Mavacamten, a drug initially developed to treat hypertrophic cardiomyopathy, has shown signs of reducing heart stress in patients with heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) affects nearly half of all heart failure patients. It is characterized by the heart’s inability to appropriately fill with blood despite normal pumping strength.

Patients with left ventricular ejection fraction (LVEF) of 60% or greater make up 43% to 46% of those with HFpEF. These individuals often show a reduced response to standard heart failure treatments, making effective therapy options limited.

Mavacamten is a cardiac myosin inhibitor already approved for treating hypertrophic cardiomyopathy (HCM) and has demonstrated its ability to lower specific biomarkers in non-obstructive HCM cases. Researchers hypothesized that similar mechanisms could benefit HFpEF patients by improving heart muscle relaxation and reducing stress on the heart.

In a Brief Report titled “Cardiac Myosin Inhibition in Heart Failure With Normal and Supranormal Ejection Fraction: Primary Results of the EMBARK-HFpEF Trial,” published in JAMA Cardiology, the multi-centered team led by Northwestern University Feinberg School of Medicine detail their preliminary results.

The team reports that 26-week treatment with mavacamten was associated with statistically significant reductions in cardiac biomarkers that indicate heart stress and injury in patients with HFpEF and an LVEF of 60% or greater.

EMBARK-HFpEF is a Phase IIa, open-label, single-arm study conducted across 20 sites. It involved 30 patients with symptomatic HFpEF and an LVEF of 60% or greater. Patients were treated with mavacamten for 26 weeks, starting with a daily dose of 2.5 mg, with an option to increase to 5 mg based on their heart function assessments at week 14.

The study revealed that mavacamten treatment was associated with significant reductions in cardiac biomarkers that indicate heart stress. Levels of N-terminal pro-B-type natriuretic peptide decreased by an average of 26%.

High-sensitivity troponin T levels dropped by 13%, and high-sensitivity troponin I saw a 20% reduction. These changes suggest a decrease in cardiac wall stress and injury during treatment. Eight weeks after treatment ended, these biomarkers trended back toward baseline levels, indicating a potential direct effect of mavacamten.

Using the New York Heart Association classification, which measures the severity of heart failure symptoms, 41.7% of patients improved by at least one class by the end of the treatment period.

The safety profile of mavacamten was generally favorable. While three patients experienced a decrease in LVEF that required temporary discontinuation of the drug, all recovered their heart function, and the treatment was resumed without major complications. There were no reports of severe adverse events or deaths related to mavacamten during the study period.

The findings should be interpreted with caution. The research team emphasized that more extensive randomized controlled trials are needed to confirm the efficacy and safety of mavacamten in this patient population.

A new Phase II randomized clinical trial, the AURORA-HFpEF trial, is underway to further evaluate mavacamten’s impact on HFpEF with preserved ejection fraction. Researchers hope that these forthcoming studies will provide clearer evidence regarding the drug’s potential role in managing this challenging form of heart failure.