ACC 2022: Update on Mavacamten for Obstructive Hypertrophic Cardiomyopathy

By Debra L. Beck, MSc  |  April 29, 2022  |  Cardiovascular Disease, Emerging Medicine

UPDATE APRIL 28, 2022: U.S. Food and Drug Administration approves mavacamten for the treatment of adults with symptomatic NYHA Class II-III obstructive hypertrophic cardiomyopathy (HCM) to improve functional capacity and symptoms

Mavacamten had a big week at the American College of Cardiology 2022 Scientific Sessions, with two positive Late-Breaking Clinical Trial sessions.  Mavacamten is an investigational, ​first-in-class, cardiac-specific myosin inhibitor that reduces the number of available actin-myosin cross-bridges and thus decreases excessive myocardial contractility.

VALOR-HCM: Mavacamten Reduces Need for Septal Reduction in HCM

In the new phase 3 VALOR-HCM trial, presented during the first Late-Breaking Clinical Trial session of the meeting, Milind Y. Desai, MD, MBA (Cleveland Clinic, Cleveland, OH), presented data demonstrating that the addition of mavacamten significantly reduced the need for septal reduction therapy (surgical myectomy or alcohol septal ablation) in patients with severely symptomatic obstructive hypertrophic cardiomyopathy (HCM) who met criteria for septal reduction therapy per the 2011 ACC/AHA Guidelines at baseline. 

The trial enrolled symptomatic patients with obstructive HCM, randomly assigned them to mavacamten (titrated using echocardiography) or placebo, and followed them for 16 weeks. Study participants were on maximally tolerated background regimens when they entered the trial and remained on them through the duration of the study.

At the end of the 16-week study period, only 17.9% of patients on mavacamten were still eligible for septal reduction therapy, compared with 76.8% of those assigned to placebo (p<0.0001). Significant improvements were also seen in heart failure symptoms, quality of life, post-exercise left ventricular outflow tract obstruction (LVOT), and key markers of heart damage (NT-proBNP and troponin I). 

The benefit seen in a clinically-relevant endpoint that matters to patients (the need for an invasive therapy and symptoms/quality of life), validated by objective measures (post-exercise left ventricular outflow tract obstruction and markers of heart damage), is promising, said Lynne Warner Stevenson, MD (Vanderbilt University Medical Center, Nashville, TN).

While additional data is needed to test the durability of the improvement over a longer period of time, achieving this clear clinical benefit in only 16 weeks is also noteworthy, she added.

Mavacamten’s Benefits Appear Stable Over the Longer-term 

In the EXPLORER-HCM trial, mavacamten was shown to markedly improve health status in patients with symptomatic obstructive HCM. Treated patients had significantly reduced LVOT gradients and improved symptoms, functional capacity, and health status over 30 weeks versus placebo. No safety signals were detected.

The MAVA-LTE (long-term extension) trial is an ongoing, dose-blinded, 5-year study of mavacamten. At ACC 2022, Florian Rader, MD (Cedars-Sinai Medical Center, Los Angeles, CA), shared longer-term data on 231 patients (mean age, 60 years; 39% female) originally enrolled in EXPLORER-HCM and now continuing to be followed in MAVA-LTE. The median time on study drug was 62.3 weeks. 

Significant improvements were seen at week 48 in resting and Valsalva LVOT (-35.6 mm Hg and -45.3 mm Hg, respectively), and these changes were sustained at 84 weeks (-32.8 mm Hg and -46.4 mm Hg, respectively). Similar benefits were seen in terms of reductions in NT-proBNP and improvements in NYHA class. At baseline, only 6% of patients were in NYHA Class I, but that percentage rose to 55% by week 48.

Mavacamten is currently under review by the U.S. FDA, with an approval decision expected by April 28, 2022. If approved (which is expected), mavacamten will fill an unmet need in the obstructive HCM market, which is dominated at present by non-specific therapies with limited effectiveness. 


Explore CurrentMD Cardiology

Share this article
Subscribe to Blog