In patients with symptomatic hypertrophic obstructive cardiomyopathy (OHCM), long-term follow-up data presented last week at the European Society of Cardiology (ESC) Congress in London reinforce the established efficacy and safety profile of mavacamten, the first cardiac myosin inhibitor. With its inclusion in the European (ESC) and American (AHA/ACC) guidelines as a recommended option when symptoms persist after first-line therapy, mavacamten is therefore a standard of care for symptomatic OHCM.
The new long-term follow-up results – according to a note released by Bristol Myers Squibb (BMS) – refer to the Explorer-Lte cohort of the MAVA-Long-Term Extension (MAVA-LTE) study evaluating mavacamten in adult patients with oHCM, NYHA (New York Heart Association) class II-III. Patients experienced consistent and sustained improvements in echocardiographic measures and biomarkers after up to 3.5 years (180 weeks) of continuous treatment, including left ventricular outflow tract (LVOT) gradient at rest, LVOT gradient with Valsalva maneuver, indexed left atrial volume, and levels of the amino-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP). Improvement in symptoms and functional capacity as assessed by change in NYHA class and patient-reported outcomes (PROS) was also seen, including the majority of patients achieving NYHA class I. The safety profile of mavacamten up to 3.5 years remained consistent with that previously reported, with no new safety signals identified.
“The consistent and sustained improvements in cardiac parameters over 3 years with mavacamten,” said Pablo García-Pavia, MD, Head of the Hereditary Heart Diseases and Heart Failure Unit, Department of Cardiology, Puerta de Hierro University Hospital, and Professor at the Spanish Institute of Cardiovascular Research (CNIC), Madrid, Spain, “demonstrate how this therapy fills an important treatment need for patients with symptomatic obstructive HCM. These positive long-term data, together with the inclusion of mavacamten in the ESC clinical guidelines for obstructive HCM, underscore the important role of this drug in the long-term care of this lifelong condition that requires ongoing management.”
Specifically, at the cutoff date, 211 of 231 patients enrolled in the Mava-Lte study, a cohort of Explorer-Lte, were receiving mavacamten; 185 and 99 had reached weeks 156 and 180, respectively. Key findings from the Explorer-Lte data analysis showed sustained improvements in echocardiographic measures and biomarkers at weeks 156 and 180, compared to baseline. For echocardiographic parameters, patients experienced a 55.3 mmHg reduction in Valsalva Lvot gradient at both Week 156 and Week 180 and a 40.2 mmHg and 40.3 mmHg reduction in mean resting Lvot gradient at Week 156 and 180, respectively. Improvements in mean indexed left atrial volume from baseline were maintained at Weeks 144 and 180, with patients experiencing a 3.5 and 5.5 mL/m2 reduction, respectively. Mean left ventricular ejection fraction (Lvef) decreased by 11% from baseline at Week 180 and the mean (63.9%) remained within the normal range. Evaluation of biomarker data showed that median Nt-proBnp levels decreased by 504 ng/L at week 156 and by 562 ng/L at week 180.
At week 180, the majority of patients (66.3%) were in NYHA class I. Overall, 108 patients (46.8%) achieved a complete response, defined as achieving NYHA class I and a Valsalva manoeuvre Lvot gradient less than/equal to 30 mmHg during the study and maintained a complete response through the cut-off date. The PROS, measured by the Hcm Symptom Questionnaire (HCMSQ), showed an improvement in dyspnea score from baseline during the first 12 weeks, which was confirmed at weeks 156 and 180.
“These results, from the longest follow-up of the Phase 3 EXPLORER study to date,” said Roland Chen, Senior Vice President and Head of Immunology, Cardiovascular & Neuroscience (ICN) Development BMS, “further strengthen the established safety and efficacy profile of mavacamten. As the first and only cardiac myosin inhibitor approved for patients with symptomatic obstructive HCM and with thousands of patients worldwide treated to date, mavacamten, which targets the cause” of the disease, “is redefining the treatment landscape for this patient population.” The analysis of the EXPLORER-LTE study – the note concludes – did not reveal any new safety signals with mavacamten. A total of 20 patients (8.7%) experienced transient reductions in LVEF less than 50%; all returned to LVEF greater than or equal to 50% after treatment discontinuation and 14 patients restarted mavacamten.
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