News Report · Pharmacology

EXPLORER-HCM: Mavacamten Achieved 37% Versus 17% Primary Endpoint in Obstructive HCM

July 24, 2026

Primary endpoint (composite)

45 (37%) mavacamten vs 22 (17%) placebo (difference +19.4%, 95% CI 8.7 to 30.1; p=0.0005)

Post-exercise LVOT gradient

-36 mm Hg (95% CI -43.2 to -28.1; p<0.0001)

Peak VO2 change

+1.4 mL/kg per min (95% CI 0.6 to 2.1; p=0.0006)

NYHA class improvement

80 of 123 mavacamten vs 40 of 128 placebo; 34% more patients improved by ≥1 class (95% CI 22.2 to 45.4; p<0.0001)

Enrollment and arms

251 patients randomized: mavacamten n=123; placebo n=128; 30-week treatment

Clinical Perspective

Cardiologists and clinicians who treat adults with obstructive hypertrophic cardiomyopathy can view the EXPLORER-HCM data as evidence that mavacamten produced a 19.4% absolute difference in the trial's composite primary endpoint versus placebo and improved LVOT gradient, exercise capacity, symptoms, and health-status scores ^[1]. The source-confirmed data support that mavacamten produced measurable improvements in exercise capacity, LVOT obstruction, NYHA functional class, and patient-reported health status over 30 weeks in this population ^[1]. What are the longer-term efficacy and safety outcomes of mavacamten beyond 30 weeks and across broader clinical populations?

Editorial Team · Pharmacology

Mavacamten achieved the prespecified composite primary endpoint in 37% versus 17% with placebo in adults with obstructive hypertrophic cardiomyopathy in the EXPLORER-HCM trial ^[1]. The randomized, double-blind, placebo-controlled phase 3 study reported these results after 30 weeks of treatment in patients with an LVOT gradient of 50 mm Hg or greater and NYHA class II-III symptoms ^[1].

Clinical Context

Cardiac muscle hypercontractility and dynamic left ventricular outflow tract (LVOT) obstruction are cited as key pathophysiological abnormalities in hypertrophic cardiomyopathy in the trial background, and they are major determinants of symptoms in obstructive disease ^[1]. The trial report describes available pharmacological options for hypertrophic cardiomyopathy as inadequate or poorly tolerated and not disease-specific, and positions mavacamten as a first-in-class cardiac myosin inhibitor intended to target that hypercontractility ^[1]. The EXPLORER-HCM results therefore address disease-specific efficacy measures reported by the investigators ^[1].

Key Findings

The EXPLORER-HCM trial showed mavacamten achieved the composite primary endpoint in 45 (37%) of 123 patients versus 22 (17%) of 128 with placebo (difference +19.4%, 95% CI 8.7 to 30.1; p=0.0005) ^[1].
Mavacamten produced a greater reduction in post-exercise LVOT gradient: -36 mm Hg versus placebo (95% CI -43.2 to -28.1; p<0.0001) ^[1].
Peak oxygen consumption increased more with mavacamten: +1.4 mL/kg per min versus placebo (95% CI 0.6 to 2.1; p=0.0006) ^[1].
Health-status measures improved with mavacamten: KCCQ-CSS +9.1 (95% CI 5.5 to 12.7) and HCMSQ-SoB -1.8 (95% CI -2.4 to -1.2; p<0.0001) compared with placebo ^[1].
Functional class improved: 80 of 123 patients on mavacamten versus 40 of 128 on placebo improved by at least one NYHA class (34% more patients; 95% CI 22.2 to 45.4; p<0.0001) ^[1].
The trial registered on ClinicalTrials.gov as NCT03470545 and is described as the pivotal randomized, double-blind, placebo-controlled phase 3 EXPLORER-HCM trial ^[1].

Safety & Tolerability

Safety and tolerability were similar to placebo in the trial report ^[1].
Treatment-emergent adverse events were generally mild according to the publication ^[1].
One patient died by sudden death in the placebo group as reported in the trial publication ^[1].

Study Design

EXPLORER-HCM was a phase 3, randomized, double-blind, placebo-controlled trial conducted in 68 clinical cardiovascular centres in 13 countries ^[1]. Adults with hypertrophic cardiomyopathy, an LVOT gradient of 50 mm Hg or greater, and NYHA class II-III symptoms were randomized 1:1 to mavacamten (starting at 5 mg) or placebo for 30 weeks, with assessments every 2–4 weeks; the primary endpoint was a composite based on prespecified pVO2 and NYHA class thresholds ^[1]. Clinicians should consult current prescribing information for full dosing guidance. The trial enrolled 251 patients (mavacamten n=123; placebo n=128) and is registered as NCT03470545 ^[1].

FAQ

Q1 What did the EXPLORER-HCM trial show?

The EXPLORER-HCM trial demonstrated that mavacamten met the prespecified composite primary endpoint in 45 (37%) of 123 patients versus 22 (17%) of 128 on placebo, an absolute difference of +19.4% (95% CI 8.7 to 30.1; p=0.0005). Secondary outcomes included a -36 mm Hg greater reduction in post-exercise LVOT gradient, a +1.4 mL/kg per min greater increase in pVO2, and improvements in KCCQ-CSS and HCMSQ-SoB versus placebo.

Q2 Who was enrolled in EXPLORER-HCM?

The trial enrolled adults with hypertrophic cardiomyopathy who had an LVOT gradient of 50 mm Hg or greater and New York Heart Association (NYHA) class II-III symptoms. The study was conducted across 68 cardiovascular centres in 13 countries, and 251 patients were randomized 1:1 to mavacamten (n=123) or placebo (n=128) for 30 weeks (registered as NCT03470545).

Q3 What were the side effects reported in the trial?

The publication reports that safety and tolerability were similar to placebo and that treatment-emergent adverse events were generally mild. The trial report notes one patient death by sudden death in the placebo group; specific adverse-event frequencies and detailed safety monitoring data are reported in the full manuscript.

Q4 What does the EXPLORER-HCM trial mean for clinical practice?

The EXPLORER-HCM results provide source-confirmed evidence that mavacamten improved exercise capacity, reduced LVOT obstruction, improved NYHA functional class, and improved patient-reported health status over 30 weeks in adults with obstructive hypertrophic cardiomyopathy. Clinicians should consult the full trial publication and product-specific prescribing information for detailed eligibility, dosing, and safety data when considering applicability to patient care.

References

PubMed — Primary trial publication (PMID 32871100)

EXPLORER-HCM: Mavacamten Achieved 37% Versus 17% Primary Endpoint in Obstructive HCM

EXPLORER-HCM: Mavacamten Achieved 37% Versus 17% Primary Endpoint in Obstructive HCM

Clinical Perspective

Clinical Context

Key Findings

Safety & Tolerability

Study Design

FAQ

References

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