SCOUT-HCM: Mavacamten Can Benefit Teens With Obstructive HCM, Too

NEW ORLEANS, LA—Mavacamten (Camzyos; Bristol Myers Squibb) better reduces left ventricular outflow tract (LVOT) obstruction than placebo among adolescent patients with obstructive hypertrophic cardiomyopathy (HCM), according to data from the SCOUT-HCM phase III trial.

In 2022, the US Food and Drug Administration approved the cardiac myosin inhibitor for use in adults with NYHA class II or III obstructive HCM based on the EXPLORER-HCM trial. SCOUT-HCM focused its sights on younger individuals.

“HCM is the most common inherited cardiovascular disorder,” Joseph Rossano, MD (Children’s Hospital of Philadelphia, PA), lead investigator for SCOUT-HCM, pointed out in his presentation at the American College of Cardiology 2026 Scientific Session.

The prevalence of pediatric-onset HCM is in the ballpark of three to nine cases per 100,000 children, carrying a worse prognosis than adult-onset HCM, he said. “LVOT obstruction is common in HCM and can lead to severe symptoms, heart failure, or surgical myectomy.”

Yet, as Rossano noted, no FDA-approved therapies exist to address this disease in pediatric patients. “Targeted pharmacological therapy for pediatric patients is needed to effectively reduce LVOT obstruction and improve symptoms,” he said.

Biykem Bozkurt, MD, PhD (Baylor College of Medicine, Houston, TX), commenting on the SCOUT-HCM results at a press conference, highlighted some differences between the adult and pediatric HCM patients.

“When the expression of HCM starts being manifested in pediatrics, it usually is a severe disease that portends a worse prognosis,” she noted. LVOT gradients and LV wall thickness in these young patients exceeded what’s been seen in adult-focused trials, said Bozkurt, but despite this severity, the drug therapy had a positive impact on these endpoints without reducing ejection fraction.

Kenneth B. Margulies, MD (Penn Medicine, Philadelphia, PA), discussant for SCOUT-HCM in the late-breaking clinical trials session, told attendees that the “results will surely change clinical practice.”

While there have been several trials of cardiac myosin inhibitors in HCM, this one stands out for its adolescent participants. “Your presentation and your study remind us that there’s a whole other world of individuals who need their own studies in these broader areas, and that’s our pediatric populations,” said Margulies. “[It’s] a rare but compelling contribution that I hope will be the beginning of many more in this regard.”

SCOUT-HCM

For the trial, published online in the New England Journal of Medicine, investigators enrolled 44 symptomatic adolescents (ages 12 to < 18 years) with NYHA class II or III obstructive HCM, randomizing them in a double-blind fashion to receive mavacamten (2 or 5 mg daily based on body weight) or placebo. Thirty percent of the participants were female, the mean age was slightly less than 15 years, and almost 70% were white.

More than half were identified as having a pathogenic or likely pathogenic genetic mutation. Median NT-proBNP levels were 1,776 and 1,294 pg/mL, respectively, for the treatment and control groups, with elevations also seen for high-sensitivity troponin I (36.1 and 22.7 pg/mL) and troponin T (25.3 and 16.7 pg/mL). Maximal LV wall thickness was 28.3 mm in mavacamten-treated patients and 24.7 mm in those who received placebo.

“Background therapy was high,” said Rossano. Nearly 85% were on beta-blockers, 11.4% on calcium channel blockers, and 20.5% on disopyramide.

Mean Valsalva LVOT gradient at baseline was similar in the two groups. Change in LVOT gradient between baseline and week 28, the study’s primary endpoint, was greater in the mavacamten versus placebo group (P < 0.0001).

SCOUT-HCM: Mean Valsalva LVOT Gradient, mm Hg

Importantly, Rossano stressed, “Valsalva LVOT gradient in the mavacamten group was reduced to below the guideline criteria for obstruction.” Data also indicated improvements in resting and postexercise LVOT gradients, maximal LV wall thickness, and average E/e’. An exploratory analysis looking at biomarker changes with mavacamten found reductions in NT-proBNP as well as troponin I and T.

Safety measures did not differ between the study arms. Two patients in the mavacamten group had an adverse event: one with two episodes of syncope and another with an inappropriate shock delivered by an implantable cardioverter-defibrillator. In the placebo group, one patient experienced chest pain and another had depression with suicidal ideation. No deaths occurred, none of the patients had their LVEF drop below 50%, and none discontinued treatment due to an adverse event.

“These results, which are from one of the few prospective randomized trials of medical therapy for cardiovascular disease in childhood, support the use of mavacamten as an efficacious treatment option for symptomatic obstructive HCM in adolescent patients,” Rossano concluded, adding that a “long-term extension study for SCOUT-HCM is ongoing.”

Margulies highlighted the changes in mean maximal LV wall thickness between baseline and 26 weeks—decreasing by 2 mm in the mavacamten group and increasing by 1 mm in the placebo group—asking whether these changes occurred progressively during follow-up. “It tells us both that this is a very dynamic process and that there seems to be an impact on that,” he observed.

“I think some of these secondary and exploratory endpoints are among the most exciting things from this study and really give some hope [about] what these medications may do,” said Rossano, adding that 56-week follow-up should be available soon.

“One could imagine if those findings were sustained or even continue to improve over time, what a dramatic effect that could have for these young people, potentially over the course of their lifetime,” Rossano emphasized. “How could this change the natural history of the disease? If we could improve the hemodynamics, improve the relentless damage that these hearts are seeing over 10, 20, 30, 40 years, then we’d be in a much better place.”