Preventing Duchenne Muscular Dystrophy Cardiomyopathy Through Antagonism of the Thromboxane Prostanoid Receptor: An FDA Funded Phase 2 Clinical Trial


Clinical Trials

Poster Number: Virtual


Ines Macias-Perez, PhD, Cumberland Pharmaceuticals, Larry Markham, MD, Riley Childrens Hospital, James West, PhD, Vanderbilt University, Ingrid Anderson, PhD, CCRP, Cumberland Pharmaceuticals, Inc

Duchenne muscular dystrophy (DMD) is a rare and fatal disease with no cure. Cardiomyopathy (CM) is the leading cause of death. Thromboxane prostanoid receptor (TPr) activation increases calcium transients in cardiomyocytes, causes arrhythmia, & is pro-fibrotic. We thus hypothesized TPr activation contributes to DMD CM & blockade with the TPr antagonist iferoban may prevent the cardiac phenotype in DMD animal models. Three transgenic mouse models of MD (mdx/utrn double knockout (DKO), 2nd gen mdx/mTR DKO, & delta-sarcoglycan (dSG) KO) demonstrated 100% survival of ifetroban-treated mice, compared with 60%, 43%, & 90% survival for DKO, mdx/mTR, & dSG KO mice, respectively. Ifetroban improved cardiac output in DKO & mdx/mTR mice, & normalized fractional shortening, ejection fraction, & other parameters in dSG KO mice. These preclinical findings informed the currently enrolling multicenter, randomized, controlled phase 2 trial to determine the safety and efficacy of oral ifetroban in DMD CM. Our clinical trial is evaluating two doses of daily, oral ifetroban for its potential cardioprotective effect in 48 DMD subjects: 24 with early CM (LVEF > 45%) and 24 with advance CM (LVEF 35-45%). Eligible patients will receive 12 months of treatment and upon completion, may participate in the optional open-label extension. A safety review was completed after 12 subjects completed 6 months of treatment and an interim analysis of efficacy is in progress after 24 subjects completed their Month 6 visit. The measurable effect of oral ifetroban on cardiac and respiratory outcomes, muscle strength, daily activity and quality-of-life was investigated in DMD patients 7 years of age or older will be reported. This is the first DMD clinical trial awarded an FDA grant to study an orphan product.