Edgewise Therapeutics has announced encouraging results from its ongoing Phase 2 CIRRUS-HCM trial of EDG-7500, a novel oral cardiac sarcomere modulator aimed at improving heart relaxation in hypertrophic cardiomyopathy (HCM) without affecting systolic function.

 

CIRRUS-HCM, an open-label, multi-part study, evaluates EDG-7500 in patients with obstructive and nonobstructive HCM. Earlier this year, the company reported positive top-line results from Parts B and C, showing improvements in key HCM markers including NT-proBNP, KCCQ scores, NYHA class, and LVOT gradients in obstructive patients. 

 

"EDG-7500 administration led to KCCQ score improvements that appeared favorable relative to those reported in other cardiovascular trials, including those with cardiac myosin inhibitors," the company noted.

 

Now, new data from lower-dose cohorts (25 mg) reinforce EDG-7500’s clinical activity across HCM markers while maintaining a strong safety profile. No participants experienced clinically meaningful drops in left ventricular ejection fraction (LVEF), reductions below 50%, or atrial fibrillation. Across all Part B and C cohorts, 43 participants completed dosing.

 

Part D of CIRRUS-HCM is exploring dose optimization and biomarker-guided treatment to inform Phase 3 development. Screening is complete, with over 40 participants enrolled. By the December 23 data cutoff, roughly 70% had reached doses of 100 mg or higher. Interim safety data from 20 participants completing 12 weeks of dosing show EDG-7500 remains well-tolerated, with no significant LVEF changes—continuing a differentiated profile versus cardiac myosin inhibitors.

 

"Unlike CMIs, which have a mechanism of action that has been associated with a risk of systolic dysfunction and an increased risk of heart failure, EDG-7500 administration continues to present no meaningful effect on LVEF," the company emphasized, noting that this preservation of systolic function could broaden patient access if approved.

 

Kevin Koch, President and CEO of Edgewise Therapeutics, said, "I'm excited about the advances we've made in Part D of the CIRRUS-HCM trial, where we've exceeded our year-end enrollment goal, highlighting continued enthusiasm for the program from patients and physicians. 

 

"I'm especially pleased with EDG-7500's safety profile to date, and the lack of clinically relevant drops in ejection fraction, or any ejection fraction drops below 50%. A major focus of 2026 will be refining our development strategy to deliver the best-in-disease therapeutic profile that EDG-7500 may offer to obstructive and nonobstructive HCM patients."