Phase 3 Open-Label Study Evaluating the Efficacy and Safety of Mavacamten in Japanese Adults With Obstructive Hypertrophic Cardiomyopathy ― The HORIZON-HCM Study ―
Year: 2024
Type: article
Study design: Clinical Trial
Abstract: BACKGROUND: Mavacamten, a cardiac myosin inhibitor, significantly improved symptoms and cardiac function vs. placebo in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM) in EXPLORER-HCM. However, the efficacy and safety profiles of mavacamten in Japanese patients are unclear. METHODS AND RESULTS: HORIZON-HCM is a Phase 3 single-arm study in Japanese patients with symptomatic obstructive HCM. The mavacamten starting dose was 2.5 mg; individualized dose titration occurred in Weeks 6-20 based on Valsalva left ventricular outflow tract (LVOT) gradient and resting left ventricular ejection fraction (LVEF). Overall, 38 patients were treated; 36 completed the 30-week primary treatment analysis period. Clinically significant improvements in postexercise LVOT gradient were observed after 30 weeks of treatment (mean change from baseline -60.7 mmHg). Improvements in N-terminal pro B-type natriuretic peptide, New York Heart Association class, and Kansas City Cardiomyopathy Questionnaire-23 Clinical Summary Score were observed over 30 weeks, and mean LVEF was ≥74% at all visits. Treatment-emergent adverse events (TEAEs) and serious TEAEs were reported in 63.2% and 7.9% of patients, respectively; none resulted in treatment discontinuation. One patient experienced a transient asymptomatic reduction in LVEF to <50%. No deaths occurred during the study. CONCLUSIONS: In Japanese patients with obstructive HCM, mavacamten was associated with similar improvements in LVOT gradients, cardiac biomarkers, and symptoms to those observed in EXPLORER-HCM. Treatment was well tolerated with no new safety concerns.
Source: Circulation Journal
Authors: Hiroaki Kitaoka, Masaki Ieda, Mio Ebato, Ken Kozuma, Morimasa Takayama, Kaoru Tanno, Nobuyuki Komiyama, Yasushi Sakata, Yuichiro Maekawa, Yuichiro Minami, Akiyoshi Ogimoto, Tomofumi Takaya, Satoshi Yasuda, Eisuke Amiya, Yutaka Furukawa, Tetsuya Watanabe, Daigo Hiraya, Hidetaka Miyagoshi, Gen Kinoshita, Alison Reedy, Sheila M. Hegde, Victoria Florea, Chisato Izumi
Institutions: University of Kochi, Kōchi University, Keio University, SHOWA Medical University Fujigaoka Hospital, Teikyo University Hospital, Sakakibara Hospital, SHOWA Medical University Koto Toyosu Hospital, St. Luke's International Hospital, The University of Osaka, Hamamatsu University, Hamamatsu University School of Medicine, Tokyo Women's Medical University, Uwajima City Hospital, Uwajima Hospital, Hyogo Prefectural Harima-Himeji General Medical Center, Tohoku University, The University of Tokyo, Kobe City Medical Center General Hospital, Osaka Prefectural Medical Center, University of Tsukuba, Bristol-Myers Squibb (United States), Brigham and Women's Hospital, National Cerebral and Cardiovascular Center
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4404095973