Pfizer: Pfizer to Open First U.S. Sites in Phase 3 Trial of Investigational Gene Therapy for Ambulatory Patients with Duchenne Muscular Dystrophy

Pfizer Inc. (NYSE: PFE) announced plans to open the first U.S. sites in the Phase 3 study evaluating the investigational mini-dystrophin gene therapy, fordadistrogene movaparvovec, in ambulatory patients with Duchenne muscular dystrophy (DMD). This announcement follows a notification from the U.S. Food and Drug Administration (FDA) that the agency has lifted its clinical hold on the Investigational New Drug (IND) application for fordadistrogene movaparvovec and that Pfizer has addressed the agency’s requests related to the potency assay. The global Phase 3 study, CIFFREO, has been ongoing in 11 countries and was paused in December 2021 to implement a protocol amendment following a fatal serious adverse event that occurred in a Phase 1b study in the non-ambulatory cohort. To date, regulatory authorities in the United Kingdom, Canada, Taiwan, Spain and Belgium have approved the re-start of the Phase 3 study and additional global reviews are ongoing. Pending regulatory feedback, Pfizer anticipates that nearly all CIFFREO sites will open by the end of June 2022.

“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,” said Brenda Cooperstone, Chief Development Officer, Rare Disease, Pfizer Global Product Development. “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.”

In December 2021, a fatal serious adverse event occurred in a non-ambulatory participant in the Phase 1b study of fordadistrogene movaparvovec. Like many non-ambulatory DMD patients, the participant had more advanced disease with underlying cardiac dysfunction. Pfizer immediately paused screening, randomization and dosing in all studies of fordadistrogene movaparvovec as the independent external Data Monitoring Committee (eDMC) reviewed the data, and the U.S. FDA subsequently placed the IND on clinical hold.

Regulatory and ethics approvals to resume the CIFFREO Phase 3 ambulatory study, including the FDA’s lift of its clinical hold, follow reviews of data and protocol amendments. The protocol amendments include a seven-day hospitalization period to enable close monitoring and management of patients following administration of gene therapy. In addition, Pfizer has addressed the U.S. FDA’s questions related to the potency assay to enable the trial to proceed in the United States.

Pfizer recognizes the significant unmet needs for new treatment options for non-ambulatory DMD patients. The company is continuing to work with the eDMC and gene therapy experts to assess potential next steps for evaluation of fordadistrogene movaparvovec in this patient population, who are more progressed in their disease.