Mavacamten treatment in obstructive hypertrophic cardiomyopathy for up to 30 weeks: An integrated analysis of cardiac magnetic resonance data from a diverse population in randomized clinical trials

Abstract Background Mavacamten, the first-in-class cardiac myosin inhibitor, is approved for the treatment of patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM). Previous cardiac magnetic resonance (CMR) imaging analyses in individual clinical trials indicated that mavacamten treatment was associated with positive cardiac structural remodelling. Purpose To evaluate cardiac structural remodelling and clinical correlations in a diverse population of patients with symptomatic obstructive HCM treated with mavacamten for 30 weeks, based on an integrated analysis of CMR data from randomized controlled trials (RCTs) conducted globally. Methods An integrated CMR analysis of double-blind RCTs was conducted using data from both the EXPLORER-HCM (NCT03470545; international) and EXPLORER CN trials. Changes from baseline to week 30 in CMR parameters were assessed by treatment group (MAVA-RCT and Placebo-RCT) in pooled patient populations. Clinical correlations were assessed between changes from baseline in CMR parameters (left ventricular mass index [LVMI] and left atrial volume index [LAVI]) and biomarker levels (N-terminal pro B-type natriuretic peptide [NT-proBNP] and troponin I). Trends were compared in patients who received 30 weeks of mavacamten treatment in the open label HORIZON-HCM study. Results Overall, 93 patients were pooled from the double-blind studies (MAVA-RCT: 56; Placebo-RCT: 37) and 17 patients were assessed from HORIZON-HCM. At baseline, for the MAVA-RCT vs Placebo-RCT group, mean age was 53.6 years vs 56.2 years, 71.4% vs 62.2% were male, 71.4% vs 54.1% were Asian and 28.6% vs 45.9% were White. Greater reductions from baseline were observed for MAVA-RCT than for Placebo-RCT in LVMI (mean difference [95% confidence interval (CI)]: −25.2 [−28.3, −16.3] g/m2), LAVI (mean difference [95% CI]: −15.6 [−18.2, −8.3] mL/m2), left ventricular (LV) maximum wall thickness (mean difference [95% CI]: −3.1 [−3.7, −2.0] mm), LV end-diastolic volume index (mean difference [95% CI]: −7.2 [−11.9, −3.3] mL/m2) and LV ejection fraction (mean difference [95% CI]: −4.1 [−6.6, −1.5]%) (Table). Similar reductions from baseline to week 30 were observed in mavacamten-treated patients in HORIZON-HCM. For the MAVA-RCT group, reductions from baseline to week 30 in LVMI were correlated with reductions in NT-proBNP (correlation coefficient: 0.48) and troponin I (correlation coefficient: 0.38) (Figure); correlations were also observed between reductions in LAVI and reductions in NT-proBNP (correlation coefficient: 0.28) and troponin I (correlation coefficient: 0.27). Conclusion This integrated analysis of CMR data from RCTs confirmed that mavacamten treatment over 30 weeks is associated with positive cardiac structural remodelling which correlates with improvements in clinical biomarkers in a diverse population of patients with symptomatic obstructive HCM.