SCOUT-HCM: Mavacamten Outperforms Placebo in Adolescents With HCM, With Joseph Rossano, MD, MS

Mavacamten exhibited greater reduction of left ventricular outflow compared to placebo in adolescent patients with obstructive hypertrophic cardiomyopathy (HCM), according to data from the SCOUT-HCM trial.1,2

These data were presented at the American College of Cardiology (ACC) Scientific Sessions 2026 in New Orleans, Louisiana, by Joseph Rossano, MD, MS, co-director of the Cardiac Center and chief of the division of cardiology at the Children’s Hospital of Philadelphia, as well as the Jennifer Terker Endowed Chair in Pediatric Cardiology.

“Prior to this, what we used for children was really aimed at helping to alleviate their symptoms, and it wasn’t actually based on very strong evidence that it was helpful for those patients,” Rossano told HCPLive in an exclusive interview. “It’s really extrapolated from what we use for adult patients. To see such dramatic reductions in the gradients, as well as the improvements in the secondary endpoints, is really encouraging.”

SCOUT-HCM is an ongoing phase 3, double-blind, randomized, placebo-controlled trial consisting of active-treatment and long-term extension periods. Patients were eligible for inclusion if they were aged 12 to <18 years and had received a diagnosis of HCM, which was defined as a maximal left ventricular wall thickness of ≥15 mm (or ≥13 mm with a family history of HCM), had a left ventricular outflow tract pressure gradient during the Valsalva maneuver of ≥30 mmHg, or had a maximal left ventricular outflow tract gradient of ≥50 mmHg, among other criteria. Patients with HCM phenocopies, such as Noonan syndrome and Fabry disease, were excluded.2

After confirming eligibility via a 5-week screening period, Rossano and colleagues randomly assigned enrolled patients in a 1:1 ratio to receive mavacamten or placebo during the 28-week treatment period. Mavacamten was started at a once-daily dose of 5 mg in patients with body weight of ≥45 kg (99.2 lb) or 2.5 mg in patients with a body weight of 35 to <45 kg (77.2 to <99.2 lb). This dose could be adjusted down at weeks 5 and 9 or up at weeks 12 and 24 by 1 dose level, based on electrocardiographic assessment of the Valsalva left ventricular outflow tract gradient and LVEF.2

The study’s primary endpoint was the change in left ventricular outflow tract pressure gradient provoked by the Valsalva maneuver from baseline. Secondary endpoints included the change from baseline in resting and postexercise left ventricular outflow tract gradients, the maximal left ventricular wall thickness, and the ratio of early mitral inflow velocity to mitral annular early diastolic velocity.2

A total of 65 patients were screened for eligibility – of these, 44 were included and assigned to the mavacamten arm (n = 23) or the placebo arm (n = 21). All patients in the mavacamten arm had a dose adherence of ≥80%. Over the course of the study, mean Valsalva left ventricular outflow tract gradient decreased from 78.4 +/- 34.1 mmHg at baseline to 29 +/- 18.3 mmHg at week 28 in the mavacamten group (least-squares mean change, -48.5 mmHg; 95% CI, -63 to -34). The placebo arm exhibited a decrease from 80.8 +/- 47.4 mmHg to 72.7 +/- 40.1 mmHg (least-squares mean change, -0.5 mmHg; 95% CI, -18.7 to 17.6). This corresponded to a significant difference of -48 mmHg (95% CI, -67.7 to -28.3).2

Rossano and colleagues reported adverse events in 18 patients (78%) in the mavacamten group versus 17 (81%) in the placebo group. The former saw 2 patients with serious adverse events – 1 patient had 2 episodes of syncope, and the other had an inappropriate shock from an implantable cardioverter-defibrillator. Among the placebo recipients, 2 patients had serious adverse events – 1 had chest pain, and the other had depression with suicidal ideation.2

“Importantly, there were really no safety issues,” Rossano said. “We think the medication can be used safely in patients with pretty significant disease. Are there patients who may benefit more than others? Absolutely, that may be the case. I think we just need further study in larger populations over longer periods to try to sort that out.”

Editors’ Note: Rossano reports disclosures with Bristol Myers Squibb, AskBio, Astellas, Merck, and Bayer.

References

1. Rossano J, Canter E, Wolf C, et al. Mavacamten in Symptomatic Adolescent Patients With Obstructive Hypertrophic Cardiomyopathy: Results From the Phase 3 Scout-HCM Trial. Abstract presented at the American College of Cardiology Scientific Sessions 2026 in New Orleans, LA. March 28-30, 2026.

2. Rossano JW, Canter C, Wolf CM, et al. Mavacamten in adolescents with obstructive hypertrophic cardiomyopathy. NEJM. Published online March 29, 2026. doi:10.1056/nejmoa2601103