UPDATE: Young boy's fatal cardiac arrest prompts dosing pause in Pfizer's phase 3 gene therapy trial

A young boy with Duchenne muscular dystrophy (DMD) participating in Pfizer’s phase 2 gene therapy trial has died, the pharma shared in a May 7 letter (PDF) cited by nonprofit Parent Project Muscular Dystrophy.

"On May 3, a fatal serious adverse event was reported as cardiac arrest for a participant in the phase 2 DAYLIGHT study," a Pfizer spokesperson told Fierce Biotech via email May 8. "We are working with the investigator to gather information. Pfizer, together with the independent external data monitoring committee, is in the process of reviewing the data to understand the potential cause."

The boy had received Pfizer’s fordadistrogene movaparvovec, an investigational recombinant adeno-associated virus gene therapy, in early 2023, according to Pfizer's letter. He was part of a trial called DAYLIGHT that included boys aged 2 to 3 years old.

Initial dosing for Pfizer’s phase 3 CIFFREO trial, which uses a crossover trial design and is investigating fordadistrogene movaparvovec in boys with DMD ranging from 4 to less than 8 years old, was also completed in 2023.

In light of the patient death, Pfizer has paused dosing associated with the crossover portion of CIFFREO. The pharma is also working with regulators as more information becomes available.

Besides the halt to CIFFREO dosing, trials will continue as scheduled. Other ongoing trials evaluating the gene therapy have already finished the dosing phase. 

“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,” Pfizer wrote in the letter. “We are also aware that many in the patient community are hopeful about the potential benefit of fordadistrogene movaparvovec for the treatment of DMD, and we will continue to collect data from our trials to evaluate its ability to address this disease.”

The DAYLIGHT study is assessing the safety and dystrophin expression of fordadistrogene movaparvovec and has a primary completion date set for the end of this year, according to ClinicalTrials.gov.

Back in October 2023, Pfizer Chief Scientific Officer and President of R&D Mikael Dolsten, M.D., Ph.D., called the investigational gene therapy “the main game in town” on a quarterly earnings call. The commentary came directly after a confirmatory trial for Sarepta Therapeutics’ DMD candidate Elevidys failed to hit the primary goal of a pivotal study.

At the time, Dolsten said Pfizer’s candidate, also known as PF-06939926, has “shown a very consistent effect across biomarkers and functional endpoints.”

This isn't the first death to occur among a patient who has received PF-06939926. Back in December 2021, Pfizer reported the death of a young male patient in a phase 1 DMD trial. The company paused screening and dosing in the study, and the FDA also placed a clinical hold on the study.

Even before that, the pharma had previously recorded safety concerns tied to the therapy when it was in a phase 3 trial testing ambulatory function. After three adverse events were reported, Pfizer trimmed the study protocol to exclude patients with certain gene mutations. 

DMD is a rare genetic disease that leads to progressive muscle degeneration. The condition affects about one in every 5,000 live births and primarily affects boys.

Editor's note: This article was updated at 10:50 a.m. ET on May 8 to include a statement from Pfizer.