Consistent real world effectiveness of mavacamten across global regions in symptomatic obstructive hypertrophic cardiomyopathy: results from COLLIGO HCM

Background/Introduction Mavacamten is a cardiac myosin inhibitor that is approved in over 60 countries for the treatment of adults with symptomatic New York Heart Association (NYHA) class II–III obstructive hypertrophic cardiomyopathy (HCM). Labelling and regulatory requirements for mavacamten use differ across regions. A Risk Evaluation and Mitigation Strategy (REMS) is mandatory in the US, but not in Europe, where CYP2C19 metaboliser status may inform the starting dose of mavacamten; other countries require neither. COLLIGO-HCM is an international, multicentre study evaluating the real-world effectiveness and safety of mavacamten in patients with obstructive HCM. Purpose To determine the diversity of patients with obstructive HCM by examining outcomes following mavacamten treatment across geographic regions. Methods Patient-level data from 8 sites in 6 countries were stratified into 3 geographical groups: US; Europe (UK, Germany); and multi-regional (Australia, Canada, Israel). Data were analysed to assess patient characteristics, echocardiographic outcomes and safety at baseline and through 9 months of follow-up. Analyses used observed data only. Results Overall, 331 patients received mavacamten (US=198, Europe=65, multi-regional=68). Patient baseline characteristics varied across geographical groups (Table 1). European patients were older than US and multi-regional patients (mean age 64.3 vs 59.5 and 60.0 years). A higher proportion of European and multi-regional patients were male than US patients (66.2% and 60.3% vs 44.4%). The most common cardiovascular comorbidity was hypertension in US (69.2%) and European patients (38.5%), while hypertension (42.6%) and hyperlipidaemia (44.1%) were equally common in multi-regional patients. Resting left ventricular outflow tract (LVOT) gradient was similar across groups, but Valsalva LVOT gradient varied (mean 74.4, 89.8, and 99.7 mmHg in US, European and multi-regional patients, respectively). The proportion of patients in NYHA class III also varied across groups (42.6%, 50.0% and 30.9% in US, European and multi-regional patients, respectively). Significant and consistent improvements from baseline in resting and Valsalva LVOT gradient were observed from 3 months through 9 months of mavacamten treatment (Figure 1). Safety profile was consistent with clinical trials. Conclusions Although baseline characteristics and requirement for initiation varied across groups, significant and consistent improvements from baseline in LVOT gradients were observed. These findings suggest that the effectiveness and safety of mavacamten is predictable and consistent across different healthcare systems and patient populations.