Edgewise Submits EDG-7500 Phase 3 Protocol After FDA Meeting

Edgewise Therapeutics has advanced the clinical development of EDG-7500, its investigational treatment for hypertrophic cardiomyopathy (HCM), following a productive End-of-Phase 2 meeting with the U.S. Food and Drug Administration (FDA). The company has submitted the protocol for its planned Phase 3 STRATUS-HCM trial, incorporating a tolerability-based dose-escalation strategy that does not require echocardiographic monitoring to guide dose increases. The trial is expected to begin in the fourth quarter of 2026.

The proposed approach represents an important feature of the Phase 3 programme, particularly because it allows investigators to determine dose escalation based on patients’ tolerability rather than relying on echocardiographic measurements for these decisions.

FDA Feedback Supports the Proposed Phase 3 Design

During the End-of-Phase 2 meeting, Edgewise presented data from its ongoing Phase 2 CIRRUS-HCM study (NCT06347159) and discussed the proposed STRATUS-HCM design with the FDA. Following receipt of the meeting minutes, the company submitted the Phase 3 protocol, incorporating the study design, clinical assessments and proposed dose-escalation approach.

Under the protocol, participants will initially receive EDG-7500 at 50 mg once daily. The dose may increase to 100 mg after four weeks and subsequently to 150 mg after another four weeks, provided investigators determine that the preceding dose is well tolerated.

Importantly, the proposed echo-independent approach applies specifically to dose-escalation decisions rather than eliminating echocardiographic assessments from the study. Echocardiograms will remain scheduled at baseline, Week 12 and the end of treatment at Week 24 to evaluate secondary efficacy measures, including aspects of diastolic function.

Edgewise also reported that feedback from the European Medicines Agency (EMA) and Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) was generally consistent with the proposed dosing approach.

STRATUS-HCM to Evaluate Obstructive and Nonobstructive HCM

STRATUS-HCM is planned as a global, randomized, double-blind, placebo-controlled Phase 3 programme involving approximately 600 adults with symptomatic HCM. The programme will comprise two independent studies under a single master protocol: approximately 200 participants with obstructive HCM and 400 with nonobstructive HCM.

The two populations will be randomized separately and evaluated independently for safety and efficacy. Participants will receive EDG-7500 or placebo in a 2:1 ratio for 24 weeks, followed by a direct transition into a long-term extension study. The protocol also allows the sample size to increase based on interim evidence of efficacy.

The primary endpoint is the change from baseline in peak oxygen consumption (peak VO₂) at Week 24, an objective measure of exercise capacity. Secondary endpoints include New York Heart Association (NYHA) functional class, the Kansas City Cardiomyopathy Questionnaire (KCCQ) and, specifically for participants with obstructive HCM, left ventricular outflow tract gradient (LVOT-G).

The separate evaluation of obstructive and nonobstructive HCM is clinically relevant because both forms involve abnormal cardiac muscle structure and function but present different haemodynamic characteristics. Assessing them independently will allow the programme to evaluate EDG-7500 across both populations without treating them as a single clinically uniform group.

EDG-7500 Targets Cardiac Sarcomere Function

EDG-7500 is an oral, first-in-class cardiac sarcomere modulator designed to act on the regulatory light chain. The investigational drug is intended to slow early cardiac contraction velocity and improve impaired relaxation of the heart muscle.

HCM is the most common form of genetic heart disease, affecting approximately one in 500 people. It is characterized by thickening of the left ventricular wall, which can impair the heart’s ability to relax and fill with blood. Patients may experience breathlessness, chest pain, fatigue, dizziness, fainting and irregular heart rhythms.

The condition occurs in obstructive and nonobstructive forms, with treatment needs influenced by the underlying cardiac abnormalities and clinical presentation.

Phase 3 Will Establish the Clinical Value of the Dosing Strategy

The STRATUS-HCM programme will evaluate whether EDG-7500 can improve exercise capacity and other clinical measures in patients with both forms of symptomatic HCM. Its tolerability-based dose-escalation approach may simplify treatment titration by removing the need for echocardiograms specifically to guide dose increases. However, scheduled cardiac imaging remains part of the protocol.

The larger clinical question is whether modulation of cardiac sarcomere function can translate into meaningful improvements in exercise capacity and patient-reported health outcomes across obstructive and nonobstructive HCM.

With the Phase 3 protocol now submitted following discussions with the FDA, Edgewise is progressing EDG-7500 towards a pivotal evaluation. The planned STRATUS-HCM studies will need to establish the investigational drug’s safety, efficacy and clinical benefit before its potential role in HCM treatment can be determined.

 Reference

Edgewise Therapeutics Announces Productive End-of-Phase 2 Meeting with FDA for EDG-7500 in HCM; Phase 3 Protocol Features Tolerability-Based Dose Escalation Without Safety Echo Monitoring, Edgewise, 05 November 2026