Edgewise Therapeutics announces top-line data of EDG-7500

Edgewise Therapeutics announced top-line data of EDG-7500 from the Phase 1 trial in healthy subjects and the single-dose arm of the Phase 2 CIRRUS-HCM trial in patients with obstructive HCM. EDG-7500 is a novel oral, selective, cardiac sarcomere modulator, specifically designed to slow early contraction velocity and address impaired cardiac relaxation associated with HCM. In the placebo-controlled Phase 1 single ascending dose, or SAD, trial, healthy subjects received single doses of EDG-7500, ranging from 5 to 300 mg. In the multiple ascending dose, or MAD, portion of the trial, healthy subjects received 25 to 100 mg once daily for 14 days. EDG-7500 was well tolerated in both the SAD and MAD; there were no clinically meaningful changes or trends in vital signs, clinical chemistry, hematology, or electrocardiograms. There were no meaningful changes in LVEF for all SAD and MAD subjects across a broad range of EDG-7500 exposures. In the MAD, a half-life of approximately 30 hours was observed, and steady state was achieved in approximately 4 days after the start of once-daily dosing. Generally, dose proportional increases in exposure were observed in both SAD and MAD. In CIRRUS-HCM Part A, patients with obstructive HCM received a single dose of 50, 100 or 200 mg of EDG-7500. A 67% mean reduction in resting LVOT pressure gradient and a 55% mean reduction in provokable LVOT-G were observed in patients receiving the 100 and 200 mg single doses. LVOT gradients less than 30 mmHg at rest and less than 50 mmHg with Valsalva were observed in 60% of patients receiving 100 or 200 mg of EDG-7500. Importantly, gradient reduction was achieved without a meaningful change in LVEF. Treatment with a single dose of EDG-7500 also led to a 64% mean reduction in NT-proBNP, a key biomarker of heart failure, in the 200 mg cohort. This reduction highlights the potential of our mechanism in the treatment of diseases of diastolic dysfunction, including non-obstructive HCM. Across the Phase 1 and CIRRUS-HCM trials, no subjects had a LVEF reduction to below 50% across a broad range of EDG-7500 exposures.