Real-world outcomes of mavacamten for symptomatic obstructive hypertrophic cardiomyopathy: global evidence from COLLIGO-HCM

Abstract Background / Introduction The mavaCamten ObservationaL evIdence Global cOnsortium in hypertrophic cardiomyopathy is a global observational study aiming to describe the real-world outcomes of treatments for obstructive HCM, including mavacamten. Participating sites from COLLIGO HCM were located in the United States, Canada, the United Kingdom, Australia, and Israel. Sites differed in requirements for genotyping and Risk Evaluation and Mitigation Strategies (REMS). Purpose To describe the effectiveness and safety of mavacamten in an international, real-world setting. Methods Retrospective data were collected from existing medical records and electronic registries. Patient characteristics, symptoms, echocardiography data, and adverse events were analyzed at baseline and varying follow-up. Results The COLLIGO-HCM cohort (N = 278) is a racially diverse population with 23.2% Black, 5.4% Asian, 4.3% Middle Eastern or North African participants, with a median follow-up duration of 29.3 weeks (IQR: 13.9-48.3 weeks). At baseline, 92.8% of patients (n=258) had some type of background medication (e.g., beta-blocker [BB] and/or calcium channel blocker [CCB], Table) at the time of mavacamten initiation and 7.2% (n=20) started mavacamten as monotherapy. Of those with some form of background medication, 26.4% (n = 68) discontinued at least one type of therapy, and 14.0% (n = 36) down titrated their background medication after mavacamten initiation (Fig Panel A). For those patients with follow up of at least 12 weeks, 66.5% (180 /208) of patients taking mavacamten had a NYHA classification of II or below, this proportion was 94.5% (153/162) for those with week 24 follow up and remained consistent throughout week 96 (Fig. Panel B). By week 24, most patients achieved mean left ventricular outflow tract obstruction (LVOT) gradients of ≤30 mm Hg both at rest and with Valsalva manoeuvre (90.3% and 76.8%, respectively), and 60.1% of patients achieved ≥ 1 NYHA class improvement by that time., Fig Panel C. Mean left ventricular ejection fraction (LVEF) post mavacamten initiation remained at or above 61% throughout follow-up (baseline value 66%). Temporary interruption of mavacamten due to LVEF ≤ 50% occurred in 11 (4%, 10 recovered and resumed treatment) patients and permanent discontinuation in 3 (1.1%, all recovered). Conclusions Findings from COLLIGO-HCM indicate that mavacamten is safe and effective in reducing LVOT obstruction and improving symptom burden in a racially diverse patient population treated in a real-world setting in 4 continents, with outcomes similar to those seen in more selected, clinical randomised controlled trials. The proportion of patients with LVEF ≤ 50% found in this study, including sites with and without REMS requirements, is aligned with the published safety profile of mavacamten.