Edgewise EDG-7500 Posts Positive Phase 2 CIRRUS-HCM Data in Obstructive HCM

Key Takeaways

• Fifty-three patients (20 oHCM, 33 nHCM) completed the open-label 12-week Part D cohort at doses of 25 mg to 150 mg.
• In oHCM, 90% showed hemodynamic improvement and 74% achieved NT-proBNP normalization (<150 pg/mL) or a ≥50% reduction; mean KCCQ-OSS rose 24 points.
• In nHCM, mean NT-proBNP fell about 65%, with 88% meeting normalization or ≥50% reduction; mean KCCQ-OSS rose 13 points.
• No LVEF reductions below 50% were reported; Edgewise targets Phase 3 start in Q4 2026 (NCT06347159).

What is EDG-7500 and how does CIRRUS-HCM work?

EDG-7500 is an oral, selective cardiac sarcomere modulator designed to slow early contraction velocity and improve impaired relaxation in symptomatic hypertrophic cardiomyopathy without compromising systolic function. CIRRUS-HCM is a multi-part, open-label trial of EDG-7500 in oHCM and nHCM at more than 20 U.S. sites, registered as NCT06347159.

Part D is a 12-week dose-exploration cohort meant to inform Phase 3. In oHCM, dosing was guided by left ventricular outflow tract gradient. In nHCM, dosing was guided by NT-proBNP. Both groups used 25 mg to 150 mg dose ranges.

What did Edgewise Therapeutics show in obstructive HCM?

According to the June 16, 2026 PR Newswire release, oHCM patients had significant LVOT gradient reductions at rest and post-Valsalva. Ninety percent demonstrated improvement in hemodynamic measures.

• 74% achieved NT-proBNP <150 pg/mL or a ≥50% reduction from baseline
• 24-point mean increase on KCCQ Overall Summary Score
• 70% improved by at least one NYHA functional class
• ~20% mean increase in e' lateral; E/e' improved by a mean of 5.3 points in a high-frame-rate sub-study

How did nonobstructive HCM patients respond?

nHCM results also centered on diastolic and symptomatic change. Edgewise reported an approximately 65% mean NT-proBNP reduction, with 88% of patients achieving normalization or a ≥50% drop. Mean KCCQ-OSS rose 13 points, and 64% improved by at least one NYHA class.

Diastolic markers moved in the same direction: e' lateral rose 37% on average, and the high-frame-rate sub-study showed a 6.1-point mean E/e' improvement. Those figures matter because nonobstructive HCM still has fewer approved pharmacologic options than obstructive disease.

What does the safety profile show so far?

EDG-7500 was generally well tolerated in the 53 Part D completers, with no new safety signals identified in the company release. Nearly all adverse events were mild to moderate. There were no meaningful LVEF changes and no LVEF reductions below 50%. Two patients (3.8%) had new-onset atrial fibrillation; investigators judged both events unrelated to study drug.

Edgewise also stated that across more than 700 echocardiograms in healthy adults and HCM patients, it observed no relationship between multiple systolic-function measures and EDG-7500 concentration. That claim is company-reported and still needs blinded Phase 3 confirmation.

Why does systolic preservation matter versus myosin inhibitors?

Cardiac myosin inhibitors have reshaped obstructive HCM care but carry systolic-function monitoring requirements. Edgewise positions EDG-7500 as a sarcomere modulator aimed at diastolic dysfunction without the same LVEF liability. CIRRUS-HCM Part D is open-label and modest in size, so cross-trial comparisons to placebo-controlled myosin-inhibitor Phase 3 programs are hypothesis-generating only.

For competitive intelligence teams, the near-term watch item is whether Phase 3 preserves the NT-proBNP, KCCQ, and NYHA signals without LVEF drops below 50% in a controlled setting.

What remains unproven after CIRRUS-HCM Part D

Part D does not establish regulatory approval, labeled dosing, or superiority versus approved HCM therapies. Open-label design can inflate patient-reported outcomes. Phase 3 has not started; Edgewise only targeted initiation for Q4 2026. Claims about market share, pricing, or definitive differentiation from the cardiac myosin inhibitor class are not supported by these top-line data and are omitted here.

Related NovaPharma coverage

• Tenaya TN-201 MyPEAK-1 interim HCM data
• Cytokinetics aficamten Phase 3 non-obstructive HCM timing
• Eli Lilly and Verve early heart drug data

Frequently Asked Questions

Primary Sources

1. PR Newswire — Edgewise CIRRUS-HCM Part D top-line release
2. ClinicalTrials.gov NCT06347159 — CIRRUS-HCM
3. SEC 8-K filing — Edgewise Therapeutics EDG-7500 update