Late-breaking phase III data demonstrating health status benefits of mavacamten in patients with obstructive hypertrophic cardiomyopathy.- BMS

Bristol Myers Squibb announced a new analysis of data from the Phase III EXPLORER-HCM study evaluating mavacamten, an investigational, first-in-class cardiac myosin inhibitor, in patients with obstructive hypertrophic cardiomyopathy (oHCM), which was presented at the American College of Cardiology’s 70th Annual Scientific Session (ACC.21), with simultaneous publication in The Lancet. At 30 weeks, the change in Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ OSS) was greater in mavacamten patients than placebo, with similar benefits across all KCCQ subscales. Moreover, a greater proportion of mavacamten patients achieved a very large, clinically meaningful improvement ( greater than 20 points) in the KCCQ OSS, compared to placebo, 36% [33/92] vs. 15% [13/88]. A change of at least 5 points is required to be considered clinically significant. These results were presented as part of the Featured Clinical Research I Session (403-09) in the Hot Topics Channel from 12:15-1:30 p.m. EDT. In the Phase III, double-blind, placebo-controlled trial, patients with symptomatic oHCM (LVOT gradient greater than 50 mmHg and NYHA Class II-III) were randomized 1:1 to mavacamten (n=123) or placebo (n=128) for 30 weeks, followed by an 8-week washout. The KCCQ was administered at baseline and Weeks 6, 12, 18, 30 and 38. Change from baseline in KCCQ scores were analyzed using mixed model repeated measures and responder analyses. A total of 92 patients randomized to mavacamten and 88 randomized to placebo completed the KCCQ at both baseline and Week 30 (end of treatment). Findings include : i. At 30 weeks, the change in KCCQ OSS was greater with mavacamten than placebo (mean ± SD, 14·9±16 vs. 5·4±14; difference=9·1 (95%CI: 5·5-12·8; p<0·001), with similar benefits across all kccq subscales. ii. the proportion of patients with a very large change (kccq oss greater than 20 points) was 36% [33 92] vs. 15% [13 88], with an estimated absolute difference of 21% (95% ci="8·8%," 33·4%) and number needed to treat of 5 (95% ci="3," 11). a change of at least 5 points is considered clinically important. these gains returned to baseline after active treatment was stopped. iii. a greater proportion of patients in the placebo arm had no change or deterioration in their health status at week 30. see-"mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (explorer-hcm): health status analysis of a randomised, double-blind, placebo-controlled, phase 3 trial"- prof john a spertus, md. jennifer t fine, phd. prof perry elliott, md. et al. published:may 15, 2021doi:https: doi.org 10.1016 s0140-6736(21)00763-7.>