Real-world health status changes with mavacamten in symptomatic obstructive hypertrophic cardiomyopathy (oHCM) - Early findings from COMPASS-HCM

Background Pivotal clinical trials evaluating symptomatic patients with oHCM demonstrated significant improvements in symptoms, physical function, and quality of life with mavacamten. Whether such benefits occur in clinical practice is unknown. Purpose To assess longitudinal health status changes with the Kansas City Cardiomyopathy Questionnaire (KCCQ) and HCM Symptom Questionnaire (HCMSQ) within the first 12 weeks of mavacamten treatment in real-world United States (US) patients. Methods The COMPASS-HCM study recruited US adults with oHCM prescribed mavacamten. Key exclusion criteria included mavacamten treatment >7 days prior to enrollment, participants in clinical trials, moderate lung disease, hospitalization within 2 weeks, heart or lung surgery, or stroke/transient ischemic attack within 6 months that may impact health status. Patients were invited to complete KCCQ (higher is better) and HCMSQ (lower score is better) at baseline, weeks 2, 4, 8, 12, and then approximately every 12 weeks up to 2 years. Patient characteristics and changes in KCCQ and HCMSQ across different domains from baseline up to week 12 were described in patients who had not initiated mavacamten at baseline (mavacamten-naïve). Results Between May 2024 and January 2025, 102 patients were enrolled, completed baseline surveys, and began taking mavacamten, of whom 70 were mavacamten-naïve (mean [± SD] age 66.7 ± 11.9 years, 60% women, and 92.9% White race [Table 1]). At week 12, self-reported mavacamten doses were 2.5 mg in 16.1%, 5 mg in 74.2%, 10 mg in 6.5%, and 15 mg in 3.2% of patients. Treatment effects were observed as early as 2 weeks for both KCCQ and HCMSQ scores. Mean (±SD) 12-week improvements from baseline in KCCQ Overall Summary Score (OSS), Clinical Summary Score (CSS) (Figure 1A), and Quality of Life (QoL) scores were 16.0 ± 15.7, 13.0 ± 13.0, and 22.9 ± 22.5, respectively. At week 12, clinically meaningful KCCQ-OSS improvements of ≥ 5 points and ≥ 10 points were observed in 83.9% and 67.7% of patients, respectively (Figure 1B). Mean 12-week improvements from baseline were 3.1 ± 4.2 in the HCMSQ Shortness of Breath (SoB) score and 1.5 ± 2.4 in the Total score (Figure 1C). Conclusion(s) Real-world treatment of oHCM patients with mavacamten led to rapid improvements in symptoms, physical function, and overall quality of life as early as 2 weeks, mirroring data from clinical trials, with continued improvements through 12 weeks. These clinically meaningful changes in health status were seen despite the older age of patients than those enrolled in previous trials.