Mavacamten is approved to treat adults with symptomatic obstructive hypertrophic cardiomyopathy (HCM). However, its effects in nonobstructive HCM remain uncertain. METHODS We conducted a phase 3, international, double-blind, placebo-controlled, clinical trial to determine whether mavacamten improves functional capacity and patient-reported health status among adults with symptomatic nonobstructive HCM. Patients were randomly assigned in a 1:1 ratio to receive mavacamten (starting at 5 mg per day and adjusted up to a maximum of 15 mg per day on the basis of left ventricular ejection fraction) or placebo (with sham dose adjustment) for 48 weeks. The two primary end points were the change from baseline to week 48 in peak oxygen uptake and in the 23-item Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS; scores range from 0 to 100, with higher scores indicating better health status). RESULTS We randomly assigned 289 patients to receive mavacamten and 291 to receive placebo. The mean (±SD) age of the patients was 56±15 years, and 46% were women. From baseline to week 48, the least-squares mean change in peak oxygen uptake was 0.52 ml per kilogram of body weight per minute (95% confidence interval [CI], 0.09 to 0.95) in the mavacamten group and 0.05 ml per kilogram per minute (95% CI, −0.38 to 0.47) in the placebo group (between-group difference, 0.47 ml per kilogram per minute; 95% CI, −0.03 to 0.98; P=0.07). The least-squares mean change in the KCCQ-CSS was 13.1 points (95% CI, 10.7 to 15.5) in the mavacamten group and 10.4 points (95% CI, 8.0 to 12.8) in the placebo group (between-group difference, 2.7 points; 95% CI, −0.1 to 5.6; P=0.06). Reductions in ejection fraction and interruptions in the trial regimen were more common with mavacamten than with placebo. CONCLUSIONS Among patients with nonobstructive HCM, mavacamten did not result in a significantly greater improvement in peak oxygen uptake or decrease in symptoms than placebo. (Funded by Bristol Myers Squibb; ODYSSEY-HCM ClinicalTrials.gov number, NCT05582395.)
Mavacamten in Symptomatic Nonobstructive Hypertrophic Cardiomyopathy / Desai, M.Y., Owens, A.T., Abraham, T., Olivotto, I., Garcia-Pavia, P., Lopes, R.D., Elliott, P., Fernandes, F., Verheyen, N., Maier, L., Meder, B., Azevedo, O., Kitaoka, H., Wolski, K., Wang, Q., Jaber, W., Mitchell, L., Myers, J., Rano, T., Gong, Z., et al.. - In: THE NEW ENGLAND JOURNAL OF MEDICINE. - ISSN 1533-4406. - STAMPA. - 393:(2025), pp. 961-972. [10.1056/NEJMoa2505927]
Mavacamten in Symptomatic Nonobstructive Hypertrophic Cardiomyopathy
Olivotto, Iacopo;
2025
Abstract
Mavacamten is approved to treat adults with symptomatic obstructive hypertrophic cardiomyopathy (HCM). However, its effects in nonobstructive HCM remain uncertain. METHODS We conducted a phase 3, international, double-blind, placebo-controlled, clinical trial to determine whether mavacamten improves functional capacity and patient-reported health status among adults with symptomatic nonobstructive HCM. Patients were randomly assigned in a 1:1 ratio to receive mavacamten (starting at 5 mg per day and adjusted up to a maximum of 15 mg per day on the basis of left ventricular ejection fraction) or placebo (with sham dose adjustment) for 48 weeks. The two primary end points were the change from baseline to week 48 in peak oxygen uptake and in the 23-item Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS; scores range from 0 to 100, with higher scores indicating better health status). RESULTS We randomly assigned 289 patients to receive mavacamten and 291 to receive placebo. The mean (±SD) age of the patients was 56±15 years, and 46% were women. From baseline to week 48, the least-squares mean change in peak oxygen uptake was 0.52 ml per kilogram of body weight per minute (95% confidence interval [CI], 0.09 to 0.95) in the mavacamten group and 0.05 ml per kilogram per minute (95% CI, −0.38 to 0.47) in the placebo group (between-group difference, 0.47 ml per kilogram per minute; 95% CI, −0.03 to 0.98; P=0.07). The least-squares mean change in the KCCQ-CSS was 13.1 points (95% CI, 10.7 to 15.5) in the mavacamten group and 10.4 points (95% CI, 8.0 to 12.8) in the placebo group (between-group difference, 2.7 points; 95% CI, −0.1 to 5.6; P=0.06). Reductions in ejection fraction and interruptions in the trial regimen were more common with mavacamten than with placebo. CONCLUSIONS Among patients with nonobstructive HCM, mavacamten did not result in a significantly greater improvement in peak oxygen uptake or decrease in symptoms than placebo. (Funded by Bristol Myers Squibb; ODYSSEY-HCM ClinicalTrials.gov number, NCT05582395.)
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