Results from the phase 2 MAVERICK-HCM trial showed that treatment with mavacamten in patients with non-obstructive hypertrophic cardiomyopathy was well tolerated and reduced biomarkers of cardiac injury and wall stress, according to Dr Carolyn Y. Ho (Brigham and Women’s Hospital, USA) .
Mavacamten is a first-in-class, selective allosteric inhibitor of cardiac myosin, which reduces the number of myosin-actin cross bridges and decreases the excessive contractility that characterises hypertrophic cardiomyopathy. The MAVERICK-HCM study analysed 59 patients with symptomatic non-obstructive hypertrophic cardiomyopathy. After a 28-day screening period, patients were assigned to either once-daily mavacamten with a drug concentration target of 200 ng/mL (n=19), once-daily mavacamten with a drug concentration target of 500 ng/mL (n=21), or once-daily placebo (n=19). Patients were treated during a period of 16 weeks, followed by monitoring for 8 weeks after completion.
During treatment and wash-out (to 24 weeks), 89.7% of patients who received mavacamten had ≥1 treatment-emergent adverse event –76% had mild adverse events– versus 68.4% of patients on placebo. Furthermore, 10.3% of mavacamten patients had ≥1 serious adverse event versus 21.1% with placebo. Mean reduction in left ventricular ejection fraction from baseline to 16 weeks in the pooled mavacamten group was -4.1%. This was -2.3% for patients receiving 200 ng/mL mavacamten, -5.6% for those on 500 ng/mL mavacamten, and -2.3% for placebo. In addition, mavacamten reduced N-terminal pro-brain natriuretic peptide (NT-proBNP) by 53% compared with 1% with placebo (P=0.0005). The drug also decreased cardiac troponin I by 34% versus a 4% increase with placebo (P=0.009). The change in NT-proBNP at 4 weeks in patients assigned mavacamten correlated with the change in cardiac troponin I at 16 weeks (P=0.006). Dr Ho pointed out that patients with more severe disease may derive a greater benefit from treatment with mavacamten. The MAVERICK-HCM results set the groundwork for future larger-scale studies in non-obstructive hypertrophic cardiomyopathy and potentially heart failure with preserved ejection fraction.
- Ho CY, et al. Abstract 412-16. ACC/WCC 28-30 March 2020.
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