BOULDER, Colo., June 16, 2026
Edgewise Therapeutics has announced positive top-line results from the 12-week Phase 2 CIRRUS-HCM trial evaluating EDG-7500, an investigational oral cardiac sarcomere modulator, in patients with both obstructive hypertrophic cardiomyopathy (oHCM) and nonobstructive hypertrophic cardiomyopathy (nHCM). The study demonstrated clinically meaningful improvements across key measures of cardiac function, biomarkers, symptoms, and quality of life while maintaining a favorable safety profile. Importantly, the company reported no meaningful reductions in left ventricular ejection fraction (LVEF) and no observed relationship between EDG-7500 exposure and systolic function, a finding that could differentiate the therapy from existing treatment approaches. The encouraging results support Edgewise’s plans to advance EDG-7500 into Phase 3 clinical development, with initiation targeted for the fourth quarter of 2026.
Phase 2 Trial Demonstrates Broad Clinical Benefits in HCM Patients
The multi-part CIRRUS-HCM trial enrolled patients with symptomatic obstructive and nonobstructive hypertrophic cardiomyopathy across more than 20 clinical sites in the United States. Part D of the study was specifically designed to evaluate dose optimization and inform Phase 3 development. Results showed that patients receiving EDG-7500 experienced substantial improvements in multiple clinically relevant endpoints. Among patients with obstructive HCM, 90% demonstrated improvements in left ventricular outflow tract gradient (LVOT-G) measurements, while 74% achieved normalization or at least a 50% reduction in NT-proBNP, a key biomarker associated with heart failure severity.
Significant improvements were also observed in patient-reported outcomes, including a 24-point increase in Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS) and meaningful gains in New York Heart Association (NYHA) functional class status. Similar benefits were reported in patients with nonobstructive HCM, where approximately 88% achieved NT-proBNP normalization or substantial reduction, accompanied by improvements in symptoms, exercise tolerance, and diastolic function. These findings suggest EDG-7500 may address a broad spectrum of disease manifestations across both major forms of hypertrophic cardiomyopathy.
Differentiated Cardiac Profile Preserves Systolic Function
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A key highlight of the Phase 2 data was the preservation of cardiac systolic function throughout treatment. Hypertrophic cardiomyopathy therapies that directly affect cardiac contractility can sometimes result in reductions in ejection fraction, creating concerns regarding heart failure risk. However, investigators reported that EDG-7500 demonstrated no meaningful changes in LVEF and no reductions below 50%, despite improvements in disease-related parameters. The therapy is designed to selectively slow early contraction velocity and improve impaired cardiac relaxation without compromising the heart’s pumping ability.
More than 700 echocardiograms conducted across healthy volunteers and HCM patients showed no relationship between drug concentration and systolic function measurements. Additionally, improvements in diastolic function markers, including increased early diastolic mitral annular velocity and reductions in E/e’ ratios, suggest that EDG-7500 may directly address the impaired cardiac relaxation that characterizes hypertrophic cardiomyopathy. This differentiated profile has generated significant interest among cardiology experts, particularly for patients with nonobstructive HCM where treatment options remain limited.
Advancement Toward Phase 3 Development and Future Treatment Potential
The favorable efficacy and safety findings position EDG-7500 as a promising candidate within the evolving hypertrophic cardiomyopathy treatment landscape. Hypertrophic cardiomyopathy affects approximately one in every 500 individuals worldwide and remains associated with reduced quality of life, heart failure progression, arrhythmias, and sudden cardiac death. Despite recent therapeutic advances, substantial unmet medical need persists, especially among patients with nonobstructive disease.
Edgewise Therapeutics believes the consistency of clinical benefits observed across biomarkers, echocardiographic parameters, symptoms, and functional status supports the continued development of EDG-7500 as a potentially differentiated therapy. With preparations underway for a pivotal Phase 3 program, the company aims to further evaluate the long-term efficacy and safety of EDG-7500 while exploring its potential to improve outcomes for patients living with this chronic and often debilitating cardiovascular condition.
Source: Edgewise Therapeutics press release
