8-K: Edgewise Therapeutics Announces Positive Top-Line Results from Phase 2 CIRRUS-HCM Trial of EDG-7500

Edgewise Therapeutics reports positive top-line data from its Phase 2 CIRRUS-HCM trial, showcasing EDG-7500's potential in treating hypertrophic cardiomyopathy.

Summary

• Edgewise Therapeutics announced positive top-line data from the Phase 2 CIRRUS-HCM trial of EDG-7500 in patients with obstructive or nonobstructive hypertrophic cardiomyopathy (HCM).
• The CIRRUS-HCM trial is a multi-part, open-label trial of EDG-7500 in individuals with HCM.
• In obstructive HCM patients, EDG-7500 demonstrated dose-dependent reductions in left ventricular outflow tract gradient (LVOT-G) at rest and post Valsalva, with participants receiving 100 mg experiencing mean reductions from baseline of 71% and 58% in resting and provokable gradients, respectively.
• Treatment with 100 mg of EDG-7500 also showed a 62% mean reduction from baseline in NT-proBNP, a key biomarker of heart failure.
• Clinically meaningful improvements were observed on the Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS), with a substantial mean increase of 23 points observed at the 100 mg dose.
• 78% of participants improved by 1 NYHA Class, and 67% improved to NYHA Class I (asymptomatic).
• In nonobstructive HCM patients, EDG-7500 administration resulted in a dose-dependent reduction in NT-proBNP, with a 42% mean decrease from baseline at 100 mg.
• Substantial improvements in KCCQ-OSS and KCCQ-Clinical Summary Scores, with substantial mean increases of 17 points and 22 points, respectively, were observed at the 100 mg dose after only four weeks.
• The positive results were achieved without meaningful reductions in left ventricular ejection fraction (LVEF), and no LVEF values were below 50% at any measurement.
• The most frequently reported adverse events were dizziness, upper respiratory tract infection, and atrial fibrillation (AF), with most being mild to moderate in severity.
• The company anticipates reporting initial readout of 12-week data from the Part D Phase 2 CIRRUS-HCM trial in the second half of 2025 and initiating the Phase 3 CIRRUS-HCM trial in the first half of 2026.

Sentiment

Score: 8

Explanation: The document presents positive top-line data from a Phase 2 trial, indicating potential for EDG-7500 in treating HCM. While there are some adverse events reported, the overall tone is optimistic due to the clinically meaningful improvements observed.

Positives

• EDG-7500 showed significant reductions in LVOT-G in obstructive HCM patients.
• The drug led to a substantial decrease in NT-proBNP levels, indicating reduced heart failure biomarkers.
• Participants experienced clinically meaningful improvements in the KCCQ-OSS.
• A significant percentage of participants improved in NYHA functional class.
• EDG-7500 demonstrated a dose-dependent reduction in NT-proBNP in nonobstructive HCM patients.
• The treatment showed positive trends in echocardiographic parameters of diastolic function.
• The drug was generally well-tolerated, with most adverse events being mild to moderate.
• Clinical activity was observed without meaningful changes in LVEF, including no participant with a value below 50%.

Negatives

• The most frequently reported adverse events were dizziness, upper respiratory tract infection and atrial fibrillation (AF).
• Two participants experienced serious adverse events of AF requiring cardioversion.
• One participant discontinued treatment due to moderate dizziness.

Risks

• The company's products are early in development and have not been approved for commercial sale.
• Edgewise has a limited operating history and has not generated any revenue to date.
• The company needs substantial additional capital to finance its operations.
• Edgewise is substantially dependent on the success of sevasemten and EDG-7500.
• Clinical trials of product candidates may not demonstrate safety and efficacy.
• Product candidates may cause serious adverse events, toxicities, or other undesirable side effects.
• The outcome of preclinical testing and early clinical trials may not be predictive of the success of later clinical trials.
• Regulatory approval processes are lengthy, time-consuming, and inherently unpredictable.
• The company relies on third parties for the production of drugs.
• The company may not achieve adequate market acceptance for its products.
• The patient population for product candidates may be small.
• Regulatory authorities may not accept data from trials conducted in locations outside of their jurisdiction.
• The company may not be able to attract and retain highly skilled executive officers and employees.
• The company relies on third parties.

Future Outlook

Edgewise anticipates reporting initial data from Part D of the Phase 2 CIRRUS-HCM trial in the second half of 2025 and initiating the Phase 3 CIRRUS-HCM trial in the first half of 2026; they also plan to file an IND for a novel heart failure candidate in the first half of 2025 and report Phase 2 data in the first half of 2026.

Management Comments

• 'These early data with EDG-7500 are encouraging, with favorable changes across multiple domains, including robust improvements in KCCQ, which suggests a potential effect of EDG-7500 on LVOT obstruction, wall stress, and diastolic dysfunction,' said Ahmad Masri, M.D., M.S., Director of the Hypertrophic Cardiomyopathy Center at Oregon Health and Science University and CIRRUS-HCM Investigator.
• Anjali T. Owens, M.D., Medical Director, Center for Inherited Cardiac Disease, Associate Professor of Medicine, in the Perelman School of Medicine at the University of Pennsylvania and CIRRUS-HCM Investigator, stated that she is particularly encouraged by the strong improvements in diastolic function, as well as the overall symptom relief with little to no effect on systolic function.
• Kevin Koch, Ph.D., President and Chief Executive Officer, Edgewise Therapeutics, stated that they are optimizing their dosing strategy in Part D of CIRRUS-HCM in participants with obstructive and nonobstructive HCM, which will inform their plans for Phase 3.

Industry Context

The announcement positions Edgewise Therapeutics as a key player in the development of novel therapeutics for hypertrophic cardiomyopathy, a significant area of unmet medical need. The positive results from the Phase 2 trial could potentially differentiate EDG-7500 from existing treatments by offering clinically meaningful improvements without causing systolic dysfunction.

Comparison to Industry Standards

• The rates of atrial fibrillation (AF) observed in Parts B and C of the CIRRUS-HCM trial were in the range of those reported in other HCM Phase 2 clinical trials of cardiac myosin inhibitors.
• This suggests that the safety profile of EDG-7500 is comparable to other drugs in the same class.

Stakeholder Impact

• Shareholders: Positive trial results could lead to increased investor confidence.
• Patients: EDG-7500 offers a potential new treatment option for HCM.
• Employees: Successful development of EDG-7500 could lead to company growth and job security.
• Clinicians: The drug may provide a new tool for managing HCM patients.

Next Steps

• Report initial readout of 12-week data from the Part D Phase 2 CIRRUS-HCM trial in the second half of 2025.
• Initiate the Phase 3 CIRRUS-HCM trial in the first half of 2026.
• File an investigational new drug (IND) application for a novel candidate for the treatment of heart failure in the first half of 2025.
• Report data from the Phase 2 clinical trial of such candidate in the first half of 2026.
• Select a proprietary cardiometabolic product candidate based on preclinical proof-of-concept data in the second half of 2025.

Key Dates

Keywords

EDG-7500, hypertrophic cardiomyopathy, HCM, CIRRUS-HCM, clinical trial, LVOT-G, NT-proBNP, KCCQ-OSS, LVEF, cardiac sarcomere modulator, diastolic dysfunction, Edgewise Therapeutics