Mavacamten Monotherapy Improves Cardiac Function in oHCM, With Ozlem Bilen, MD

Mavacamten monotherapy has proven its efficacy in improving cardiac function and symptoms in patients with obstructive hypertrophic cardiomyopathy (HCM), according to data from the COLLIGO-HCM trial.1

Mavacamten has long been known to improve cardiac function and symptoms in patients with HCM; several clinical studies have indicated its efficacy and favorable safety profile. However, little literature exists regarding monotherapy in real-world studies.1

The editorial team at HCPLive met with Ozlem Bilen, MD, associate professor of medicine in the cardiology division and chief of cardiology at Emory University Hospital, to discuss the implications of these data, highlighting the potential of mavacamten monotherapy in patients with HCM.

“When we looked into the improvements in NYHA class, about 60% of patients in mavacamten monotherapy and 61% of patients in background medical therapy had improved their NYHA class by ≥1 class,” Bilen told HCPLive. “And when we looked into the changes in LVOT gradients, we saw significant improvement in both groups as well. About 94% in monotherapy and 87% in the background therapy group have reached resting LVOT gradients of <30, which is the threshold used to define obstructive HCM.”

COLLIGO-HCM is an ongoing retrospective, observational, multicenter, international study, the study period of which ran from April 2022 to February 2025. Investigators collected data from 7 participating sites in 5 countries across 4 continents. To be included, patients were required to have ≥1 encounter with an HCM diagnosis during or after 2018 and be aged ≥18 years at the index date. Patients were excluded if they had an HCM phenocopy observed after the first HCM-associated encounter in the medical record.2

Investigators assessed longitudinal measurements of NYHA class, resting and Valsalva LVOT gradients, and LVEF throughout the trial. Safety outcomes included the proportion of patients who interrupted or permanently discontinued treatment due to an LVEF <50%, a label-mandated trigger for interruption of mavacamten treatment in routine clinical practice to avoid signs and symptoms of systolic dysfunction. In these instances, investigators took echocardiogram measurements at subsequent visits after interruption to confirm LVEF recovery to ≥50%.1

A total of 278 patients received mavacamten during the study period; of these, 20 received mavacamten monotherapy at baseline and 68 received mavacamten monotherapy after discontinuing background therapy. Additionally, 190 patients received mavacamten with down-titrated background therapy or background therapy without dose modification. The mean follow-up length was 35 weeks for the overall cohort, 41.4 weeks for the mavacamten monotherapy subgroup, and 32 weeks for the mavacamten with background therapy subgroup.1

By month 9, roughly 60% of patients exhibited a NYHA improvement of ≥1 class from baseline (45 of 75 patients; P <.0001) in the mavacamten monotherapy subgroup and 61% (89 of 146 patients; P <.0001) in the mavacamten with background therapy subgroup. No patients in the mavacamten subgroup and 1 patient in the background therapy subgroup exhibited worsened NYHA by ≥1 class at 9 months from baseline. Significant improvements in resting LVOT gradients were also observed in both subgroups at every measured timepoint; mean change from baseline to month 9 was -35.5 mmHg in the mavacamten monotherapy subgroup and -30.3 mmHg in the mavacamten background therapy subgroup (P <.0001).1

Mean LVEF remained ≥62% in the monotherapy subgroup and 61.4% in the background therapy subgroup through month 9. The mean change in LVEF was -3.2% in the monotherapy group and -5% in the background therapy group. Roughly 4% (11 of 278) of patients in the overall cohort interrupted therapy due to an LVEF <50%; 5 of these patients were in the monotherapy group and 6 in the background therapy group. Of these 11 patients, 10 had their LVEF recover after treatment interruption.1

Mavacamten monotherapy was ultimately associated with improvements in cardiac function and symptoms, and positive benefits to the risk profile over the 9-month follow-up period. Investigators noted consistency with improvements observed in patients treated with mavacamten and background therapy.1

“I think the main takeaway from this cohort and other clinical trial evidence is that mavacamten monotherapy is efficacious and quite safe, overall,” Bilen said. “And it is also safe to discontinue background medical therapy. I think in the long run, we will probably see a guideline update.”

Editor's Note: Bilen reports disclosures with Bristol-Myers Squibb and Cytokinetics.

References

1. Bilen O, Adler AS, Bastiaenen R, et al. Mavacamten monotherapy in real-world patients with obstructive hypertrophic cardiomyopathy: Evidence from Colligo-HCM. Circulation: Genomic and Precision Medicine. Published online November 10, 2025. doi:10.1161/circgen.125.005502

2. Bristol-Myers Squibb. COLLIGO-HCM: A Multinational Observational Study of the Real-World Effectiveness of Mavacamten Among Patients With Symptomatic Obstructive Hypertrophic Cardiomyopathy (oHCM) (COLLIGO-HCM). ClinicalTrials.gov Identifier: NCT06372457. Updated April 18, 2024. Accessed December 3, 2025. https://clinicaltrials.gov/study/NCT06372457