Edgewise Therapeutics’ EDG-7500 delivered positive Phase 2 CIRRUS-HCM results in obstructive and nonobstructive hypertrophic cardiomyopathy, showing broad improvements in cardiac function, biomarkers, and patient outcomes while preserving systolic function.
Written By: Kirti Kumbhar, M. Pharm (QA)
Reviewed By: Pharmacally Editorial Team
Edgewise Therapeutics reported positive top-line results from Part D of the Phase 2 CIRRUS-HCM study (NCT06347159) evaluating EDG-7500 in patients with obstructive (oHCM) and nonobstructive hypertrophic cardiomyopathy (nHCM). The 12-week study showed consistent improvements in cardiac function, biomarkers, symptoms, and functional status while preserving systolic function.
EDG-7500 is an investigational oral cardiac sarcomere modulator that slows early contraction velocity and improves impaired cardiac relaxation without causing meaningful reductions in left ventricular ejection fraction (LVEF). Across more than 700 echocardiograms performed in healthy volunteers and HCM patients, investigators observed no relationship between drug exposure and measures of systolic function.
About Hypertrophic Cardiomyopathy
Hypertrophic cardiomyopathy is the most common inherited heart disease, affecting approximately one in 500 people. The condition causes abnormal thickening of the heart muscle, leading to impaired relaxation, heart failure symptoms, arrhythmias, and an increased risk of sudden cardiac death. Despite recent therapeutic advances, significant unmet needs remain, particularly for patients with nonobstructive HCM.
Trial Design and Patient Cohorts
Part D enrolled 53 patients, including 20 with oHCM and 33 with nHCM, who received EDG-7500 doses ranging from 25 mg to 150 mg over 12 weeks. Dosing was guided by left ventricular outflow tract gradient (LVOT-G) in oHCM and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in nHCM. The study evaluated hemodynamic, biomarker, echocardiographic, and patient-reported outcomes.
Obstructive HCM Outcomes
Among patients with oHCM, EDG-7500 produced broad improvements across hemodynamic, biomarker, and clinical measures. Ninety percent of patients experienced reductions in LVOT-G, while 74% achieved NT-proBNP normalization or at least a 50% reduction from baseline.
Patients reported a mean 24-point improvement in Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS), while 70% improved by at least one New York Heart Association (NYHA) functional class. Echocardiographic assessments showed an approximately 20% increase in early diastolic mitral annular velocity (e’ lateral), a key marker of ventricular relaxation. In a high-frame-rate imaging substudy, E/e’ improved by a mean of 5.3 points, suggesting meaningful improvement in diastolic function and cardiac filling pressures.
Nonobstructive HCM Outcomes
Patients with nHCM demonstrated similarly encouraging results. NT-proBNP levels declined by approximately 65% on average, with 88% of patients achieving normalization or at least a 50% reduction from baseline.
KCCQ-OSS improved by a mean of 13 points, while 64% of patients improved by at least one NYHA functional class. Echocardiographic findings showed a 37% increase in e’ lateral, and the imaging substudy demonstrated a mean 6.1-point improvement in E/e’, supporting improved ventricular relaxation and filling.
Safety and Tolerability
EDG-7500 was generally well tolerated throughout the study. Most adverse events were mild to moderate in severity, and investigators identified no new safety signals.
Importantly, no meaningful changes in LVEF were observed, and no patient experienced an LVEF reduction below 50%. Two cases of new-onset atrial fibrillation occurred during the study, both of which investigators considered unrelated to treatment.
Regulatory and Clinical Outlook
Edgewise plans to advance EDG-7500 into Phase 3 development, with study initiation expected in the fourth quarter of 2026.
If confirmed in larger studies, EDG-7500 could offer a differentiated treatment option for both obstructive and nonobstructive HCM by improving diastolic function while preserving cardiac contractility. The data suggest EDG-7500 may offer a distinct approach within the emerging sarcomere modulator class by improving ventricular relaxation without the meaningful reductions in LVEF that have required monitoring with some therapies.
What This Means for Patients
For people living with hypertrophic cardiomyopathy, symptoms such as shortness of breath, fatigue, chest discomfort, dizziness, and exercise intolerance can significantly affect daily life. The Phase 2 CIRRUS-HCM results suggest that EDG-7500 may help improve heart relaxation, reduce disease-related stress on the heart, and improve symptoms and physical functioning in both obstructive and nonobstructive forms of HCM.
The treatment improved key measures of heart function without causing meaningful reductions in left ventricular ejection fraction (LVEF), a critical indicator of the heart’s pumping ability. While larger Phase 3 studies are needed to confirm these findings, EDG-7500 could represent a potential new treatment option for patients seeking symptom relief while preserving cardiac function.
Reference
About the Writer
Kirti Kumbhar (LinkedIn) is an M.Pharm graduate with experience in Quality Assurance at Lupin Limited and a strong interest in clinical research, regulatory affairs, and Trial Master File (TMF) management. She has developed knowledge of regulatory documentation, quality systems, compliance, and healthcare research through her professional experience. Passionate about clinical development and continuous learning, Kirti is committed to supporting high-quality healthcare documentation, regulatory excellence, and research-driven healthcare advancements.