A young boy enrolled in a clinical trial testing an experimental Pfizer gene therapy for Duchenne muscular dystrophy has died, the company revealed Tuesday in a letter posted online by a patient advocacy group.

The boy, who received the therapy in early 2023 as part of a Phase 2 study, “passed away suddenly,” the letter said. Pfizer doesn’t yet know the cause or whether the death was associated with its treatment, called fordadistrogene movaparvovec.

“We do not yet have complete information and are actively working with the trial site investigator to understand what happened,” read the letter, which was shared by Parent Project Muscular Dystrophy.

The study is evaluating Pfizer’s therapy in two- to three-year-old boys with Duchenne, a progressive and fatal muscle-wasting condition with few available treatments. It’s one of several currently ongoing, including a Phase 3, placebo-controlled trial in older boys that’s expected to read out results this year. Pfizer has been hoping that data, if positive, could support an approval application.

Development has been slowed by safety concerns before. Another patient died in an earlier study in 2021, leading the Food and Drug Administration to temporarily halt testing. Pfizer subsequently put in place safeguards that allowed its studies to restart. Among the changes was a requirement that patients be closely monitored in a hospital for a week after treatment.

Testing of Duchenne gene therapies has changed more broadly, too, as scientists homed in on a rare, but serious, side effect they judged to be a shared effect of the treatments. Pfizer and Sarepta Therapeutics both modified their late-stage trials to exclude certain patients thought to be at higher risk.

In response to the recent death, Pfizer is pausing treatment in a “crossover” portion of the Phase 3 trial it’s running. This phase involves participants who originally received placebo. Other study activities will continue as planned and, in the meantime, Pfizer is working with regulators and trial monitors to investigate further.

“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,” PPMD said in a statement.

The timing of the boy’s death, if connected to Pfizer’s treatment, would be unusual, according to Brian Abrahams, an analyst at RBC Capital Markets. “Most [serious side effects] associated with [Duchenne] gene therapies have been acute … and we would not expect a delayed toxicity with this mechanism or approach,” Abrahams wrote in a client note.

Pfizer’s therapy works by delivering into the body a shortened version of the gene that’s mutated in people with Duchenne. This gene encodes instructions that enable muscle cells to build a form of a muscle-protecting protein called dystrophin.

If fordadistrogene movaparvovec reaches market, it would become the second gene therapy available for Duchenne. The first, Elevidys from Sarepta Therapeutics, was approved for young children in June 2023. The biotechnology company is working to broaden the approval and, last week, said new labeling could come from the FDA soon.

Editor’s note: This story has been updated with additional detail, including analyst commentary.