Abstract Body (Do not enter title and authors here):
Background: Mavacamten is approved for the treatment of adults with symptomatic obstructive hypertrophic cardiomyopathy (oHCM). In clinical studies of patients with oHCM, mavacamten has demonstrated improvements in peak VO2 compared to placebo. However, there is no approved therapy for symptomatic non-obstructive HCM (nHCM) patients. The ODYSSEY-HCM (NCT05582395) trial was conducted to evaluate clinical efficacy of mavacamten in adults with nHCM who remain symptomatic despite background therapy. In the current analysis from the ODYSSEY-HCM trial, we will report the changes in CPET parameters, from baseline to Week 48.

Methods: In this phase 3, randomized, double-blind, placebo-controlled, multi-center, international, parallel-group clinical trial in symptomatic nHCM, patients were assigned to placebo or mavacamten starting at 5 mg/day with down-titration to 1 mg or up-titration to 15 mg based on left ventricular ejection fraction (LVEF). Along with the dual-primary endpoints (change from baseline to Week 48 in peak oxygen consumption (pV02) assessed by cardiopulmonary exercise testing and Kansas City Cardiomyopathy Questionnaire-23 item Clinical Summary Score [KCCQ-23 CSS]), a detailed analysis of additional CPET parameters (change from baseline to Week 48) was performed.

Results: Out of 1043 patients screened, 580 were randomized (mean age 56±15 years, 46% women, and 43% with a family history of HCM). At baseline, all patients were nonobstructive, symptomatic (70% in New York Heart Association Class II and 30% Class III), 78% receiving β-blockers and mean LVEF 66±4, mean pV02 was 18±6 ml/kg/min and mean KCCQ-23 CSS of 57±20. The baseline respiratory exchange ratio was ≥ 1.0, mean VE/VCO2 slope was 37±9 with 312 (53.8%) patients performing bicycle ergometry, while the rest completed treadmill testing.

Conclusions: The ODYSSEY-HCM study was the largest randomized trial ever conducted in patients with nHCM. We will report the detailed results of analyses of CPET to better understand the disease at baseline, along with potential mechanistic insights into the impact of mavacamten on exercise performance in patients with nHCM.