Pfizer’s Phase 3 Trial for DMD Gene Therapy Fordadistrogene Movaparvovec Misses the Mark on Primary End Point

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Pfizer additionally noted that the trial missed the mark on key secondary end points.

Pfizer’s phase 3 CIFFREO study (NCT04281485) evaluating fordadistrogene movaparvovec (PF-06939926), an investigational adeno-associated virus (AAV) vector-based gene therapy expressing what Pfizer calls “minidystrophin”, failed to achieve its primary end point, according to an announcement from the company.1

CIFFREO did not demonstrate improvement in gross motor function on the North Star Ambulatory Assessment for patients treated with the gene therapy in comparison to patients treated with placebo at 1 year posttreatment, the measurement that constituted the trial’s primary end point. Pfizer additionally noted that the trial missed the mark on key secondary end points, with patients treated with fordadistrogene movaparvovec showing no significant difference in the change from baseline on 10-meter run/walk test velocity and time to rise from floor velocity compared to patients who received the placebo.

The company characterized the safety profile of the gene therapy as “manageable” in the phase 3 trial. It noted that adverse events (AEs) were mostly mild to moderate in severity, and treatment-related serious AEs that did occur generally responded to clinical management. Pfizer stated that it is currently assessing its next steps for fordadistrogene movaparvovec, and that it will keep monitoring all of the participants in CIFFREO closely.

“We are extremely disappointed that these results did not demonstrate the relative improvement in motor function that we had hoped,” Dan Levy, MD, PhD, the development head for DMD at Pfizer, said in a statement.1 “We plan to share more detailed results from the study at upcoming medical and patient advocacy meetings, with the goal of ensuring that learnings from this trial can help improve future clinical research and development of treatment options that can improve care for boys living with Duchenne muscular dystrophy. We are grateful for the boys, their families, advocates, and the investigators who have participated in this research and the continuing effort to advance treatment options for this debilitating disease.”

According to its clinicaltrials.gov page, which was most recently updated on April 4, 2024, CIFFREO is active but no longer recruiting new patients. The global, multicenter, randomized, double-blind trial had been enrolling boys aged from 4 to 7 years who have a genetic diagnosis of DMD and are taking prednisone, prednisolone, or deflazacort on a stable daily dosing regimen.

Last month, the company announced that a patient with DMD had died after being treated with fordadistrogene movaparvovec in the separate phase 2 DAYLIGHT study (NCT05429372) evaluating the gene therapy.2 CIFFREO was put on a dosing pause following the fatal AE (DAYLIGHT had already completed dosing prior to the death). Notably, DAYLIGHT’s participants are aged 2 to less than 4 years.

“We do not yet have complete information and are actively working with the trial site investigator to understand what happened,” Pfizer wrote in its letter to Parent Project Muscular Dystrophy.2 “The patient received the investigational gene therapy, fordadistrogene movaparvovec, in early 2023.” The letter noted that the participant had “passed away suddenly”.

Pfizer’s portfolio of gene therapy products also includes fidanacogene elaparvovec-dzkt (Beqvez), an AAV vector-based therapy developed for the treatment of hemophilia B.3 Notably, Beqvez was approved for use by in the United States by the FDA on April 26, 2024. The therapy also received regulatory approval in Canada earlier this year in January.4 The US indication specifically covers the treatment of adults with moderate to severe hemophilia B who currently use factor IX prophylaxis therapy; or who have a history of, or current, life-threatening hemorrhage; or have repeated, serious spontaneous bleeding episodes, and do not have neutralizing antibodies to the AAVRh74var capsid as determined by an FDA-approved test.3

REFERENCES
1. Pfizer provides update on phase 3 study of investigational gene therapy for ambulatory boys with Duchenne muscular dystrophy. News release. June 12, 2024. Accessed June 13, 2024. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-provides-update-phase-3-study-investigational-gene
2. Letter. Pfizer. https://www.parentprojectmd.org/wp-content/uploads/2024/05/Pfizer-DMD-PAG-Letter_Final.pdf
3. U.S. FDA Approves Pfizer’s BEQVEZ™ (fidanacogene elaparvovec-dzkt), a One-Time Gene Therapy for Adults with Hemophilia B. News release. Pfizer. April 26, 2024. Accessed June 13, 2024. https://www.businesswire.com/news/home/20240425269649/en/U.S.-FDA-Approves-Pfizer%E2%80%99s-BEQVEZ%E2%84%A2-fidanacogene-elaparvovec-dzkt-a-One-Time-Gene-Therapy-for-Adults-with-Hemophilia-B
4. Health Canada approves Pfizer Canada's gene therapy in hemophilia B. News release. Pfizer Canada. January 3, 2024. Accessed June 13, 2024. https://www.newswire.ca/news-releases/health-canada-approves-pfizer-canada-s-gene-therapy-in-hemophilia-b-841249479.html
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