Abstract Body (Do not enter title and authors here): Background: Mavacamten is approved for the treatment of adults with symptomatic obstructive hypertrophic cardiomyopathy (oHCM). However, there is no approved therapy for symptomatic non-obstructive HCM (nHCM) patients. In the ODYSSEY-HCM trial (NCT05582395), mavacamten did not achieve statistically significant improvements in symptom score (KCCQ) or exercise capacity (pVO2) in symptomatic patients with nHCM. The symptomatic patients investigated in the ODYSSEY-HCM trial had evidence of severe disease. We conducted this post-hoc analyses to better understand the effect of baseline characteristics on clinical outcomes in the ODYSSEY-HCM trial.
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). During the trial, blood samples were collected to assess the exposure-response for the primary and secondary endpoints which included: change from baseline to Week 48 in peak oxygen consumption (pV02) assessed by cardiopulmonary exercise testing, Kansas City Cardiomyopathy Questionnaire-23 item Clinical Summary Score [KCCQ-23 CSS]), (N-terminal Pro Brain Natriuretic Peptide [NT-ProBNP], high-sensitivity troponin I (hs-cTnI]), and quality of life (Hypertrophic cardiomyopathy Symptom Questionnaire-Shortness of Breath [HCMSQ-SOB]).
Results: Out of 1043 patients screened, 580 are randomized (mean age 56±15 years, 46% women, and 43% with a family history of HCM). Baseline characteristics were as follows: symptomatic (70% in New York Heart Association Class II and 30% Class III), 78% receiving β-blockers, mean LVEF 66±4, mean pV02 was 18±6 ml/kg/min, mean KCCQ-23 CSS of 57±20, median NT-Pro BNP 918 ng/L (Interquartile range or IQR 463, 1725), median hs-cTnI 29.1 ng/dl (IQR 14.4, 91.7), and mean HCMSQ-SOB was 6±3.
Conclusions: The ODYSSEY-HCM study was the largest randomized trial ever conducted in nHCM patients. We will report on the detailed post-hoc analysis of response to mavacamten, based on pharmacokinetic distribution and disease severity.