Edgewise Therapeutics Begins Phase 2 Trial of EDG-7500 in Obstructive HCM

Edgewise Therapeutics Inc., a prominent biopharmaceutical company specializing in muscle disease, has recently initiated the Phase 2 CIRRUS-HCM trial for their drug candidate, EDG-7500. This trial marks a significant step in the development of therapies targeting hypertrophic cardiomyopathy (HCM), a genetic heart condition affecting numerous individuals.

EDG-7500 is an innovative, orally administered, selective cardiac sarcomere modulator designed to address cardiac relaxation issues and slow early contraction velocity, particularly in diseases associated with diastolic dysfunction such as HCM. The Phase 2 CIRRUS-HCM trial aims to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of EDG-7500 in patients suffering from obstructive HCM. The trial is divided into two parts: Part A, which will assess single doses, and Part B, which will evaluate multiple doses over a 28-day period.

Dr. Marc Semigran, Chief Development Officer at Edgewise Therapeutics, expressed optimism regarding the advancement of EDG-7500, citing promising preclinical data that demonstrated significant relief in left ventricular (LV) outflow tract gradients while maintaining normal LV contractility. Moreover, EDG-7500 showed improvements in ventricular filling and diastolic function in preclinical models of non-obstructive HCM.

Kevin Koch, President and CEO of Edgewise Therapeutics, emphasized the milestone this trial represents for the company. He highlighted EDG-7500 as a testament to their robust discovery and development capabilities and their dedication to addressing serious muscle diseases.

Edgewise Therapeutics has scheduled the release of data from the single dose arm of this trial and a Phase 1 trial involving healthy volunteers for the third quarter of 2024. Additionally, they plan to initiate a 28-day trial for both obstructive and non-obstructive HCM patients in the latter half of 2024, followed by an open-label extension trial in the fourth quarter of the same year.

The CIRRUS-HCM trial is a multi-center, two-part, open-label study conducted at up to 20 clinical sites across the United States. It aims to include up to 30 adult patients with obstructive HCM. These participants will receive single and potentially multiple oral doses of EDG-7500 over a 28-day period.

Hypertrophic cardiomyopathy is the most prevalent genetic heart disease, impacting approximately one in every 200-500 individuals. This condition is characterized by abnormal cardiac proteins, such as cardiac myosin, causing excessive heart contraction or hypercontractility. This excessive contraction results in increased stress and thickening of the LV walls, thereby reducing its compliance and efficiency in pumping blood. Patients with HCM often face severe limitations in their daily activities and are at heightened risk of heart failure, stroke, atrial fibrillation, and sudden cardiac arrest. Despite advancements in treatment, a significant unmet need for new therapeutic options remains.

EDG-7500, with its selective modulation of cardiac sarcomeres, offers a potential new approach for HCM treatment. It aims to slow down the early contraction velocity, thereby improving cardiac relaxation and reducing the need for intensive safety monitoring seen with current therapies. Preclinical data suggest that EDG-7500 can elicit a broad clinical response without significantly reducing LV ejection fraction, making it a promising candidate for fixed-dose regimens.

Edgewise Therapeutics continues to demonstrate its commitment to developing novel treatments for serious muscle diseases. Alongside EDG-7500, the company is also advancing Sevasemten, a skeletal myosin inhibitor, in late-stage clinical trials for Becker and Duchenne muscular dystrophies. The company’s mission remains focused on transforming the lives of patients and families affected by severe muscle conditions.