Phase 2 trial shows DMD treatment ifetroban boosts heart function
Top-line results are 'significant milestone,' trial investigator says
Treatment with oral therapy ifetroban led to improvements in measures of heart function in people with Duchenne muscular dystrophy (DMD), according to top-line results from a clinical trial.
The “impressive results” are a “pivotal moment” for developer Cumberland Pharmaceuticals, “and, more importantly, for the DMD community,” A.J. Kazimi, CEO of Cumberland, said in a company press release.
The Phase 2 study, FIGHT DMD (NCT03340675), enrolled 41 male patients with DMD ages 7 and older. Participants were randomly assigned to receive one of two doses of ifetroban (150 mg or 300 mg per day), or a placebo, for about a year.
The study’s main goal was to evaluate the effect of treatment on left ventricle ejection fraction (LVEF), a measure of how well the heart pumps blood out to the body with each heartbeat. In patients given the higher dose of ifetroban, LVEF improved by an average of 1.8% over the course of the study. In patients given a placebo, LVEF worsened by 1.5%, in line with the expected decline of heart function as DMD progresses.
“These results represent a significant milestone in DMD [heart disease],” said Larry W. Markham, MD, principal investigator of the FIGHT DMD trial and a professor at Indiana University School of Medicine. “We are seeing evidence that there is an opportunity to potentially alter the course of heart disease in DMD patients. The improvement in cardiac function observed with ifetroban, particularly in the high-dose group, offers hope for these patients and their families.”
Results in ‘stark contrast’ to expected heart-function decline
A comparison against matched data from natural history studies, which track the progression of DMD in the absence of treatment, likewise suggested that ifetroban improved heart function. In the natural history data, LVEF worsened by 3.6% over the course of a year.
“The preservation and even improvement in cardiac function seen with ifetroban treatment stands in stark contrast to the expected decline we typically observe in untreated DMD patients,” said Jonathan Soslow, MD, a pediatric cardiologist and professor at Vanderbilt University.
Safety data from the study indicated that ifetroban was generally well tolerated, with no serious drug-related side effects reported with either dose.
“This trial represents hope for our Duchenne community,” said Pat Furlong, president and CEO of Parent Project Muscular Dystrophy. “Heart disease remains one of the most devastating aspects of Duchenne, and these results suggest we may finally have a therapeutic option that could make a meaningful difference in the lives of patients and families.”
Cumberland plans to meet with the U.S. Food and Drug Administration (FDA) to discuss next steps for the treatment’s development.
DMD is a genetic disorder in which the body is unable to make dystrophin, a protein that normally helps to protect muscles from damage. This leads to progressive damage to skeletal muscles, which move the body around, as well as the cardiac muscles in the heart that are responsible for pumping blood. DMD patients often develop heart problems, but there are no approved therapies that specifically target heart issues in DMD.
Ifetroban aims to improve heart health by reducing inflammation and scarring (fibrosis) in the heart. The therapy works to block the activity of a protein called the thromboxane receptor, which is involved in driving heart fibrosis.
The FIGHT DMD trial was funded by a $1 million FDA grant, part of the FDA’s orphan products grants program. Cumberland was the first company to receive this type of funding to advance a DMD treatment.
“As the first company to receive FDA Orphan Products Development funding for a DMD clinical trial, we’re honored to be advancing a potential breakthrough therapy for DMD-related heart disease,” Kazimi said. The trial results “validate our commitment to developing innovative treatments for rare diseases and underscore the importance of collaborative partnerships between industry, academia, and regulatory agencies in addressing critical unmet medical needs,” he said.
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