NEW YORK – A young boy who had received Pfizer's gene therapy candidate for Duchenne muscular dystrophy (DMD) has died, according to a letter written by the team at Pfizer developing the agent and shared by the patient advocacy group Parent Project Muscular Dystrophy.
The boy, who Pfizer said "passed away suddenly," was participating in the Phase II DAYLIGHT study in which investigators are evaluating the safety and biomarker expression of fordadistrogene movaparvovec in pediatric male patients. The patient had received the gene therapy in early 2023.
Pfizer said it is investigating the death with regulators and an independent data monitoring committee. In the meantime, the company has stopped giving patients fordadistrogene movaparvovec in the crossover portion of another randomized-controlled Phase III trial, called CIFFREO. Dosing has been completed in other ongoing studies of fordadistrogene movaparvovec.
Pfizer did not immediately respond to a request for comment from Precision Medicine Online.
"We do not yet have complete information and are actively working with the trial site investigator to understand what happened," Pfizer said in the letter dated May 7. "The safety and well-being of the patients in our clinical trials remains our top priority, and we are committed to sharing more information with the medical and patient community as soon as we can."
In early results from its first-in-human study of the gene therapy presented last year, Pfizer reported that it had slowed the decline of motor functions in DMD patients.
DMD is a rare, inherited disorder characterized by progressive muscle weakness. The disorder is caused by mutations in the DMD gene, which result in a deficiency of the protein dystrophin. Multiple companies are developing gene therapies that seek to deliver functional DMD transgenes to treat this disease, and in 2023, Sarepta Therapeutics became the first to market with a US Food and Drug Administration-approved product.
This isn't the first potential safety setback seen in studies testing investigational gene therapies for DMD. In fact, in 2021, the FDA instituted a clinical hold on Pfizer's investigational new drug application for fordadistrogene movaparvovec after a patient in a non-ambulatory cohort of a Phase Ib study experienced a fatal serious adverse event. The FDA lifted the hold in April 2022.
Researchers in a preprint paper last year shared results from an investigation into a patient who died after receiving another gene therapy that utilized CRISPR gene-editing and is sponsored by the nonprofit Cure Rare Disease. That investigation found that the patient's death was potentially linked to an immune reaction to the adeno-associated virus vector used to deliver the treatment.
Last year, multiple biopharmaceutical companies developing gene therapies for DMD, including Pfizer and Sarepta, formed a working group to investigate serious adverse reactions seen across clinical trials of their respective candidates, specifically severe muscle weakness and inflammation.
"Our hearts ache for this family, and this loss underscores the critical importance of understanding what transpired to ensure the safety of all individuals participating in clinical trials," Parent Project Muscular Dystrophy said in a statement Tuesday. "As a community, it is imperative that we come together to support each other during this time and work collectively towards making advancements in research while prioritizing safety above all else."