Mavacamten in Adolescents with Obstructive Hypertrophic Cardiomyopathy

Published March 29, 2026
N Engl J Med 2026;395:362-373
DOI: 10.1056/NEJMoa2601103
Abstract
Background
Approved pharmacologic therapies for pediatric hypertrophic cardiomyopathy are lacking, and surgical intervention may be indicated in patients with left ventricular outflow tract obstruction. The efficacy and safety of mavacamten, a cardiac myosin inhibitor that is available for adults, warrant evaluation in adolescents.
Methods
We conducted a phase 3, double-blind, randomized, placebo-controlled trial involving symptomatic adolescents (12 to <18 years of age) with New York Heart Association class II or III obstructive hypertrophic cardiomyopathy. The patients were randomly assigned in a 1:1 ratio to receive mavacamten or placebo. The primary end point was the change from baseline to week 28 in left ventricular outflow tract pressure gradient provoked by the Valsalva maneuver.
Results
A total of 44 patients underwent randomization; 23 patients (8 [35%] of whom were female) were assigned to mavacamten group, and 21 (5 [24%] of whom were female) were assigned to the placebo group. The mean (±SD) age of the patients was 14.7±1.7 years in the mavacamten group and 14.6±1.7 years in the placebo group, and the mean Valsalva left ventricular outflow tract gradient at baseline was similar in the two groups (78.4±34.1 mm Hg and 80.8±47.4 mm Hg, respectively). At week 28, the least-squares mean change in the Valsalva left ventricular outflow tract gradient was −48.5 mm Hg in the mavacamten group and −0.5 mm Hg in the placebo group (difference, −48.0 mm Hg; 95% confidence interval, −67.7 to −28.3; P<0.001). The incidence of adverse events was similar in the two groups. Two patients in each group had serious adverse events; in the mavacamten group, 1 patient had two episodes of syncope, and another had an inappropriate shock delivered by an implantable cardioverter–defibrillator; in the placebo group, 1 patient had chest pain, and another had depression with suicidal ideation. No patient had a reduction in the left ventricular ejection fraction to less than 50%. No deaths occurred during the trial.
Conclusions
Among adolescent patients with obstructive hypertrophic cardiomyopathy, the reduction in left ventricular outflow tract obstruction was significantly greater with mavacamten than with placebo over a 28-week period. (Funded by Bristol Myers Squibb; SCOUT-HCM ClinicalTrials.gov number, NCT06253221.)
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Notes
This article was published on March 29, 2026, at NEJM.org.
A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.
Supported by Bristol Myers Squibb.
Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
We thank the patients and families who made this trial possible, the trial teams from the participating sites, and Thomas Crighton, Ph.D., of Oxford PharmaGenesis for medical writing and editorial support (funded by Bristol Myers Squibb) on earlier versions of the manuscript.
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Published online: March 29, 2026
Published in issue: July 23, 2026
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Cited by
- Mavacamten in adolescent obstructive hypertrophic cardiomyopathy: SCOUTing a way forward, Heart Failure Reviews, 31, 1, (2026).https://doi.org/10.1007/s10741-026-10655-x
- Significance of the Echocardiographic Assessment of Longitudinal Left Ventricular Systolic Function in Children and Adolescents with Hypertrophic Cardiomyopathy, Journal of Clinical Medicine, 15, 13, (4911), (2026).https://doi.org/10.3390/jcm15134911
- Medical management of hypertrophic cardiomyopathy, Indian Heart Journal, (2026).https://doi.org/10.1016/j.ihj.2026.06.005
- What Are Heart Failure With Preserved Ejection Fraction Mimics and What Are They Mimicking? Insights Into Our Conceptualization of Heart Failure With Preserved Ejection Fraction as a Disease, Journal of Cardiac Failure, (2026).https://doi.org/10.1016/j.cardfail.2026.05.016
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* The trial included 44 symptomatic adolescents (12 to <18 years) with NYHA class II or III obstructive hypertrophic cardiomyopathy.
* Patients were randomized 1:1 to receive either mavacamten or placebo.
* The primary endpoint was the change in left ventricular outflow tract pressure gradient provoked by the Valsalva maneuver from baseline to week 28.
* Baseline mean Valsalva LVOT gradient was $78.4\pm34.1$ mm Hg for mavacamten and $80.8\pm47.4$ mm Hg for placebo.
* At week 28, the mean change in the Valsalva LVOT gradient was $-48.5$ mm Hg in the mavacamten group.
* At week 28, the mean change in the Valsalva LVOT gradient was $-0.5$ mm Hg in the placebo group.
* The difference in change between groups was $-48.0$ mm Hg ($95\%$ CI, $-67.7$ to $-28.3$; $P<0.001$).
* Adverse event incidence was similar across both groups.
* No patient experienced a reduction in left ventricular ejection fraction to less than 50%.
* No deaths occurred during the trial.

A phase 3, double-blind, randomized, placebo-controlled trial investigated the effect of mavacamten versus placebo in symptomatic adolescents (aged 12 to under 18) with New York Heart Association class II or III obstructive hypertrophic cardiomyopathy. Forty-four patients were randomized in a 1:1 ratio. The primary endpoint measured the change in left ventricular outflow tract pressure gradient provoked by the Valsalva maneuver from baseline to week 28. At baseline, the mean Valsalva gradient was similar across both groups (78.4±34.1 mm Hg for mavacamten and 80.8±47.4 mm Hg for placebo). By week 28, the mavacamten group experienced a mean reduction in the gradient of $-48.5$ mm Hg, compared to a change of only $-0.5$ mm Hg in the placebo group. This resulted in a statistically significant difference of $48.0$ mm Hg between the two groups ($P<0.001$). The incidence of adverse events was similar between the treatment arms; serious adverse events were observed in both groups, including syncope/inappropriate shock in the mavacamten group and chest pain/suicidal ideation in the placebo group.

The study demonstrates a substantial, statistically significant clinical benefit from mavacamten over placebo in reducing left ventricular outflow tract obstruction in adolescents with hypertrophic cardiomyopathy over a 28-week period. The magnitude of improvement ($48.0$ mm Hg difference) suggests that modulating cardiac myosin activity yields a superior hemodynamic outcome compared to placebo in this specific pediatric cohort, supporting the potential utility of myosin inhibitors beyond adult indications. A critical area for deeper analysis involves the safety profile, where adverse events were similar, though the types differed (arrhythmia risk versus psychological distress). This raises questions about tailoring long-term monitoring strategies for adolescents receiving novel therapies that affect myocardial mechanics. Furthermore, while efficacy is established, the implications for managing symptoms and surgical candidacy in this younger population require contextualization against evolving standards of care. What are the implications if the observed improvement is sustained, and what do the disparate safety signals suggest about the developmental sensitivity of pediatric cardiology patients to these interventions?

Mavacamten in Adolescents with Obstructive Hypertrophic Cardiomyopathy

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Executive Summary

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Mavacamten in Adolescents with Obstructive Hypertrophic Cardiomyopathy

Facts Only

Executive Summary

Full Take

Sentinel — Human