Hypertrophic cardiomyopathy (HCM) has, for the first time, a class of drugs that targets its core pathophysiology rather than just its symptoms: the cardiac myosin inhibitors, which reduce the excessive actin-myosin cross-bridging that drives hypercontractility and outflow obstruction.
Cardiac myosin inhibitors
Mavacamten (Camzyos) was the first-in-class agent, FDA-approved in 2022 on the strength of the EXPLORER-HCM and VALOR-HCM trials. It reduces left ventricular outflow tract gradients and improves symptoms in obstructive HCM and is indicated for patients with persistent symptoms despite maximally tolerated beta-blockers and/or calcium channel blockers. Because it can reduce ejection fraction, it is dispensed under a REMS program with regular echocardiographic monitoring.
The major update is aficamten (Myqorzo), the next-in-class myosin inhibitor, which was FDA-approved in December 2025 (with approvals in China and, in early 2026, the EU). Its pivotal SEQUOIA-HCM trial met the primary endpoint — improving peak oxygen uptake by about 1.7–1.8 mL/kg/min versus placebo — and improved all key secondary endpoints including NYHA class and Kansas City Cardiomyopathy Questionnaire scores. Crucially, the head-to-head MAPLE-HCM trial showed aficamten superior to metoprolol, challenging the long-standing reliance on beta-blockers as first-line therapy. Aficamten is also dispensed under a REMS program and is in Phase 3 evaluation (ACACIA-HCM) for non-obstructive HCM.
Conventional therapy and procedures
Beta-blockers, calcium channel blockers, and disopyramide remain useful for symptom control but do not alter disease course. For drug-refractory obstruction, septal reduction therapy (surgical myectomy or alcohol septal ablation) remains an option. Gene- and RNA-based therapies targeting the underlying sarcomere mutations are under investigation.
| Agent | Status | Key evidence |
|---|---|---|
| Mavacamten (Camzyos) | Approved 2022 | EXPLORER-HCM, VALOR-HCM; reduces LVOT gradient and symptoms |
| Aficamten (Myqorzo) | Approved 2025 | SEQUOIA-HCM (placebo); MAPLE-HCM (superior to metoprolol) |
Both require REMS enrollment and echocardiographic monitoring for reduced ejection fraction.
Further reading: SEQUOIA-HCM aficamten (Maron et al., NEJM 2024) and MAPLE-HCM (2025); aficamten FDA approval (December 2025); medical therapies for HCM (Desai et al., 2023); 2022 AHA/ACC HCM guideline (Ommen et al.).