Pfizer Halts DMD Gene Therapy Trial Following Patient Death to Investigate Cause

Compiled by Fan Dongdong

Pfizer Announces Suspension of Experimental Gene Therapy PF-06939926 for Duchenne Muscular Dystrophy (DMD) in Phase Ib Trial Following Patient Death

This Monday, the pharmaceutical giant announced a patient death in the fixed cohort participating in the company's Phase Ib micro-dystrophin gene therapy trial. Pfizer stated that it was "deeply saddened" to learn about the death of a patient in the PF-06939926 trial. Pfizer is currently collaborating with an independent external data monitoring committee to review the relevant trial data in order to understand the specific cause of the patient’s death following treatment with PF-06939926. The company has also informed the U.S. Food and Drug Administration (FDA) of the related information.

Due to the suspension of the trial by the U.S. FDA, this has also directly slowed down the company’s progress in submitting its investigational new drug application. The suspended trial is evaluating the efficacy of the gene therapy PF-06939926, which is a research-based recombinant adeno-associated virus serotype 9 (rAAV9) capsid that delivers a truncated version of the human dystrophin gene to patients. The company selected the rAAV9 capsid as the delivery vehicle for this therapy because of its potential to target muscle tissue.

Pfizer stated in a press release that the safety and well-being of patients in the clinical trial for gene therapy PF-06939926 remains Pfizer's top priority, and they are committed to sharing more information and updates on the investigation of this death with the medical and patient communities as soon as possible. Previously, data from the Phase Ib study conducted on an outpatient basis in boys showed that, 12 months after infusion, gene therapy PF-06939926 demonstrated lasting and statistically significant improvements across multiple efficacy endpoints, including sustained levels of mini-dystrophin expression and improved scores on the North Star Ambulatory Assessment (NSAA).

It is currently unclear whether the death will impact the ongoing Phase III CIFFREO study in ambulatory boys with DMD, with the first patient starting dosing this past January. CIFFREO is a global, multi-center, randomized, double-blind, placebo-controlled Phase 3 study expected to enroll 99 non-ambulatory male patients aged 4-7 years diagnosed with DMD through genetic testing, on a stable daily regimen of corticosteroids, and negative for AAV9 neutralizing antibodies. The primary endpoint measures the change from baseline at the one-year assessment. Notably, this marks the first Phase 3 DMD gene therapy program to initiate patient enrollment, representing an important milestone.

In October 2020, the gene therapy PF-06939926 received Fast Track designation from the U.S. FDA, as well as Orphan Drug and Rare Pediatric Disease designations from the agency. Muscular dystrophy is an X-linked disease caused by mutations in the gene encoding dystrophin. Dystrophin is a protein required for muscle stability and typically protects normal muscle fibers from degradation. Due to the lack of dystrophin, patients' muscles gradually begin to degenerate, thereby shortening their lifespan. Symptoms of DMD usually appear in early childhood, between the ages of 3 and 5. In the U.S., about 15,000 patients are affected by muscular dystrophy, with a global total of approximately 300,000 patients.

Currently, the United States has approved five therapies for treating DMD, each targeting a subset of the patient population. The four treatments currently on the market are all exon-skipping therapies, with three from Sarepta Therapeutics and one from NS Pharma. The fifth, developed by PTC Therapeutics, is a corticosteroid approved for treating DMD regardless of the specific genetic mutation, providing anti-inflammatory and immunosuppressive effects for patients with DMD.

Reference Source: Pfizer Halts DMD Gene Therapy Trial to Uncover Cause of Patient Death