FDA Clears Pfizer to Resume Phase 3 Gene Therapy Trial for Duchenne Muscular Dystrophy

The FDA has approved the restart of Pfizer’s phase 3 CIFFREO study (NCT04281485) evaluating its experimental mini-dystrophin gene therapy fordadistrogene movaparvovec, formerly known as PF-06939926, for the treatment of Duchenne muscular dystrophy (DMD) in ambulatory patients, according to a statement from the company.¹

“Duchenne muscular dystrophy is a devastating disease with very limited treatment options, and we believe that gene therapy has the potential to significantly impact disease progression,” Brenda Cooperstone, chief development officer of rare disease, Pfizer Global Product Development, said in the statement. “Pfizer is pleased to progress CIFFREO and is working as quickly as possible to activate trial sites as local regulatory and ethics approvals occur. We thank the participants in our clinical trials and their families, as well as the broader Duchenne community, for their ongoing trust and collaboration as we work to advance our investigational gene therapy.”

The CIFFREO trial is underway in 11 countries but was halted in December 2021 amid safety concerns, including the death of a participant in a phase 1b study (NCT03362502) in the non-ambulatory cohort. Now, the FDA has lifted its clinical hold on the investigational new drug (IND) application for fordadistrogene movaparvovec and signed off on the opening of the first US sites, while regulatory agencies in United Kingdom, Canada, Taiwan, Spain, and Belgium have also cleared the trial to resume. Additional reviews are underway and Pfizer expects all CIFFREO sites to reopen by June 2022.

Read More: Unique Challenges With Gene Therapy in Duchenne Muscular Dystrophy

The FDA completed data and protocol amendment reviews, and received more information from Pfizer regarding the potency assay.

“The protocol amendments include a seven-day hospitalization period to enable close monitoring and management of patients following administration of gene therapy,” the company reported.

Fordadistrogene movaparvovec is an investigational adeno-associated virus serotype 9 capsid that delivers a shortened version of the human dystrophin gene (mini-dystrophin). The rAAV9 capsid was chosen as the delivery vector because of its potential to target muscle tissue. It previously received fast track designation from the FDA in October 2020 as well as orphan drug and rare pediatric disease designations in May 2017.

Pfizer dosed the first patient in the CIFFREO trial in January 2021.² The trial’s primary end point is change in North Star Ambulatory Assessment (NSAA) at 1 year from baseline. Participants in the placebo group will be treated with the gene therapy after 1 year and treated participants will switch to placebo after 1 year. Participants will be followed-up for 5 years post-treatment.

Reference:

1. Pfizer to Open First U.S. Sites in Phase 3 Trial of Investigational Gene Therapy for Ambulatory Patients with Duchenne Muscular Dystrophy. Pfizer news release. April 28, 2022. Accessed April 28, 2022. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-open-first-us-sites-phase-3-trial-investigational

2. Pfizer doses first participant in phase 3 study for Duchenne muscular dystrophy investigational gene therapy. News release. Pfizer. January 7, 2021. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-doses-first-participant-phase-3-study-duchenne