Edgewise Therapeutics announces positive top-line results from Phase 2 CIRRUS-HCM trial of EDG-7500 in hypertrophic cardiomyopathy

Edgewise Therapeutics reported encouraging top-line results from its Phase 2 CIRRUS-HCM four-week study evaluating EDG-7500 in patients with both obstructive and nonobstructive hypertrophic cardiomyopathy (HCM). EDG-7500 is a novel, oral cardiac sarcomere modulator designed to slow early contraction velocity and improve impaired cardiac relaxation without compromising systolic function.

In participants with obstructive HCM, the 100 mg dose of EDG-7500 achieved a 71% mean reduction in resting left ventricular outflow tract gradient (LVOT-G) and a 58% reduction post-Valsalva, with no meaningful declines in left ventricular ejection fraction (LVEF). The treatment also led to a 62% mean reduction in NT-proBNP, a key heart failure biomarker, and a 23-point average improvement on the Kansas City Cardiomyopathy Questionnaire (KCCQ). Furthermore, 78% of participants improved by at least one NYHA class, and 67% reached Class I (asymptomatic).

Among nonobstructive HCM participants, EDG-7500 demonstrated a 42% reduction in NT-proBNP, early improvements in diastolic function, and strong gains on KCCQ scores.

EDG-7500 was generally well-tolerated. The most frequent adverse events were dizziness, upper respiratory tract infections, and atrial fibrillation (AF). Two participants required cardioversion for AF, and one discontinued due to moderate dizziness. No cases of LVEF below 50% were observed.

Part D of CIRRUS-HCM, a 12-week dosing study with dose optimization, is underway, with data expected in the second half of 2025. A Phase 3 trial is planned for the first half of 2026.