CIRRUS-HCM: EDG-7500 Improves LVOT, NYHA Class in oHCM and nHCM

EDG-7500 has displayed clinically meaningful improvements in patients with hypertrophic cardiomyopathy (HCM) after 12 weeks, according to results from the CIRRUS-HCM trial.1

These data were presented at the European Society of Cardiology (ESC) Congress 2026 in Munich, Germany, by Anjali Owens, MD, a cardiovascular fellow at the Hospital of the University of Pennsylvania.1

“The totality of the Phase 2 efficacy and tolerability data continues to support a differentiated profile for EDG-7500 across HCM,” Matthew Martinez, MD, president of the HCM Society, said in a statement. “What is especially encouraging is the consistency of symptom and functional improvement across dose levels without evidence of systolic liability or heart failure risk.”2

EDG-7500 is a novel cardiac sarcomere modulator in development by Edgewise Therapeutics, Inc., for hypertrophic cardiomyopathy (HCM). Preclinical models have shown increases in early diastolic relaxation while maintaining myosin availability, as well as reductions in LVOT gradients and preservation of net systolic function. However, no meaningful reductions in left ventricular ejection fraction (LVEF) have been shown in the EDG-7500 program prior to this trial.1

CIRRUS-HCM is an ongoing open-label study conducted across 17 locations in the US. Patients were eligible for inclusion if they were ≥18 to <85 years of age and were diagnosed with HCM at the time of screening. Additionally, patients were required to have an LVOT peak gradient ≥50 mmHg measured at rest or during the Valsalva maneuver, or LVOT peak gradient <30 mmHg measured at rest and <50 mmHg during the Valsalva maneuver, among other criteria. Patients who had undergone invasive septal reduction therapy, had obstructive coronary artery disease, or a documented history of myocardial infarction, among other criteria, were excluded.3

Patients were randomly assigned to 1 of 4 experimental groups: the first group, Part A, received a single dose of EDG-7500; Part B included patients with obstructive HCM who received EDG-7500 once daily for ≤28 days; Part C included patients with nonobstructive HCM and received EDG-7500 once daily; and Part D received EDG-7500 for ≤24 months. Part D included both new participants and patients who had completed part B or C.3

CIRRUS’s primary outcome is incidence of treatment-emergent adverse events from screening through study completion – for Part A, this period is ≤38 days, while Part B and C were ≤73 days and Part D was ≤18 months. Secondary outcomes included change from baseline in LVOT gradient, pharmacokinetic parameters of EDG-7500, and change from baseline in cardiac biomarkers.3

The presentation at ESC 2026 was a 12-week evaluation of the drug’s safety and efficacy. By 12 weeks, Owens and colleagues did not find any clinically meaningful change in LVEF. No patients exhibited reductions in LVEF to <50%, and no correlation was observed between EDG-7500 treatment and LVEF change. Additionally, patients with obstructive HCM did exhibit substantial reductions in LVOT gradient by 12 weeks, with Valsalva measurements falling by 51% from baseline and resting LVOT gradient falling by 55%. NT-proBNP exhibited a geometric mean decrease of 56% from baseline, while Hs-cTnl dropped by 40% from baseline.1

Patients with obstructive HCM also displayed sustained improvements in New York Heart Association (NYHA) Class, with 70% of patients improving by ≥1 NYHA class by week 12 and 50% of patients in NYHA Class III improving to Class I by week 12. Patients with nonobstructive HCM also saw substantial improvements in NYHA class, with 29% in Class III improving to Class I and 64% of patients improving by ≥1 NYHA class at week 12. EDG-7500 also exhibited no LVEF <50% during these 12 weeks while remaining well-tolerated with 2 severe adverse treatment events, 1 of which was determined to be unrelated to treatment.1

Ultimately, Owens and colleagues concluded that EDG-7500 has performed well in both disease populations over the 12 months of treatment thus far. In the presentation, Owens announced that phase 3 trials of EDG-7500 are on track to initiate by Q4 2026.1

“From the outset, our goal was to identify a cardiovascular therapy with a profile that avoids the liability of the CMI class, with EDG-7500 emerging from that effort,” Kevin Koch, PhD, president and chief executive officer of Edgewise Therapeutics, said in a statement. “These Phase 2 data mark an important milestone for Edgewise and the HCM community, reinforcing EDG-7500’s unique approach with the potential to address diastolic dysfunction across HCM without meaningful impact on LVEF.”2

References

1. Owens A. CIRRUS-HCM: 12-Week Evaluation of the Safety and Efficacy of the Novel Cardiac Sarcomere Modulator EDG-7500 in Nonobstructive and Obstructive Hypertrophic Cardiomyopathy. Presented at the European Society of Cardiology (ESC) Congress 2026, Munich, Germany. August 28-31, 2026.

2. Edgewise Therapeutics. Edgewise Therapeutics Announces Positive Top-Line Data from 12-Week Phase 2 CIRRUS-HCM Trial with EDG-7500 in Obstructive and Nonobstructive Hypertrophic Cardiomyopathy (HCM). PR Newswire. June 16, 2026. Accessed September 14, 2026. https://www.prnewswire.com/news-releases/edgewise-therapeutics-announces-positive-top-line-data-from-12-week-phase-2-cirrus-hcm-trial-with-edg-7500-in-obstructive-and-nonobstructive-hypertrophic-cardiomyopathy-hcm-302801108.html

3. Edgewise Therapeutics, Inc. A Study of EDG-7500 in Adults With Hypertrophic Cardiomyopathy (CIRRUS-HCM). ClinicalTrials.gov Identifier: NCT06347159. Updated July 31, 2026. Accessed September 11, 2026. https://clinicaltrials.gov/study/NCT06347159