Mavacamten Shows Benefit for Pediatric Patients in SCOUT-HCM Trial

A phase 3 randomized trial found mavacamten (Camzyos) significantly reduced left ventricular outflow tract (LVOT) obstruction in adolescents with symptomatic obstructive hypertrophic cardiomyopathy (oHCM).

The findings from the SCOUT-HCM trial were presented as a late-breaking clinical trial at the American College of Cardiology's Annual Scientific Session (ACC.26) and, according to Bristol Myers Squibb, represent the first prospective phase 3 evidence for a cardiac myosin inhibitor in a pediatric oHCM population.1

“Pediatric HCM is a rare cardiac disorder that is associated with severe, sometimes life-threatening, symptoms,” said principal investigator Joseph Rossano, MD, chief of the Division of Cardiology at Children’s Hospital of Philadelphia.2 “With no approved therapies for pediatric patients with oHCM and current recommendations for pharmacological therapy primarily extrapolated from evidence obtained from adult studies, the positive results of this trial represent a significant advance in the field of pediatric cardiology and the potential for a meaningful new therapy for adolescent patients if approved by the FDA.”

SCOUT-HCM Design and Population

SCOUT-HCM was a double-blind, randomized, placebo-controlled phase 3 trial enrolling adolescents aged 12 to less than 18 years with NYHA class II or III oHCM across 28 sites in 9 countries. Eligible patients had a Valsalva LVOT gradient of 30 mm Hg or greater, a maximal LVOT gradient of 50 mm Hg or greater, and a left ventricular ejection fraction (LVEF) of 60% or greater. Patients with HCM phenocopies such as Noonan syndrome or Fabry disease were excluded.1

Of 65 patients screened, 44 were randomized 1:1 to mavacamten or placebo for 28 weeks. The 23 patients in the mavacamten group and 21 in the placebo group had a mean age of approximately 14.7 years, 83% to 86% were on background beta-blocker therapy, and approximately half carried a pathogenic or likely pathogenic HCM mutation.1

Investigators pointed out the mean baseline Valsalva LVOT gradient was 78.4 mmHg in the mavacamten group and 80.8 mmHg in the placebo group. Additionally, mavacamten was initiated at 5 mg once daily for most patients, with dose adjustment permitted based on echocardiographic assessment.1

The primary endpoint was the change from baseline to week 28 in Valsalva LVOT gradient. Secondary outcomes of interest included the change from baseline to week 28 in resting and postexercise LVOT gradients, the maximal left ventricular wall thickness, and the ratio of early mitral inflow velocity to mitral annular early diastolic velocity (E/e′ ratio).1

48 mmHg Reduction in Valsalva LVOT Gradient

At week 28, the least-squares mean change in Valsalva LVOT gradient was -48.5 mmHg in the mavacamten group versus -0.5 mm Hg in the placebo group, a between-group difference of -48.0 mmHg (95% CI, -67.7 to -28.3; P <.001).1

Analysis of secondary outcomes of interest also favored mavacamten, including reductions in resting LVOT gradient (difference, -47.0 mm Hg; 95% CI, -62.7 to -31.4), postexercise LVOT gradient (difference, -41.7 mm Hg; 95% CI, -59.7 to -23.7), maximal LV wall thickness (difference, -1.8 mm; 95% CI, -3.4 to -0.2), and average E/e' ratio (difference, -3.4; 95% CI, -5.1 to -1.6). Investigators also called attention to exploratory analyses pointing to reductions in NT-proBNP and high-sensitivity cardiac troponin levels with mavacamten.1

Overall adverse event rates were similar between groups (78% mavacamten vs 81% placebo). Serious adverse events occurred in 2 patients per arm. A single patient in the mavacamten group had 2 episodes of syncope deemed related to study drug and another had an inappropriate ICD shock considered unrelated. No patient in either group died or experienced an LVEF below 50%, and no cases of atrial fibrillation or symptomatic heart failure were reported.1

Investigators highlighted several key limitations in their study to consider. These included the small sample size, restriction to ages 12 and older, a predominantly White study population, and the 28-week placebo-controlled follow-up period.1

“The SCOUT-HCM results underscore the potential for [mavacamten] to become the first CMI for adolescents, reinforcing our leadership in the CMI space and our role in reshaping the scientific understanding of oHCM and how the disease is diagnosed, evaluated and potentially treated,” said Cristian Massacesi, MD, executive vice president, chief medical officer, and head of development at Bristol Myers Squibb.2 “With these meaningful safety and efficacy data, we are excited about the potential to provide a paradigm-changing treatment for adolescents and their families.”

References:

1. Rossano JW, Canter C, Wolf CM, et al. Mavacamten in Adolescents with Obstructive Hypertrophic Cardiomyopathy. N Engl J Med. Published online March 29, 2026. Accessed March 30, 2026. doi:10.1056/NEJMoa2601103

2. Bristol Myers Squibb. Bristol Myers Squibb Presents Positive Results from Phase 3 SCOUT-HCM Trial Demonstrating Efficacy and Safety of Camzyos (mavacamten) in Adolescents with Symptomatic Obstructive Hypertrophic Cardiomyopathy (oHCM). Bms.com. Published March 29, 2026. Accessed March 30, 2026. https://news.bms.com/news/corporate-financial/2026/Bristol-Myers-Squibb-Presents-Positive-Results-from-Phase-3-SCOUT-HCM-Trial-Demonstrating-Efficacy-and-Safety-of-Camzyos-mavacamten-in-Adolescents-with-Symptomatic-Obstructive-Hypertrophic-Cardiomyopathy-oHCM/default.aspx