Mavacamten Safety and Real-World Data Emerging at ACC.26, With Matthew Martinez, MD

Real-world evidence continues to refine the clinical profile of mavacamten in obstructive hypertrophic cardiomyopathy (HCM), with new data from both the MARVEL-HCM cohort and a large US Risk Evaluation and Mitigation Strategy (REMS) registry analysis reinforcing its effectiveness and safety in routine practice.1,2

In an interview with HCPLive, Matthew Martinez, MD, associate professor of medicine, director of sports cardiology, and director of the Hypertrophic Cardiomyopathy program at Morristown Medical Center/Atlantic Health System, discussed the emerging data from the MARVEL-HCM trial, presented at the American College of Cardiology (ACC) Scientific Sessions 2026 in New Orleans, Louisiana.

“Most often, patients will ask, ‘How long have you been using this drug?’ So, the value of long-term safety data continues to be helpful,” Martinez told HCPLive. “When I’m educating patients about options, I don’t determine what therapy we’re going to use. I give them the option of what’s best for them, and then we can decide together which therapeutic option is the next best step. Ongoing, long-term data continues to be helpful in that discussion.”

In MARVEL-HCM, a multicenter study of 239 patients, women presented at an older age than men (68.5 vs 59.3 years) and with more advanced disease, including higher rates of New York Heart Association (NYHA) class III symptoms and more severe diastolic dysfunction. Over 48 weeks of treatment, patients experienced significant reductions in resting and Valsalva left ventricular outflow tract (LVOT) gradients, improved functional status, and decreased severity of mitral regurgitation. Left ventricular mass index declined in both groups, supporting a role for reverse remodeling, while left ventricular ejection fraction (LVEF) remained stable, and no new safety signals were observed.1

These findings are complemented by data from a large REMS-based analysis including more than 6000 patients treated with mavacamten in the United States. In this real-world cohort, 60% of patients were women and nearly two-thirds were older than 60 years, reflecting a population similar to that seen in clinical practice. Over a follow-up period of up to 22 months, reductions in LVOT obstruction were observed, with 70.3% of patients achieving a post-Valsalva gradient <30 mm Hg at 6 months.2

Among more than 5,500 patients in the REMS study with monitoring data, 4.6% experienced a reduction in LVEF to <50%, and only 1.3% required hospitalization for heart failure. At the level of individual assessments, these events were infrequent, occurring in <1% of evaluations. Most patients remained on low-dose therapy, with approximately three-quarters maintained on 5 or 10 mg daily.2

Taken together, these datasets highlight several clinically relevant themes. First, mavacamten demonstrates consistent effectiveness across diverse patient populations, including those with more advanced disease at baseline. Second, the drug appears to exert favorable effects on cardiac structure and hemodynamics beyond symptom relief. Third, real-world safety outcomes - particularly the low incidence of systolic dysfunction and heart failure - support the feasibility of REMS-guided monitoring in routine care.1,2

The MARVEL-HCM findings also underscore persistent sex-based disparities in disease recognition and severity at treatment initiation. Earlier diagnosis and referral, particularly among women, may further enhance the clinical benefits observed with mavacamten in obstructive HCM.2

“I think the real-world data is going to be critical,” Martinez said. “You’re already seeing the ability to be a little more granular with some of the real-world data, such as MARVEL and COLLIGO, because it allows us to ask other questions that may not have been specifically addressed during the clinical trials that led to mavacamten’s approval. All of these real-world studies allow us just a glimpse into what’s happening outside of large academic centers.”

Editors’ Note: Martinez reports disclosures with Bristol Myers Squibb, Cytokinetics, Major League Soccer, and the NHL Combine.

References

1. 1: Martinez M, Wheeler M, Mehra V, et al. Real-World Evidence from the MARVEL-HCM Multicenter Study of Mavacamten – A Sex-Based Analysis of Baseline Characteristics and Cardiac Structural and Functional Changes. Abstract presented at the American College of Cardiology Scientific Sessions 2026, New Orleans, LA. March 28-30, 2026.

2. 2: Desai MY, Seto D, Cheung M, et al. Mavacamten: Real-world experience from 22 months of the risk evaluation and mitigation strategy (REMS) program. Circulation: Heart Failure. 2024;18(1). doi:10.1161/circheartfailure.124.012441