Mavacamten and the Reframing of Obstructive Hypertrophic Cardiomyopathy as a Medically Treatable Disease
DOI:
https://doi.org/10.5281/zenodo.22344598Keywords:
Hypertrophic cardiomyopathy, Mavacamten, Cardiac myosin inhibitor, Left ventricular outflow tract obstruction, Septal reduction therapyAbstract
Until 2022, symptomatic obstructive hypertrophic cardiomyopathy (HCM) that failed beta-blockers or calcium-channel
blockers had one further destination: septal reduction therapy, either surgical myectomy or alcohol septal ablation, both
effective but both carrying a real procedural mortality. Mavacamten, a first-in-class cardiac myosin inhibitor, changed that
trajectory by directly targeting the excess actin-myosin cross-bridge formation that drives left ventricular outflow tract
(LVOT) obstruction. In the EXPLORER-HCM trial, 37% of mavacamten-treated patients met a composite
functional-and-symptomatic endpoint at 30 weeks versus 17% on placebo, with resting LVOT gradient falling by 47 mmHg
versus 10 mmHg. In VALOR-HCM, a trial enrolling patients already referred for septal reduction, only 17.9% of
mavacamten-treated patients still met septal-reduction-eligibility criteria at 16 weeks versus 76.8% on placebo, and at the
128-week open-label endpoint, 80.5% of patients had improved by at least one New York Heart Association class and only
15.7% still met eligibility criteria for septal reduction. This review sets out that evidence, the safety and monitoring framework
that has eased as post-marketing experience accumulated, and closes with the complication that qualifies mavacamten's
reframing of obstructive HCM as a medically treatable disease: at its US list price, the drug's own manufacturer-independent
cost-effectiveness assessment places it more than ten times above the conventional willingness-to-pay threshold, and the trial
evidence base itself still does not fully describe the broader real-world population now being prescribed it.
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