A data release from Colorado-based Edgewise Therapeutics (Nasdaq: EWTX) for pipeline candidate EDG-7500 in hypertrophic cardiomyopathy (HCM) suggest a potentially differentiated approach in a disease area currently dominated by cardiac myosin inhibitors. The company reported positive 12-week top-line data from Part D of the CIRRUS-HCM trial on June 16, showing improvements in hemodynamics, cardiac biomarkers, and patient-reported outcomes in both obstructive and nonobstructive HCM (nHCM), while no patient experienced a reduction in left ventricular ejection fraction (LVEF) below 50%.
The findings are particularly notable in nHCM, where no pharmacological therapy has yet received regulatory approval. Unlike approved cardiac myosin inhibitors, EDG-7500 is designed to slow early contraction velocity and improve diastolic relaxation without directly suppressing contractility, potentially avoiding the systolic dysfunction that has limited the class.
Part D enrolled 53 patients across more than 20 US sites, including 20 patients with obstructive HCM and 33 with nHCM. Patients received individualized doses ranging from 25 mg to 150 mg daily. The open-label design and small sample size limit interpretation of efficacy results.
Among obstructive HCM patients, 90% demonstrated improvement in hemodynamic measures, including reductions in left ventricular outflow tract gradient. Seventy-four percent achieved either normalization of NT-proBNP or a reduction of at least 50% from baseline.
In nHCM, EDG-7500 produced an approximately 65% mean reduction in NT-proBNP, while 88% of patients achieved normalization or a ≥50% reduction from baseline. Kansas City Cardiomyopathy Questionnaire Overall Summary Score improved by a mean of 13 points, and 64% of patients improved by at least one New York Heart Association functional class. Measures of diastolic function also improved.
Safety was consistent with prior studies. No patient experienced an LVEF reduction below 50%, and adverse events were predominantly mild to moderate. Two patients developed atrial fibrillation, both considered unrelated to treatment.