Mavacamten Could Treat Underlying Causes of Hypertrophic Cardiomyopathy

Sheila Hegde, MD

Results of an analysis of the EXPLORER-HCM trial is adding further credence to the notion that mavacamten, an investigational therapy from MyoKardia, could improve heart function in patients with obstructive hypertrophic cardiomyopathy (HCM).

After primary results of EXPLORER-HCM demonstrated the efficacy of mavacamten in adults with symptomatic obstructive HCM, the latest analysis details possible reductions in the size of the left atrium, decreases in elevated filling pressures, and restoration of normal mitral valve motion with use of mavacamten from the trial.

“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,” said lead investigator Sheila M. Hegde, MD, MPH, a cardiovascular medicine specialist at Brigham and Women’s Hospital, in a statement from the American Heart Association (AHA).

Just a few months after the ESC 2020 presentation, mavacamten once again captured the attention of cardiologists at AHA’s Scientific Sessions 2020. Designed as an international, double-blind, placebo-controlled, phase 3 trial, the EXPLORER-HCM trial provided evidence that mavacamten led to significant improvements in reducing obstruction, improving exercise capacity, and symptoms of obstructive HCM.

In the current study, investigators used the echocardiographic data to examine the effect of mavacamten on focused measures of cardiac structure and function. Of note, echocardiograms were performed every 2-4 weeks over the 30-week study period.

For inclusion in the phase 3 trial, obstructive HCM patients were required to have a left ventricular ejection fraction of 55% or greater and a resting and/or provoked left ventricular outflow tract gradient of 50 mmHg or greater. Patients meeting these criteria were then assigned in a 1:1 ratio to either mavacamten or placebo for 30 weeks. In total, 251 patients were included. Of these, 244 patients completed the study and were included in the current analysis—the mean age for this patient population was 58.5 years and 40.6% were female.

Upon analysis, investigators found 30-week treatment with mavacamten was associated with significant reductions in left atrium volume index (-7.5 ml/m2; P <.0001), lateral E/e’ (-3.8; P <.0001), septal E/e’ (-3.4; P <.0001), and left ventricular mass index (-15.5 g/m2; P <.0001). Additionally, results suggested significantly more patients treated with mavacamten achieved resolution of mitral valve systolic anterior motion (80.9% vs 34.0%, difference of 46.8%; P <.0001) and mitral regurgitation (6.0% vs 0.0%; difference of 9.0%; P=.0006) compared to placebo therapy.

“These findings reinforced and extended data from prior open label trials. Additional changes in measures of cardiac structure and function were also observed including reduction in the size of the left atrium. Together, these results reflect this medication’s impact on the underlying pathophysiology of hypertrophic cardiomyopathy,” Hegde added. “A long-term extension trial is ongoing and will provide additional insight on the long term-impact on cardiac structure and function.”

This study, “Mavacamten Favorably Impacts Key Pathophysiologic Processes in Obstructive Hypertrophic Cardiomyopathy: Results From the EXPLORER-HCM Study,” was presented at AHA Scientific Sessions 2020.