Effect of Mavacamten on Chinese Patients With Symptomatic Obstructive Hypertrophic Cardiomyopathy: The EXPLORER-CN Randomized Clinical Trial

Key PointsQuestionWhat is the effect of treatment with mavacamten on Chinese patients with symptomatic obstructive hypertrophic cardiomyopathy? FindingsIn this phase 3 randomized clinical trial of 81 patients, mavacamten significantly improved Valsalva left ventricular outflow tract obstruction compared with placebo and was well tolerated. New York Heart Association functional class, health status, cardiac biomarkers, and cardiac structure were also improved. MeaningThe clinical benefits of mavacamten for Chinese patients with symptomatic obstructive hypertrophic cardiomyopathy were consistent with previous data; mavacamten offers a new option for an underrepresented population for whom there is an important unmet medical need. ImportanceMavacamten has shown clinical benefits in global studies for patients with obstructive hypertrophic cardiomyopathy (oHCM), but evidence in the Asian population is lacking. ObjectiveTo evaluate the safety and efficacy of mavacamten compared with placebo for Chinese patients with symptomatic oHCM. Design, Setting, and ParticipantsThis phase 3, randomized, double-blind, placebo-controlled clinical trial was conducted at 12 hospitals in China. Between January 4 and August 5, 2022, patients with oHCM and a left ventricular outflow tract (LVOT) gradient of 50 mm Hg or more and New York Heart Association (NYHA) class II or III symptoms were enrolled and received treatment for 30 weeks. InterventionsPatients were randomized 2:1 to receive mavacamten (starting at 2.5 mg once daily) or placebo for 30 weeks. Main Outcomes and MeasuresThe primary end point was change in Valsalva LVOT peak gradient from baseline to week 30. Left ventricular outflow tract gradients and left ventricular ejection fraction (LVEF) were assessed by echocardiography, while left ventricular mass index (LVMI) was determined by cardiac magnetic resonance imaging. Analysis was performed on an intention-to-treat basis. ResultsA total of 81 patients (mean [SD] age, 51.9 [11.9] years; 58 men [71.6%]) were randomized. Mavacamten demonstrated a significant improvement in the primary end point compared with placebo (least-squares mean [LSM] difference, -70.3 mm Hg; 95% CI, -89.6 to -50.9 mm Hg; 1-sided P<.001). Similar trends were demonstrated for resting LVOT peak gradient (LSM difference, -55.0 mm Hg; 95% CI, -69.1 to -40.9 mm Hg). At week 30, more patients receiving mavacamten than placebo achieved a Valsalva LVOT peak gradient less than 30 mm Hg (48.1% [26 of 54] vs 3.7% [1 of 27]), less than 50 mm Hg (59.3% [32 of 54] vs 7.4% [2 of 27]), and NYHA class improvement (59.3% [32 of 54] vs 14.8% [4 of 27]). Greater improvements were also observed with mavacamten regarding the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (LSM difference, 10.2; 95% CI, 4.4-16.1), N-terminal pro-B-type natriuretic peptide level (proportion of geometric mean ratio, 0.18; 95% CI, 0.13-0.24), high-sensitivity cardiac troponin I level (proportion of geometric mean ratio, 0.34; 95% CI, 0.27-0.42), and LVMI (mean difference, -30.8 g/m(2); 95% CI, -41.6 to -20.1 g/m(2)). Safety and tolerability were similar between mavacamten and placebo. No patients experienced LVEF less than 50%. ConclusionsMavacamten significantly improved Valsalva LVOT gradient vs placebo for Chinese patients. All secondary efficacy end points were also improved. Mavacamten was well tolerated with no new safety signals. This study supports the efficacy and safety of mavacamten in diverse populations, including Chinese patients. Trial RegistrationClinicalTrials.gov Identifier: NCT05174416 This randomized clinical trial evaluates the safety and efficacy of mavacamten compared with placebo for Chinese patients with symptomatic obstructive hypertrophic cardiomyopathy.