The latest trial data failed to demonstrate domagrozumab’s potential to prevent disease progression or improve patient’s physical capacity, as assessed by mean changes (in seconds) from baseline in the 4 Stair Climb test compared to placebo.
Also, data collected with other secondary measures of effectiveness did not show signs of significant therapeutic effect in the domagrozumab-treated groups.
After a comprehensive review of the available data comprising at least one year of follow-up of all 121 DMD patients enrolled in the Phase 2 trial (NCT02310763), Pfizer decided to stop this study and an open-label extension study (NCT02907619). The company emphasized that the studies are not being halted 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, PhD, said in a press release. Cheng is senior vice president and chief scientific officer of Pfizer’s Rare Disease Research Unit.
The Phase 2 trial involved more than 60 clinical centers in the United States, Canada, Europe, and Japan. It enrolled boys aged 6 to 15 who had been diagnosed with DMD regardless of the underlying genetic mutation.
The study was planned to evaluate the safety and effectiveness of monthly administration of increasing dosage of domagrozumab in comparison with a placebo after one and two years of treatment.
The Phase 2 open-label extension study was designed to further explore the long-term safety and effectiveness of domagrozumab, following the patients for up to four years of treatment with the therapy.
“We are extremely grateful to all those involved with this trial, especially the boys who participated, and their families,” Cheng said.
The company will continue to review the Phase 2 trial data to have a better understanding of the disease and the treatment features that could be of relevance. Pfizer said it will share the trial results with the scientific and patient community.
Despite the domagrozumab setback, Pfizer announced it will continue to develop new therapies for patients with DMD and other rare neuromuscular diseases. The company is currently exploring the potential of an investigational dystrophin gene therapy product, PF-06939926.
PF-06939926 is an investigational therapy that takes advantage of a widely used and safe carrier, the adeno-associated virus serotype 9 (AAV9) capsid, to transport a mini-version of functional dystrophin gene specifically to the muscles.
The investigational gene therapy was granted orphan drug and pediatric rare disease designations by the U.S. Food and Drug Administration, and Orphan Medical Product Designation by the European Medicines Agency in May 2017.
Its safety and early efficacy is currently being evaluated in Phase 1b clinical trial (NCT03362502) in DMD boys age 5 to 12. The trial is currently recruiting participants in several clinical sites in the United States.