Mavacamten reduced the mean Valsalva left ventricular outflow tract gradient by 49 mmHg compared to a 12 mmHg reduction with placebo at 30 weeks in patients with obstructive hypertrophic cardiomyopathy.
RCT (n=251)
Double-blind
Randomized
Does mavacamten improve functional capacity and symptoms in adults with symptomatic NYHA class II-III obstructive hypertrophic cardiomyopathy?
Mavacamten is a first-in-class cardiac myosin inhibitor approved for symptomatic obstructive hypertrophic cardiomyopathy, requiring strict monitoring of left ventricular ejection fraction due to the risk of heart failure.
Absolute Event Rate: -49% vs -12%
Hypertrophic cardiomyopathy (HCM) is a primary myocardial disorder characterized by left ventricular hypertrophy, hyperdynamic contraction, and impaired relaxation of the heart. These functional derangements arise directly from altered sarcomeric function due to either mutations in genes encoding sarcomere proteins, or other defects such as abnormal energetics. Current treatment options do not directly address this causal biology but focus on surgical and extra-sarcomeric (sarcolemmal) pharmacological symptomatic relief. Mavacamten (formerly known as MYK-461), is a small molecule designed to regulate cardiac function at the sarcomere level by selectively but reversibly inhibiting the enzymatic activity of myosin, the fundamental motor of the sarcomere. This review summarizes the mechanism and translational progress of mavacamten from proteins to patients, describing how the mechanism of action and pharmacological characteristics, involving both systolic and diastolic effects, can directly target pathophysiological derangements within the cardiac sarcomere to improve cardiac structure and function in HCM. Mavacamten was approved by the Food and Drug Administration in April 2022 for the treatment of obstructive HCM and now goes by the commercial name of Camzyos. Full information about the risks, limitations, and side effects can be found at www. accessdata. fda. gov/drugsatfdadocs/label/2022/214998s000lbl. pdf.
Nag et al. (2023) conducted an RCT in Obstructive hypertrophic cardiomyopathy (HCM) (n=251). Mavacamten vs. Placebo was evaluated on Mean change from baseline in Valsalva LVOT gradient at Week 30 (mmHg). Mavacamten reduced the mean Valsalva left ventricular outflow tract gradient by 49 mmHg compared to a 12 mmHg reduction with placebo at 30 weeks in patients with obstructive hypertrophic cardiomyopathy.