Mavacamten May Improve LV Hypertrophy in Obstructive Hypertrophic Cardiomyopathy

This article is part of Cardiology Advisor‘s coverage of AHA Scientific Sessions 2020.

Mavacamten was found to improve left ventricular (LV) hypertrophy in patients with obstructive hypertrophic cardiomyopathy (oHCM), according to study results presented at the American Heart Association (AHA) Scientific Sessions 2020, held virtually from November 13 to 17, 2020.¹

Mavacamten is a novel drug that inhibits cardiac myosin. This was an additional analysis of data from the Clinical Study to Evaluate Mavacamten (MYK-461) in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy trial (EXPLORER-HCM; ClinicalTrials.gov Identifier: NCT03470545). In this multicenter, double-blind, placebo-controlled, phase 3 study, symptomatic patients (N=244; mean age, 58.5 years; 40.6% women) with oHCM (ie, LV ejection fraction ≥55% and resting and/or provoked LV outflow tract gradient ≥50 mm Hg) were randomly assigned 1:1 to receive mavacamten (n=123) or placebo (n=128) for 30 weeks. Echocardiograms were performed every 2 to 4 weeks.

Treatment with mavacamten vs placebo led to significant reductions in left atrial volume index (-7.5 mL/m²; P <.0001), lateral E/e′ (-3.8; P <.0001), septal E/e′ (-3.4; P <.0001), and LV mass index (-15.5 g/m²; P <.0001).

In addition, a greater percentage of participants treated with mavacamten vs placebo achieved resolution of mitral valve systolic anterior motion (80.9% vs 34.0%, respectively; difference, 46.8%; P <.0001) and mitral regurgitation (9.0% vs 0.0%, respectively; difference, 9.0%; P =.0006).

“These findings suggest that [mavacamten] has beneficial effects on several adverse pathophysiologic processes that are hallmarks of oHCM,” noted the study authors.

“Improvement in the key echocardiographic features of hypertrophic cardiomyopathy supports the hypothesis that mavacamten can be used as a disease-specific therapy, which would be a significant advance in therapy for this population,” remarked lead study author, Sheila M. Hegde, MD, MPH, a cardiovascular medicine specialist at Brigham and Women’s Hospital and an instructor in medicine at Harvard Medical School in Boston, Massachusetts. “A long-term extension trial is ongoing and will provide additional insight on the long term-impact on cardiac structure and function.”²

Disclosures: The study was funded by MyoKardia. Some of the study authors reported affiliations with medical device and pharmaceutical companies. Please see the original reference for a full list of disclosures.

References

1. Hegde SM, Abraham TP, Jacoby D, et al. Mavacamten favorably impacts key pathophysiologic processes in obstructive hypertrophic cardiomyopathy: Results from the EXPLORER-HCM study. Presented at: AHA Scientific Sessions 2020; November 13-17, 2020. Presentation P1732.
2. New medication may treat underlying causes of hypertrophic cardiomyopathy [press release]. Dallas, Texas: American Heart Association; November 9, 2020.

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