Edgewise Therapeutics has reported positive top-line data from the 12-week Part D of the Phase II CIRRUS-HCM trial for its cardiac sarcomere modulator, EDG-7500, in patients with both obstructive hypertrophic cardiomyopathy (oHCM) and non-obstructive hypertrophic cardiomyopathy (nHCM).
The open-label, multi-part trial results showed EDG-7500 aimed to slow early contraction velocity and improve cardiac relaxation in symptomatic HCM, without affecting systolic function.
Go deeper with GlobalData
Discover B2B Marketing That Performs
Combine business intelligence and editorial excellence to reach engaged professionals across 36 leading media platforms.
More than 700 echocardiograms have indicated no observed effect on systolic function across different EDG-7500 concentrations.
The study included patients with both oHCM and nHCM. In Part D, which was designed to support a Phase III trial, dosing was determined by left ventricular outflow tract gradient (LVOT-G) for oHCM patients and by N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels for nHCM patients.
Across both groups, patients received doses ranging from 25mg to 150mg, and 53 participants, 20 with oHCM and 33 with nHCM, completed the 12-week regimen.
In oHCM patients, EDG-7500 resulted in broad clinical responses over key haemodynamic and biomarker measures.
Significant LVOT-G reductions were seen at rest and after Valsalva, with 90% of patients showing haemodynamic improvement. Approximately 74% achieved either NT-proBNP normalisation (<150pg/mL) or at least a 50% drop from baseline.
The Kansas City Cardiomyopathy Questionnaire score rose by 24 points on average, and 70% improved by at least one New York Heart Association (NYHA) functional class.
Early diastolic mitral annular velocity (e’ lateral) increased 20% and, in a high frame rate sub-study, the E/e’ ratio improved by 5.3 points.
Among nHCM participants, an average NT-proBNP reduction of 65% was noted, with 88% achieving normalisation or at least a 50% decrease.
The Kansas City Cardiomyopathy Questionnaire (KCCQ) score rose 13 points on average, and 64% improved in NYHA class. Early diastolic mitral annular velocity rose 37% while E/e’ improved 6.1 points in the sub-study.
EDG-7500 was generally well tolerated among the cohort, with adverse events mostly mild or moderate.
There were no notable changes in left ventricular ejection fraction (LVEF), nor were there cases with LVEF dipping below 50%. Two new instances (3.8%) of atrial fibrillation occurred, neither of which was attributed by investigators to EDG-7500.
Edgewise Therapeutics president and CEO Kevin Koch said: “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.
“These Phase II 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.”
The company expects to initiate a Phase III programme based on current CIRRUS-HCM data in the fourth quarter of 2026. The CIRRUS-HCM trial is ongoing at more than 20 clinical sites in the US.
