Ifetroban continues to show cardiac protection in Phase 2 DMD trial
Developer plans to pursue regulatory approval once analyses are complete
Ifetroban, Cumberland Pharmaceuticals’ investigational oral therapy, improved heart function and reduced cardiac damage biomarkers in people with Duchenne muscular dystrophy (DMD), according to new trial data.
These findings from the Phase 2 FIGHT DMD trial (NCT03340675) were presented at the Parent Project Muscular Dystrophy (PPMD) annual conference, held recently in Las Vegas.
Long-term safety and efficacy data are expected later this year. Cumberland plans to discuss a path toward regulatory approval with the U.S. Food and Drug Administration (FDA) once all analyses are completed.
“These new results reinforce our conviction that ifetroban has the potential to address the leading cause of death in DMD patients,” A.J. Kazimi, Cumberland’s CEO, said in a company press release. “We’re optimistic about taking the next steps toward bringing this much-needed treatment to DMD patients and their families.”
Ifetroban boosts heart health by reducing inflammation, scarring
People with DMD experience progressive muscle damage because they lack dystrophin, a protein that helps safeguard muscles against injury. The cardiac muscles that are responsible for pumping blood are often affected, leading to heart problems. There aren’t any approved therapies specifically for treating heart disease in DMD.
Ifetroban is a once-daily oral medication that works to boost heart health by reducing the cardiac inflammation and scarring (fibrosis) that contribute to heart dysfunction. It does so by blocking a protein involved in these processes called the thromboxane receptor.
The therapy has been studied for the treatment of various diseases, and has been shown to protect against heart disease in preclinical models of severe DMD.
Ifetroban has received orphan drug and rare pediatric disease designations from the FDA for treating DMD heart disease. These designations are intended to expedite the therapy’s clinical development.
Trial funded by $1 million FDA grant
The FIGHT DMD trial, funded by a $1 million grant from the FDA, enrolled 41 males with DMD, ages 7 and older. They were randomly assigned to receive one of two doses of ifetroban (100 mg or 300 mg) or a placebo once daily for about a year.
Previously reported top-line trial results showed ifetroban led to clinically meaningful improvements in heart function, meeting the study’s main goal.
Specifically, ifetroban was associated with a significant, 3.3% improvement in left ventricle ejection fraction (LVEF) — an indicator of how well the heart pumps out blood with each heartbeat — compared with the placebo.
While LVEF worsened by an average of 1.5% with the placebo, consistent with the expected declines in heart function that occur with DMD progression, the same cardiac measure improved by 1.8% with ifetroban.
When combining the placebo group with an external group of matched, untreated DMD patients from a natural history study, a 3.6% decline in LVEF was observed, amounting to a 5.4% relative improvement with ifetroban.
All participants in main trial opt into open-label extension
The recent presentation also demonstrated that ifetroban at its higher dose was associated with reductions in blood levels of cardiac damage biomarkers, including NT-proBNP and cardiac troponin 1. These markers increased in the placebo group.
“The improvement in heart function observed, combined with the reduction in cardiac damage markers, suggests we may be able to meaningfully impact the progressive heart disease that affects virtually all DMD patients,” Kazimi said.
The CEO noted that functional and biochemical improvements are “exactly what you’d want to see in a therapy designed to protect the heart.”
Ifetroban was well tolerated, with no serious adverse events related to the medication.
Seeing these promising results validates our belief that targeted heart therapies can make a meaningful difference for our children. This trial represents what’s possible when families refuse to accept the status quo and invest in advancing medical research.
Although the 300 mg dose of ifetroban is higher than what’s been used in other contexts, the medication reaches lower levels in the bloodstream in people with DMD. Pharmacological and safety data indicated the treatment did not accumulate to unsafe levels.
All participants who completed the main trial opted to continue in an open-label extension, where they are receiving the high dose ifetroban for up to three years.
“Seeing these promising results validates our belief that targeted heart therapies can make a meaningful difference for our children,” said Terry Marlin, president and founder of Fight DMD, a community-based nonprofit aimed at advancing DMD research. “This trial represents what’s possible when families refuse to accept the status quo and invest in advancing medical research.”
Fight DMD provided funding for the preclinical studies that supported the launch of the Phase 2 trial, which was subsequently named in honor of the organization. The Marlin family also gave input into the study’s design and contributed personal photos for its patient brochure.
“We’re deeply grateful to both Terry Marlin and [Fight DMD] for their early vision and funding, and to PPMD for their [long-standing] support and partnership throughout this journey – as both organizations have been instrumental in making this breakthrough possible,” Kazimi said.
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