By Alex Keown


Pfizer terminated two clinical studies evaluating domagrozumab (PF-06252616) for the treatment of Duchenne muscular dystrophy (DMD).

The company announced this morning that it will terminate a Phase II safety and efficacy study and an open-label extension study. Pfizer said the Phase II study did not meet its primary efficacy endpoint, which was to demonstrate a difference in the mean change from baseline in 4 Stair Climb (in seconds) following one year of treatment with domagrozumab, as compared to placebo. Pfizer said that further evaluation of secondary evidence did not support a significant treatment effect. The company said that a decision to terminate the trial was made following a “thorough review of data available at the time of the primary analysis.” The open-label extension study was designed to evaluate the long-term safety and efficacy of domagrozumab. Pfizer also noted that the studies were not terminated due to safety reasons.

“We are disappointed by these results and while we are not progressing with the studies, the data will contribute to a greater understanding of this disease and we will evaluate the total data set to see if there is a place for this medicine in muscular diseases,” Seng Cheng, chief scientific officer of Pfizer’s Rare Disease Research Unit said in a statement. “We are extremely grateful to all those involved with this trial, especially the boys who participated, and their families.”

While Pfizer halted those studies, the company noted that it is continuing its research into developing DMD treatments. Pfizer currently has one ongoing clinical trial in DMD with a gene therapy, PF-06939926, an investigational, recombinant AAV9 capsid carrying a truncated or shortened version of the human dystrophin gene (mini-dystrophin) under the control of a human muscle-specific promoter. The AAV-based gene therapy program came from Pfizer’s acquisition of Chapel Hill, N.C.-based Bamboo Therapeutics. In addition to the DMD therapy, that acquisition provided Pfizer with pre-clinical assets for Friedreich’s Ataxia and Canavan disease, and a Phase I asset for Giant Axonal Neuropathy.

Currently, there is only one approved DMD treatment in the United States, Sarepta Therapeutics’ Exondys 51, which skips the exon 51 mutation in DMD patients.

DMD is associated with specific errors in the gene that codes for dystrophin, a protein that plays a key structural role in muscle fiber function. Progressive muscle weakness in the lower limbs spreads to the arms, neck and other areas. Eventually, increasing difficulty in breathing due to respiratory muscle dysfunction requires ventilation support, and cardiac dysfunction can lead to heart failure. One of the most common fatal genetic disorders, DMD affects approximately one in every 3,500 boys born worldwide. The condition is universally fatal, and death usually occurs before the age of 30.



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