Edgewise Therapeutics' hypertrophic cardiomyopathy (HCM) asset has resulted in “rapid and clinically meaningful” reductions of a measure of obstruction of the heart’s valves.
The biotech has been evaluating 50-mg and 100-mg daily doses of its cardiac sarcomere modulator, dubbed EDG-7500, in a four-week, open-label phase 2 Cirrus-HCM trial of patients with obstructive or nonobstructive HCM, a disease in which the heart muscle becomes thickened.
Should EDG-7500 eventually make it to market, the drug will find itself competing with Bristol Myers Squibb’s established Camzyos and Cytokinetics’ candidate aficamten, which has been submitted to the FDA for approval and has a PDUFA date of Sept. 26.
The latest slice of data shows that among patients with obstructive HCM—where the thickening affects the amount of blood pumped out of the heart—a 100-mg dose resulted in a mean reduction from baseline of 71% of left ventricular outflow tract gradient (LVOT-G) when resting and 58% after forced exhalation. LVOT-G measures the difference in pressure between the heart’s left ventricle and aorta.
This reduction in pressure was achieved without a meaningful change in left ventricular ejection fraction (LVEF), Edgewise noted, meaning that the left ventricle of the heart was still pumping a normal amount of blood.
In addition, the 100-mg cohort also saw a 62% mean reduction from baseline in NT-proBNP, a biomarker of heart failure.
In participants with nonobstructive HCM, 100 mg of EDG-7500 administration resulted in a 42% reduction in NT-proBNP.
Across the study, two patients experienced “serious adverse events of atrial fibrillation (AF) requiring cardioversion,” Edgewise said. The rates of AF—a term for irregular heart rhythm—were in the range of those seen in phase 2 trials of cardiac myosin inhibitors, according to the biotech.
Overall, the most frequently reported adverse events in the trial were dizziness, upper respiratory tract infection and AF, with “nearly all” of these events “considered mild to moderate in severity.” Camzyos comes with an FDA black box warning of heart failure.
“Building on the strength of clinical data to date, we are optimizing our dosing strategy in part D of CIRRUS-HCM in participants with obstructive and nonobstructive HCM, which will inform our plans for phase 3,” Edgewise’s CEO Kevin Koch, Ph.D., said in the April 2 release.
“We believe EDG-7500, which delivered clinically meaningful results without causing systolic dysfunction, has the potential to be a significant advancement for patients with HCM and the clinicians who care for them,” Koch added.
The latest data drop follows an earlier readout from the study last September that hit key biomarkers.
Initial data from the final part of the study are expected in the second half of the year, with Edgeiwse penciling in a phase 3 trial launch in the first half of 2026.
Edgewise aligned this morning’s news with a $200 million underwritten offering of common stock. The biotech has earmarked the funds to support the hoped-for launch of its Becker muscular dystrophy drug sevasemten, as well as the phase 3 trial of EDG-7500.
The biotech was down 28% in premarket trading Wednesday morning after announcing its offering.