollment in DMD Gene Therapy Trial After Patient Death

Pfizer said it halted enrollment in its early-stage trial of its gene therapy for Duchenne muscular dystrophy after the death of a young male patient in the non-ambulatory cohort.

In a community letter to the Parent Project Muscular Dystrophy advocacy group, Pfizer told the advocacy group that they “are actively working with the trial site investigator to understand what happened.”

The company has paused screening and dosing and said it is working with the independent External Data Monitoring Committee to review the data, and has notified the U.S. Food and Drug Administration, which has placed the Investigational New Drug application on clinical hold.

Duchenne muscular dystrophy (DMD) is a rare, fatal neuromuscular genetic disease that occurs in approximately one in every 3,500-5,000 males worldwide. DMD is caused by a change or mutation in the gene that encodes instructions for dystrophin. Symptoms of DMD usually appear in infants and toddlers and include developmental delays such as difficulty in walking, climbing stairs or standing from a sitting position. As the disease progresses, muscle weakness in the lower limbs spreads to the arms, neck and other areas. Most patients progressively lose the ability to independently perform activities of daily living and, eventually, increasing difficulty in breathing due to respiratory muscle dysfunction and cardiac dysfunction. The condition is universally fatal, and patients usually succumb to the disease in their twenties.

The gene therapy in question, PF-06939926, is being tested in a phase 1 study of up to 35 patients who can walk or must use a wheelchair. Pfizer previously reported several serious adverse events in the trial that caused the company to tighten enrollment criteria for the trial, which was to enroll up to 99 patients at first. At the end of September, the company reported three cases of muscle weakness including inflammation of the heart tissue called myocarditis that were seen in patients after treatment a high dose of the gene therapy. The adverse events were attributed to the study therapy, and the external data monitoring committee later concluded that certain mutations were associated with a higher risk for the adverse events.

In November, Pfizer pushed a data readout for the trial, which was expected in 2022, to the first quarter of 2023. PF-06939926, also known as fordadistrogene movaparvovec, has Fast Track designation in the United States and an Orphan Drug status in the United States and the European Union.