Joseph Rossano, MD, MS, is the 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.

Joseph Rossano, MD, MS

symptomatic obstructive hypertrophic cardiomyopathy (oHCM)

FDA Approval of Mavacamten for Adolescents Addresses Massive Unmet Need

Mavacamten was first approved in 2022 for adults with symptomatic oHCM to improve functional capacity and symptoms. Parent company Bristol Myers Squibb has reported that mavacamten has since been prescribed to >25,000 patients in the US. This approval establishes mavacamten as having the broadest indication of any approved cardiac myosin inhibitor (CMI) and addresses a population with significantly unmet need.

“I think this is paradigm-shifting as a proof of concept, that disease-specific therapies targeted to the underlying pathophysiology of the disease can be developed for use in children with cardiovascular disorders," Joseph Rossano, MD, MS, co-director of the cardiac center and chief of the division of cardiology at the Children’s Hospital of Philadelphia and lead author on the SCOUT-HCM trial, told 

 in an exclusive interview. “This is essentially the first time that we’ve had that, and I think it’s incredibly exciting for these patients, but maybe even more so for the field – it shows us what’s possible.”

The FDA’s approval was based on positive results from the SCOUT-HCM trial, a phase 3, double-blind, randomized, placebo-controlled trial comparing mavacamten to placebo in patients aged 12 to <18. Patients were eligible for inclusion if they had a diagnosis of HCM, left ventricular outflow tract (LVOT) obstruction, and recorded symptoms. Patients were excluded from the trial if they displayed left ventricular ejection fraction (LVEF) <50%, phenocopy diseases resulting in myocardial hypertrophy unrelated to sarcomere dysfunction, or planned HCM therapy escalation.

Following enrollment, patients were randomly assigned in a 1:1 ratio to either mavacamten or placebo. Mavacamten treatment began on day 1 and could be escalated from 1 mg to 15 mg, while placebo treatment was initiated from week 1 to week 28 before patients were switched to mavacamten during week 28. The trial continued for 200 weeks, with a primary outcome of change from baseline in Valsalva LVOT gradient at week 28. Secondary endpoints included change from baseline in resting LVOT gradient, change in post-exercise peak LVOT gradient, and change in maximal wall thickness, among others.

A total of 44 patients were enrolled in the trial, of whom 23 received mavacamten and 21 received placebo. The mean age (+/- standard deviation [SD]) of patients was 14.7 +/- 1.7 years in the mavacamten arm and 14.6 +/- 1.7 years in the placebo arm. Mean Valsalva LVOT gradient was similar in both arms at baseline (78.4 +/- 34.1 mmHg and 80.8 +/- 47.4 mmHg, respectively).

By week 28, the least-squares mean change in Valsalva LVOT gradient was -48.5 mmHg in the mavacamten arm and -0.5 mmHg in the placebo group (difference, -48 mmHg; 95% CI, -67.7 to -28.3; 

 <.001). Adverse events were similar between both groups – 2 patients in each arm had a serious adverse event. The mavacamten arm saw 1 patient experience 2 episodes of syncope, while another had an inappropriate shock from an implantable cardioverter-defibrillator; the placebo arm saw 1 patient with chest pain and another with suicidal ideation. No patients had a reduction in LVEF to <50%.

Ultimately, investigators concluded that LVOT obstruction saw significantly greater reductions with mavacamten compared to placebo. This led to the FDA’s approval in this population, expanding mavacamten’s indication and allowing a patient population with few treatment options a way of managing and improving their conditions.

“There’s huge unmet need in pediatric cardiology that certainly extends to other forms of cardiomyopathies, but also for all other sorts of pediatric cardiovascular disorders like congenital heart disease, and we really don’t have disease-specific therapies for these patients,” Rossano said. “I’m excited about the future – it’s possible for us to develop disease-specific therapies that can be successful. Mavacamten really just opens up the door for possibilities.”

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

Bristol Myers Squibb. U.S. Food and Drug Administration Approves Expanded Indication for Bristol Myers Squibb’s CAMZYOS (mavacamten) for the Treatment of Symptomatic Obstructive Hypertrophic Cardiomyopathy (oHCM) in Adults and Pediatric Patients. September 30, 2026. Accessed October 1, 2026. 

https://news.bms.com/news/corporate-financial/2026/U-S--Food-and-Drug-Administration-Approves-Expanded-Indication-for-Bristol-Myers-Squibbs-CAMZYOS-mavacamten-for-the-Treatment-of-Symptomatic-Obstructive-Hypertrophic-Cardiomyopathy-oHCM-in-Adults-and-Pediatric-Patients/default.aspx

Rossano JW, Canter C, Wolf CM, et al. Mavacamten in adolescents with obstructive hypertrophic cardiomyopathy. New England Journal of Medicine. 2026;395(4):362-373. 

Bristol Myers Squibb. A Study to Evaluate Mavacamten in Adolescents With Symptomatic Obstructive Hypertrophic Cardiomyopathy. ClinicalTrials.gov Identifier: NCT06253221. Updated December 19, 2025. Accessed October 1, 2026. 

https://clinicaltrials.gov/study/NCT06253221

Videos

Joseph Rossano, MD, MS, discusses the SCOUT-HCM trial, mavacamten’s expanded indication, and what it means for pediatric oHCM.

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.

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 

 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.

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.

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.

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).

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.

“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.

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.

Rossano JW, Canter C, Wolf CM, et al. Mavacamten in adolescents with obstructive hypertrophic cardiomyopathy. 

Rossano discusses the results of the phase 3 SCOUT-HCM trial, highlighting mavacamten’s comparative superiority in reducing left ventricular outflow.

Joseph Rossano, MD, MS

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