RARE Daily

Pfizer Announces Amendment to Ongoing Gene Therapy Phase 3 Trial in DMD

September 28, 2021

Pfizer, in a letter to the nonprofit Parent Project Muscular Dystrophy, said that it had submitted a protocol amendment to its ongoing phase 3 trial of its gene therapy candidate for the treatment of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a rare, fatal neuromuscular genetic disease that occurs in approximately one in every 3,500-5,000 males worldwide. DMD is caused by a change or mutation in the gene that encodes instructions for dystrophin. Symptoms of DMD usually appear in infants and toddlers. Affected children may experience developmental delays such as difficulty in walking, climbing stairs or standing from a sitting position. Disease progression leads to muscle weakness in the lower limbs that spreads to the arms, neck, and other areas. Most patients require full-time use of a wheelchair in their early teens, and then progressively lose the ability to independently perform activities of daily living such as using the restroom, bathing, and feeding. Eventually, increasing difficulty in breathing due to respiratory muscle dysfunction requires ventilation support, and cardiac dysfunction can lead to heart failure. The condition is universally fatal, and patients usually succumb to the disease in their twenties.

Pfizer said three severe adverse events of muscle weakness had occurred, two of which involved myocarditis, all of which were attributed to the gene therapy drug being studies, and which lead to the amended protocol.

Pfizer’s External Data Monitoring Committee reviewed the safety findings and concluded that certain mutations in the dystrophin gene may be associated with a higher risk for these adverse events following treatment with its gene therapy, fordadistrogene movaparvovec. 

The company told PPMD that to ensure the safety of study participants the company has proposed a change to the study protocols that will exclude participation for DMD patients with any mutation (exon deletion, exon duplication, insertion, or point mutation) affecting exons 9 through 13, inclusive, or a deletion that affects both exon 29 and exon 30. These mutations are estimated to represent less than 15 percent of patients with DMD. The proposed changes in the protocol and supportive study documents are currently under review by regulatory authorities and ethics committees. Enrollment at each site must await approval by these governing bodies, which will happen at different times for individual countries and sites. 

PPMD noted that the trial will continue to recruit a total of 99 patients who fit the amended protocol with the clinical sites recruiting for this study outside the United States as Pfizer awaits FDA’s response to their potency assay.

Author: Rare Daily Staff

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