Edgewise Therapeutics has shared encouraging interim updates from its ongoing CIRRUS-HCM Phase 2 trial evaluating EDG-7500, a novel oral therapy for hypertrophic cardiomyopathy (HCM).
The data reinforce EDG-7500’s potential as a differentiated treatment that improves cardiac relaxation without compromising systolic function, a key limitation of existing therapies.
Why EDG-7500 Matters in HCM?
Hypertrophic cardiomyopathy is driven by excessive cardiac contraction and impaired relaxation. Many current therapies risk reducing left ventricular ejection fraction (LVEF).
EDG-7500 is designed to:
- Slow early cardiac contraction velocity
- Improve diastolic relaxation
- Preserve systolic function
This combination directly targets two central goals in HCM management.
CIRRUS-HCM Trial Overview
CIRRUS-HCM is a multi-part, open-label Phase 2 study enrolling patients with:
- Obstructive HCM (oHCM)
- Nonobstructive HCM (nHCM)
The trial evaluates multiple fixed and optimized doses of EDG-7500.
Key Findings From Parts B and C
Earlier cohorts tested 25 mg, 50 mg, and 100 mg fixed doses.
Across these groups, EDG-7500 showed improvements in core HCM markers:
- NT-proBNP reductions, indicating improved cardiac stress
- KCCQ score improvements, suggesting better quality of life
- NYHA class improvements, reflecting functional gains
- LVOT gradient reductions in obstructive HCM patients
Importantly:
- No clinically meaningful LVEF reductions were observed
- No LVEF values dropped below 50%
- No atrial fibrillation events were reported
Part D: Dose Optimization and Safety Focus
Part D is designed to:
- Explore exposure–response relationships
- Optimize dosing using biomarkers
- Inform Phase 3 trial design
Participants receive doses ranging from 25 mg to 150 mg, with potential escalation to 200 mg.
As of the December 23, 2025 cutoff:
- Over 40 patients enrolled
- ~70% reached 100 mg or higher
- Dosing guided by LVOT-G (oHCM) and NT-proBNP (nHCM)
Strong Safety Signal Continues
Among the first 20 participants completing 12 weeks in Part D:
- EDG-7500 remained well tolerated
- No clinically significant LVEF declines
- No detected atrial fibrillation or flutter during monitored periods
Over 2,600 patient-days of cardiac monitoring showed no clinically meaningful arrhythmias. One AF event occurred off-monitoring and was deemed unrelated to treatment.
How EDG-7500 Stands Apart From CMIs?
Unlike cardiac myosin inhibitors (CMIs), EDG-7500:
- Does not impair systolic function
- Avoids intensive cardiac safety monitoring burdens
- May be suitable beyond specialty HCM centers
This profile could significantly expand patient access if approved.
What’s Next for Edgewise?
Edgewise plans to:
- Report full Part D efficacy and safety data in Q2 2026
- Finalize Phase 3 trial design
- Initiate Phase 3 studies by end of 2026
The Bigger Picture: Unmet Need in HCM
HCM affects 1 in 500 people globally. Patients often face breathlessness, fatigue, arrhythmias, and reduced quality of life. Despite recent advances, many patients still lack optimal treatment options.
EDG-7500 aims to change that equation.
Bottom Line
EDG-7500 continues to demonstrate:
- Consistent clinical improvements
- A differentiated safety profile
- Strong potential as a best-in-disease therapy
If these results hold in Phase 3, EDG-7500 could redefine how both obstructive and nonobstructive HCM are treated.
