Treatment with mavacamten, compared with placebo, results in significantly greater reduction in left ventricular outflow tract (LVOT) obstruction over 28 weeks among adolescent patients with obstructive hypertrophic cardiomyopathy (HCM), as shown in the SCOUT-HCM trial.
“These results, from one of the few randomized controlled trials in cardiology of a targeted pharmacological therapy in adolescents, support the use of mavacamten as an efficacious treatment option for symptomatic obstructive HCM in adolescent patients,” said lead author Dr Joseph William Rossano, chief of cardiology at Children’s Hospital of Philadelphia, Philadelphia, US.
SCOUT-HCM is a phase III, double-blind, randomized, placebo-controlled trial involving 44 symptomatic adolescents (aged 12 to <18 years) with New York Heart Association class II or III obstructive HCM. They were randomly assigned in a 1:1 ratio to receive either mavacamten (n=23; mean age 14.7 years) or placebo (n=21; mean age 14.6 years). The change in LVOT pressure gradient provoked by the Valsalva maneuver from baseline to week 28 was the primary endpoint.
At baseline, the mean Valsalva LVOT gradient was similar between groups (78.4 vs 80.8 mm Hg, respectively). At week 28, the mavacamten group showed significantly greater least squares mean change in the Valsalva LVOT gradient than the placebo group (‒48.5 vs ‒0.5 mm Hg; difference, ‒48.9 mm Hg, 95 percent confidence interval, ‒67.7 to ‒28.3; p<0.001). [N Engl J Med 2026;doi:10.1056/NEJMoa2601103]
In terms of safety, the incidence of adverse events (AEs) did not significantly differ between the two groups, and serious AEs occurred in two patients in each arm. In the mavacamten group, one patient experienced two episodes of syncope, and another had an inappropriate shock delivered by an implantable cardioverter defibrillator. In the placebo group, chest pain developed in one patient and depression with suicidal ideation in another.
None of the patients demonstrated a <50-percent reduction in left ventricular ejection fraction. More importantly, no patient died during the trial.
“These results are very encouraging. Patients feel better, and their hearts look better,” Rossano said in a press statement.
“This medicine was specifically designed for HCM and treats the underlying pathophysiology. This is what we hope to do in healthcare—to get medicines that are targeted for the underlying problem,” he added.
Cardiac structure
The changes seen in left ventricular wall thickness and measures of diastolic function with mavacamten vs placebo were consistent with the improvement in the primary endpoint.
“We speculate that this may reflect a beneficial effect on cardiac structure, a finding consistent with those observed in previous trials of mavacamten,” according to Rossano and his team. [Circ Cardiovasc Imaging 2022;15:e014986; J Am Coll Cardiol 2021;78:2518-2532]
Furthermore, “our analysis indicated a possible association between mavacamten and reduced levels of NT-proBNP and high-sensitivity cardiac troponin I, two markers of disease severity that are associated with serious adverse outcomes, including progression of heart failure and death,” they added. [Eur Heart J 2013;34:2529-2537; Eur Heart J 2013;34:2529-2537; Heart 2021;107:1576-1583; Circ Cardiovasc Qual Outcomes 2024;17:e010243]
Adolescents with HCM may experience a cumulative burden of adverse outcomes throughout their life, potentially resulting in a poor long-term prognosis. [Circulation 2018;138:1387-1398]
Therefore, intervention prior to adulthood could improve clinical outcomes later in life, “given the relatively aggressive phenotype as compared with adult-onset HCM, but further data are needed,” according to Rossano and his team. [Heart Rhythm 2019;16:1462-1467; Eur Heart J 2019;40:3672-3681]
“Data from the ongoing active treatment and long-term extension periods (approximately 3 years in total) of the current trial may establish whether this reversal in hypercontractility is sustained over longer exposure,” Rossano and colleagues said.
“The long-term extension study for SCOUT-HCM is ongoing,” Rossano said.