EXPLORER-CN week 78: langetermijneffect en veiligheid van mavacamten bij Chinese patiënten met obstructieve HCM

BACKGROUND: Long-term efficacy and safety of mavacamten in Chinese patients with obstructive hypertrophic cardiomyopathy are unknown. METHODS: Patients who completed the 30-week, double-blind, placebo-controlled treatment period in EXPLORER-CN (A Study to Evaluate the Efficacy and Safety of Mavacamten in Chinese Adults With Symptomatic Obstructive HCM), with no active safety concerns, were eligible to enter the long-term extension period to receive 48-week mavacamten treatment. Patients previously on mavacamten continued mavacamten (dose at week 30; mavacamten-mavacamten group); patients previously on placebo received mavacamten (starting dose, 2.5 mg once daily; placebo-mavacamten group). Key efficacy end points included change from baseline in echocardiographic measures, New York Heart Association functional class, 23-item Kansas City Cardiomyopathy Questionnaire Clinical Summary Score, and cardiac biomarkers through week 78. Analyses were descriptive; no between-group hypothesis testing was performed. RESULTS: Seventy-nine patients (mean age, 51.6 years; 27.8% women) entered the long-term extension period (mavacamten-mavacamten, n=54; placebo-mavacamten, n=25). In the mavacamten-mavacamten group, numerical improvements in Valsalva and resting left ventricular outflow tract peak gradients were maintained through week 78 (mean change from baseline, -73.0 mm Hg [95% CI, -86.4 to -59.5]; and -56.3 mm Hg [95% CI, -67.1 to -45.5], respectively). Numerical improvements were also observed for other echocardiographic parameters, New York Heart Association class, Kansas City Cardiomyopathy Questionnaire Clinical Summary Score, and cardiac biomarkers through week 78. In the placebo-mavacamten group, numerical improvements with mavacamten in these parameters were noted from week 30 to week 78. Long-term mavacamten treatment appeared well tolerated; left ventricular ejection fraction <50% was rare. CONCLUSIONS: In this exploratory long-term extension study, 78-week mavacamten treatment appeared well-tolerated and was associated with numerical improvements from baseline in echocardiographic parameters, New York Heart Association class, patient-reported health status, and cardiac biomarkers in Chinese patients with obstructive hypertrophic cardiomyopathy. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT05174416.