Pfizer said it will halt two clinical studies of its mid-stage Duchenne muscular dystrophy (DMD) candidate domagrozumab (PF-06252616) following its failure in a Phase II trial, while insisting that it will continue research in DMD and rare neuromuscular diseases.
The pharma giant acknowledged that domagrozumab did not meet its primary efficacy endpoint in the Phase II B5161002 trial (NCT02310763), namely demonstrating a difference in the mean change from baseline in 4 Stair Climb (in seconds) following one year of treatment with versus placebo in DMD patients.
That assessment, Pfizer said, followed a primary analysis in which all study participants—121 boys aged 6 to 15 with DMD, regardless of underlying mutation—were evaluated after one year of treatment, including participants who were in the trial beyond one year.
In addition, no significant treatment effect was seen following an assessment of domagrozumab’s ability to meet the study’s 25 secondary endpoints.
Domagrozumab is the second DMD candidate to suffer clinical setbacks in the past two months. In June, Summit Therapeutics said it would halt development of its DMD candidate ezutromid after it failed a Phase II trial, and take unspecified cost-cutting measures.
Pfizer furnished no detailed data about domagrozumab’s failure in its announcement today, only saying it would continue to review data and will share results with researchers and the community of DMD patients.
Also being halted is an open-label extension study (NCT02907619) designed to assess the safety, efficacy, pharmacodynamics, and pharmacokinetics of intravenous dosing of PF 06252616 in boys with DMD from baseline up to four years.
‘Disappointed by These Results’
“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, SVP and CSO, Pfizer Rare Disease Research Unit, said in a statement.
With the clinical setbacks to domagrozumab, Pfizer has one ongoing clinical trial in DMD—a Phase I study (NCT03362502) assessing the safety and tolerability of the 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 promotor. Twelve participants are expected to enroll in the study, whose primary outcome is incidence of dose-limiting safety or intolerability, as measured by treatment-related adverse events through one-year post-treatment.
Domagrozumab is a monoclonal antibody designed to work by blocking the activity of myostatin, a protein that acts in the body to prevent muscle from growing too large. Pfizer reasoned that domagrozumab could fight DMD by increasing muscle mass and function in patients with the disorder.
Domagrozumab was granted Orphan Drug designation in July 2012 and Fast Track Designation in November 2012 by the FDA. The European Medicines Agency (EMA) granted the investigational candidate Orphan Medical Product designation in February 2013.
Another DMD candidate developed to block myostatin is further in clinical development: Roche’s RG6206 (RO7239361) is now being assessed in a Phase II/III trial (NCT03039686). The treatment was renamed from BMS-986089 after Roche in-licensed the anti-myostatin adnectin fusion protein from Bristol-Myers Squibb (BMS) by agreeing to pay BMS $170 million upfront plus up to $205 million in milestones, as well as double-digit sales royalties.