Cumberland Pharmaceuticals' ifetroban, a novel oral thromboxane receptor antagonist, has shown promising results in improving heart function in patients with Duchenne muscular dystrophy (DMD). The Phase 2 FIGHT DMD trial (NCT03340675) demonstrated a statistically significant improvement in left ventricular ejection fraction (LVEF) in patients treated with ifetroban, offering hope for a targeted therapy to address cardiac complications associated with DMD, the leading cause of mortality in this patient population.
The FIGHT DMD trial, a 12-month, double-blind, randomized, placebo-controlled study, enrolled 41 patients with DMD. Participants were administered either high-dose ifetroban (300 mg per day), low-dose ifetroban (150 mg per day), or a placebo. The primary endpoint was the change in LVEF over the treatment period.
Significant Improvement in Cardiac Function
Results from the trial indicated that patients receiving high-dose ifetroban experienced a 3.3% improvement in LVEF overall. Specifically, the high-dose ifetroban group showed a 1.8% increase in LVEF, while the placebo group exhibited an expected 1.5% decline. This improvement was even more pronounced when compared to propensity-matched natural history controls, where the high-dose ifetroban group demonstrated a significant 5.4% overall improvement in LVEF compared to a 3.6% decline in the control group.
"These results represent a significant milestone in DMD cardiomyopathy," said Larry W. Markham, MD, professor of Pediatrics and Medicine, Indiana University School of Medicine, Division Chief of Pediatric Cardiology at Riley Children's Hospital and Principal Investigator of the FIGHT DMD trial. "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."
Addressing an Unmet Need in DMD
DMD is a rare and incurable genetic disorder affecting approximately 1 in every 3,300 male births worldwide. Characterized by progressive muscle weakness, DMD leads to cardiomyopathy, which is the primary cause of death in these patients. Current treatment options primarily focus on managing symptoms and delaying disease progression, but no therapies are specifically approved for DMD-related heart disease.
Ifetroban, which has received both Orphan Drug Designation and Rare Pediatric Disease Designation from the FDA, acts as a potent and selective thromboxane-prostanoid receptor (TPr) antagonist. By blocking the thromboxane receptor, ifetroban aims to reduce inflammation and fibrosis, key factors contributing to cardiac dysfunction in DMD. The drug was well-tolerated in both treatment groups, with no serious drug-related adverse events reported.
Future Directions for Ifetroban
Cumberland Pharmaceuticals plans to conduct further data analysis and complete a full study report in preparation for a meeting with the FDA to discuss the next steps for ifetroban's development and potential commercialization. If approved, ifetroban would be the first therapy specifically indicated for DMD-related heart disease, addressing a critical unmet medical need. The company is also evaluating ifetroban for systemic sclerosis and pulmonary fibrosis, with an ongoing Phase 2 trial (FIGHTING FIBROSIS Trial) in patients with idiopathic pulmonary fibrosis (IPF).
