Patient Death Reported in Phase 1b Mini-Dystrophin Gene Therapy Trial in DMD


The FDA has placed the investigational new drug application for the treatment on clinical hold.

Seng Cheng, PhD, senior vice president and chief scientific officer, rare disease research unit, Pfizer

Seng Cheng, PhD

A patient with Duchenne muscular dystrophy (DMD) participating in Pfizer’s phase 1b mini-dystrophin gene therapy trial (NCT03362502) has died, the company announced on December 20th. The open-label study is evaluating fordadistrogene movaparvovec, formerly known as PF-06939926, an investigational AAV9 gene therapy designed to treat DMD.1

According to a letter from the gene therapy team at Pfizer sent to advocacy organization Parent Project Muscular Dystrophy, the patient was part of the non-ambulatory cohort and screening and dosing in the trial have been paused while experts review data alongside the independent External Data Monitoring Committee. In addition, the FDA has placed the investigational new drug application on clinical hold.

“On behalf of everyone at Pfizer, we extend our sympathies to his family, friends, and those closest to his care,” the Pfizer DMD gene therapy team said in the letter.1 “At this time, we do not have complete information and are actively working with the trial site investigator to understand what happened.”

“The safety and well-being of the patients in our clinical trial remains our top priority, and we are committed to sharing more information with the medical and patient community as soon as we can,” the team added.1

In 2019, preliminary data from the phase 1b trial that were presented at the 25th Annual Parent Project Muscular Dystrophy (PPMD) Connect Conference in Orlando, Florida showed that at 2 months post-dosing, there was detectable mini-dystrophin immunofluorescence signals with the therapy. An average of 38% positive fibers were collected from those who were administered PF-06939926 at 1E14 vg/kg and a mean of 69% positive fibers were taken from participants who received PF-06939926 at 3E14 vg/kg.2

The separate, ongoing phase 3 CIFFREO trial (NCT04281485) of the treatment in DMD underwent a protocol modification in September 2021 following 3 serious adverse events (SAEs) involving muscle weakness. Two SAEs involved myocarditis, with all SAEs found to be associated with treatment.3

The amendment excluded patients with DMD who had any mutation affecting exons 9 through 13, inclusive, or a deletion affecting both exon 29 and 30, which are estimated to affect less than 15% of patients with DMD. The decision followed a report by Pfizer’s External Data Monitoring Committee, which found that these mutations in the dystrophin gene may be associated with adverse event risk after treatment with fordadistrogene movaparvovec. The trial was anticipated to enroll 99 patients who fit the amended protocol, recruiting for sites outside of the US while waiting on the FDA’s response to Pfizer’s potency assay.

1. Pfizer announces patient died in the non-ambulatory cohort of its phase 1b mini-dystrophin gene therapy trial for Duchenne muscular dystrophy. December 20, 2021.
2. Pfizer presents initial clinical data on phase 1b gene therapy study for Duchenne muscular dystrophy. News release. Pfizer. June 28, 2019.
3. Pfizer announces protocol amendment for gene therapy clinical program for DMD. September 28, 2021.
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