Mavacamten effectiveness and safety in the real-world setting and association with CYP2C19 metaboliser status: data from a canadian prospective registry
S Moussa, M F Gauthier, I Henarejos Castillo, S Corriveau, J Ennaciri, I Mongrain, P Garceau, P Lavoie-L'allier, M Tremblay-Gravel, J Boulet, G Giraldeau, J Cadrin-Tourigny, C Steinberg, T Roston, R TadrosAbstract
Introduction
Patients with obstructive hypertrophic cardiomyopathy (oHCM) have been historically treated using non-specific pharmacologic therapy, followed by invasive septal reduction therapy (SRT) if obstruction persists. A first-in-class selective cardiac myosin inhibitor, mavacamten was first approved in 2022 for oHCM treatment.
Purpose
This study sought to 1) describe the patient population, dosing patterns, effectiveness and safety of mavacamten in the real-world setting in a Canadian HCM population included in the ongoing national HiRO-HCM registry, and 2) explore association of CYP2C19 phenotype with obstruction and left ventricular ejection fraction (LVEF).
Methods
Patients enrolled in the HiRO-HCM Registry who had initiated mavacamten treatment as part of routine care at our Institute were included. As of December 2025, 245 (11%) of the 2230 patients enrolled in the registry had received mavacamten, of whom 162 (66%) were treated at MHI. Data up to 24 months prior to drug initiation (baseline) and from clinical follow-up (at 1, 3, 6, 12 months and annually thereafter) was collected. Efficacy was assessed using left ventricular outflow tract (LVOT) gradient and New York Heart Association (NYHA) class. Tolerability was assessed using treatment interruptions (temporary) or discontinuations (permanent) for LVEF<50% or other reasons. Effectiveness and safety were described overall, and for CYP2C19 subgroups based on a posteriori DNA analysis.
Results
Data analysis of 147 consecutive patients having initiated mavacamten was conducted (age 62 ± 13 years, 42% female). At initiation, 13% of patients were on mavacamten monotherapy, increasing to 19% at 12 months. Patients had a Valsalva LVOT gradient of 83 ± 39 mmHg at baseline which decreased to 28 ± 31 mmHg at 12 months (Figure 1A). NYHA class significantly improved over time with 51% and 43% of patients in NYHA class 1 and 2, respectively, at 12 months (Figure 1B). Patients were followed for a median time of 15 months. Ten (6.8%) patients discontinued mavacamten due to LVEF<50% and an additional 8 (5.4%) discontinued it for other reasons, mainly due to side effects (n=6). Additionally, CYP2C19 phenotype was significantly associated with efficacy (resting gradient<30mmHg) at 1 month (Cochran-Armitage test for trend p<0.05) but not at 12 months (p=0.2) (Figure 2A). Association of CYP2C19 phenotype with LVEF<50% was also not statistically significant (Figure 2B).
Conclusion
This Canadian observational study of mavacamten in oHCM provides evidence of the efficacy and safety of the drug in a real-world setting, as was observed in clinical trials. Consistent tolerability was observed in CYP2C19 metaboliser groups, while variability in response at 1 month associated with metaboliser status suggests a potential for genotyping to optimize dose titration earlier.For image description, please refer to the figure legend and surrounding text.For image description, please refer to the figure legend and surrounding text.