Clinical benefits of mavacamten demonstrated in patients with symptomatic obstructive hypertrophic cardiomyopathy
1. Mavacamten demonstrated substantial enhancement in alleviating valsalva left ventricular outflow tract (LVOT) obstruction in Chinese patients with symptomatic obstructive hypertrophic cardiomyopathy (oHCM) compared to placebo, with favorable tolerability.
2. Additionally, all secondary measures of effectiveness, including New York Heart Association (NYHA) functional class, health status, cardiac biomarkers, and cardiac structure, displayed improvements.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Alleviating LVOT obstruction is a key therapeutic objective for individuals with oHCM. Mavacamten, an innovative, selective, and reversible allosteric inhibitor of β-cardiac myosin, exhibited a significant reduction in LVOT gradient and enhancement in exercise capacity, NYHA functional class, and overall health status during the global phase 3 EXPLORER-HCM trial for patients with oHCM. Nonetheless, limited clinical evidence exists concerning the effectiveness and safety of mavacamten for Asian patients. This study assessed the efficacy and safety of mavacamten in patients diagnosed with oHCM. This randomized control trial found that in Chinese patients with oHCM, mavacamten led to a significant enhancement in the LVOT gradient compared to the placebo by the 30th week. One limitation of this study is the modest sample size. Subsequent research involving a more extensive participant pool and an extended follow-up duration can provide more robust and comprehensive insights into the efficacy and safety of the treatment. In conclusion, the safety profile exhibited by mavacamten remained consistent with prior research. These findings hold significance as they provide evidence that the effectiveness and safety of mavacamten apply to Asian patients, specifically individuals of Chinese descent.
Click to read the study in JAMA Cardiology
Click to read an accompanying editorial in JAMA Cardiology
Relevant Reading: Hypertrophic Cardiomyopathy: New Concepts and Therapies
In-Depth [randomized controlled trial]: This study was a phase 3, randomized, double-blind, placebo-controlled trial that included 81 patients from 12 hospitals in China between January 4 – August 5, 2022. Patients were deemed eligible for inclusion if they were 18 years of age or older, weighing above 45 kg, and diagnosed with oHCM, characterized by a resting peak LVOT gradient of 50mmHg or higher, either at rest or following valsalva maneuver, along with a left ventricular ejection fraction (LVEF) equal to or greater than 55%, and classified as NYHA class II or III. The main objective focused on altering the peak gradient of the LVOT during valsalva maneuver, assessed through Doppler echocardiography, from the study’s outset to the 30-week mark. Secondary measures of effectiveness included the percentage of patients at week 30 who exhibited a valsalva LVOT peak gradient below 30mmHg, a valsalva LVOT peak gradient below 50 mm Hg, a minimum of one class advancement in NYHA functional classification, as well as alterations from baseline to week 30. Following a treatment duration of 30 weeks, mavacamten exhibited a notable enhancement in the primary endpoint in contrast to the placebo (least-squares mean [LSM] difference, −70.3mmHg; 95% CI, −89.6 to −50.9 mm Hg; 1-sided P < 0.001). All secondary effectiveness measures also exhibited improvement. Mavacamten was determined to be as tolerable and safe as the placebo after measuring key safety indicators such as incidence and severity of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs).
Image: PD
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