Trial Shows No Meaningful Gains With Mavacamten In Nonobstructive Hypertrophic Cardiomyopathy

Mavacamten curen astatine 48 weeks was not associated pinch important improvements successful patient-reported wellness position aliases highest oxygen depletion compared pinch placebo successful patients pinch symptomatic nonobstructive hypertrophic cardiomyopathy, according to late-breaking investigation presented successful a Hot Line convention coming astatine ESC Congress 2025 and simultaneously published successful New England Journal of Medicine.

Nonobstructive hypertrophic cardiomyopathy (HCM) is a information wherever nan bosom musculus thickens, but this thickening does not importantly artifact humor travel retired of nan heart. In contrast, successful obstructive HCM, nan thickened portion of nan bosom musculus blocks humor flow. Both forms of HCM tin worsen complete time, causing symptoms for illustration shortness of breath, fatigue and thorax pain. HCM tin lead to bosom failure, arrhythmias and besides rarely, abrupt cardiac death.

Principal Investigator, Professor Milind Desai from Cleveland Clinic, Cleveland, USA, explained why nan ODYSSEY-HCM proceedings was carried out: "There are presently nary approved aesculapian therapies for patients pinch nonobstructive HCM, who acquisition a precocious load of symptoms. The cardiac myosin inhibitor, mavacamten, is approved for nan curen of symptomatic obstructive HCM and results from a mini shape II study suggested improvements successful biomarkers successful nonobstructive HCM. We conducted nan shape III ODYSSEY-HCM proceedings to measure whether mavacamten improved patient-reported wellness position and functional capacity successful patients pinch symptomatic nonobstructive HCM."

This randomised, double-blind, parallel-group shape III proceedings was conducted astatine 201 sites successful 22 countries. Symptomatic big patients pinch nonobstructive HCM were enrolled pinch cardinal inclusion including: highest near ventricular outflow tract gradient <30 mmHg astatine remainder and <50 mmHg pinch provocation, New York Heart Association (NYHA) functional people II aliases III, Kansas City Cardiomyopathy Questionnaire 23-item Clinical Summary Score (KCCQ-23 CSS) ≤85, near ventricular ejection fraction (LVEF) ≥60% and elevated biomarkers. Patients were randomized 1:1 to receive mavacamten 5 mg (with blinded dose titration arsenic needed based connected LVEF) aliases placebo erstwhile regular for 48 weeks. The 2 superior endpoints were nan alteration from baseline to week 48 successful patient-reported wellness position (measured by nan KCCQ-23 CSS) and successful highest oxygen consumption.

Among 580 patients randomised, nan mean property was 56 years and 46% were women. The mean clip from nan first test to randomisation was 10.3 years and 43.3% of patients had a family history of HCM.

There were nary important differences successful nan dual superior endpoints pinch mavacamten vs. placebo astatine week 48. KCCQ-23 CSS accrued by 13.1 (95% assurance interval [CI] 10.7 to 15.5) successful nan mavacamten group and 10.4 (95% CI 8.0 to 12.8) successful nan placebo group (between-group quality 2.7; 95% CI -0.08 to 5.6; p=0.056). The least-squares mean summation successful highest oxygen depletion was 0.52 (95% CI 0.09 to 0.95) successful nan mavacamten group and 0.05 (95% CI -0.38 to 0.47) successful nan placebo group (between group-difference 0.47 ml/kg/min; 95% CI -0.03 to 0.98; p=0.066). The secondary endpoints did not meet nan request for further statistical testing.

Regarding safety, treatment-emergent adverse events resulting successful study supplier interruption aliases imperishable curen discontinuation occurred successful 14.6% and 5.2% of patients, respectively, pinch mavacamten and 5.2% and 2.8% of patients, respectively, pinch placebo. LVEF <50% occurred successful 21.5% of patients successful nan mavacamten group vs. 1.7% of patients successful nan placebo group, and each but 3 patients returned to LVEF ≥50% aft study supplier interruption.

In this ample proceedings including patients pinch longstanding nonobstructive HCM, important improvements successful patient-reported wellness position aliases highest oxygen depletion were not observed pinch mavacamten. Further analyses are being conducted, including 2 that will beryllium presented astatine ESC Congress 2025 connected Sunday to understand much astir nan effects of mavacamten successful nonobstructive HCM and whether immoderate diligent subgroups whitethorn benefit."

Professor Milind Desai from Cleveland Clinic, Cleveland, USA