RARE Daily

Pfizer Cleared to Restart Phase 3 Study of DMD Gene Therapy

April 28, 2022

Pfizer said it would open the first U.S. sites in its phase 3 study evaluating its experimental mini-dystrophin gene therapy, fordadistrogene movaparvovec, in ambulatory patients with Duchenne muscular dystrophy following the U.S. Food and Drug Administration lifting of a clinical hold on the study.

Photo: Brenda Cooperstone, chief development officer, Rare Disease, Pfizer Global Product Development

In December 2021, a fatal serious adverse event occurred in a non-ambulatory participant in the phase 1b study of fordadistrogene movaparvovec. The participant had more advanced disease with underlying cardiac dysfunction. Pfizer paused screening, randomization, and dosing in all studies of fordadistrogene movaparvovec as the independent external Data Monitoring Committee reviewed the data, and the 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.

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 (DMD) is a serious genetic disease characterized by progressive muscle degeneration and weakness. Symptoms usually manifest in early childhood between the ages of 3 and 5. The disease primarily affects boys. Muscle weakness can begin as early as age 3, first affecting the muscles of the hips, pelvic area, thighs and shoulders, and later the skeletal (voluntary) muscles in the arms, legs and trunk. By their early teens, patients typically lose their ability to walk and the heart and respiratory muscles are also affected, ultimately resulting in premature death. DMD is the most common form of muscular dystrophy worldwide with an incidence of 1 in every 3,500 to 5,000 live male births.

DMD is caused by an absence of dystrophin, a protein that helps keep muscle cells intact. In the absence of dystrophin, muscle cells deteriorate. Fordadistrogene movaparvovec is an investigational recombinant adeno-associated virus serotype 9 (AAV9) capsid carrying a shortened version of the human dystrophin gene (mini-dystrophin) under the control of a human muscle-specific promotor. The AAV9 capsid was chosen as the delivery mechanism because of its potential to target muscle tissue.

“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.”

Author: Rare Daily Staff

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