Pfizer Discontinues Gene Therapy Program for Duchenne Following Negative Phase 3 Results

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To ensure participant safety, all boys who received the gene therapy in the clinical program will be followed up for long-term safety monitoring.

More than a month after Pfizer announced that its investigational gene therapy fordadistrogene movaparvovec did not meet its primary end point in the phase 3 CIFFREO study (NCT04281485), the company has announced it will discontinue the program altogether. At this time, the company is focused on conducting a more detailed review of the data, which will be shared at future medical and patient advocacy forums.¹

Fordadistrogene movaparvovec, a microdystrophin gene therapy in development for patients with Duchenne muscular dystrophy (DMD), is a recombinant adeno-associated virus serotype 9 (AAV9) capsid carrying a shortened version of human dystrophin gene under the control of a human muscle-specific. The rAAV9 capsid was chosen as the delivery vector because of its potential to target muscle tissue.

CIFFREO, a phase 3 global, multicenter, randomized, double-blind, placebo-controlled study, included ambulatory boys, aged between 4 and 7 years, with a genetic diagnosis of DMD who are on a stable daily regimen of glucocorticoids. After a year’s worth of treatment, the agent failed to meet its primary end point, assessed as change from baseline in the North Star Ambulatory Assessment, relative to placebo. In addition, the gene therapy failed to distinguish itself from placebo on other secondary end points, which included 10-meter run/walk velocity and time-to-rise from floor velocity.

In a letter to the DMD community, the company wrote, "We are greatly saddened by the results, and the CIFFREO outcome is not what any of us hoped for. But we believe there will be much to learn from these findings and hope they can contribute to future research that could lead to future scientific breakthroughs for boys living with DMD."

In addition to thanking those involved with the trial, the company stated that all boys who received the gene therapy in the clinical program will be followed up for long-term safety monitoring. During the initial readout of CIFFREO, the drug showed a manageable safety profile, with mostly reports of mild to moderate adverse events, and treatment-related serious AEs that generally responded to clinical management.

Fordadistrogene movaparvovec was also being assessed in the phase 2 DAYLIGHT study (NCT05429372), a multicenter, single-arm study of 10 boys aged between 2 and 4 years old with DMD. In early May, the company reported a patient death in the study, subsequently pausing dosing associated with the crossover portion of the CIFFREO trial as it gathered more information. Beyond CIFFREO, the dosing pause did not apply to other ongoing triald for the gene therapy as dosing had already been completed for those studies.

In DAYLIGHT, all patients are followed for 5 years after starting treatment, with the primary analysis occurring once all participants have completed 52 years. The study includes those with a confirmed diagnosis of DMD by genetic testing and excludes those with genetic abnormalities in the dystrophin gene. These can be any mutation affecting any exon between exon 9 and exon 13, inclusive; or a deletion that affects both exon 29 and exon 30; or a deletion that affects any exons between 56-71, inclusive.

At the time of the patient death, the company said in a statement that, “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. 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."

REFERENCES
1. Pfizer Duchenne program discontinuation. News release. Cure Duchenne. July 30, 2024. Accessed July 31, 2024. https://cureduchenne.org/research/pfizer-duchenne-program-discontinuation/
2. Pfizer Provides Update on Phase 3 Study of Investigational Gene Therapy for Ambulatory Boys with Duchenne Muscular Dystrophy. News Release. Pfizer. Published June 12, 2024. Accessed July 31, 2024. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-provides-update-phase-3-study-investigational-gene
3. Pfizer. May 7, 2024. Accessed July 31, 2024. https://www.parentprojectmd.org/wp-content/uploads/2024/05/Pfizer-DMD-PAG-Letter_Final.pdf