Abstract Body (Do not enter title and authors here): Introduction: Treatment with aficamten in patients with obstructive HCM (oHCM) led to significant improvements in patient-reported outcomes (PROs) over 24 weeks in the pivotal SEQUOIA-HCM trial. The aim of this analysis was to provide a comprehensive evaluation of the long-term effects of aficamten across multiple PROs in the open-label extension trial FOREST-HCM (NCT04848506).

Methods: Patients completing an aficamten parent study were offered participation in FOREST-HCM. Patients completing ≥48 weeks in FOREST-HCM as of August 31, 2024 were included. The Kansas City Cardiomyopathy Questionnaire (KCCQ), Seattle Angina Questionnaire 7-item (SAQ-7), and EuroQol Five-Dimensional Questionnaire (EQ-5D-5L) index and visual analog scale (VAS) were administered at baseline and at Weeks 12, 24, 36, and 48. The patient global impression of change (PGI-C) survey was administered at Weeks 12, 24, 36, and 48. Mixed models for repeated measures were used to analyze changes in mean KCCQ summary scores (including the Clinical Summary Score [CSS] and Overall Summary Score [OSS]), SAQ-7 summary scores, and EQ-5D-5L index and VAS scores from baseline to 48 weeks. Associations among PROs and between PROs and clinical measures of HCM severity were evaluated using Spearman correlation coefficients.

Results: As of August 2024, 182 patients (mean age 60.2 [SD ±13.1] years, 56% were male) had reached 48 weeks of follow-up. Significant improvements in all PROs were observed by Week 12 and sustained through Week 48 (Figure). Least-squares mean differences (95% CI) between the KCCQ-CSS and -OSS from baseline to 48 weeks were 16.1 (14.4–17.7) and 19.1 (17.3–21.0), respectively (P<0.0001), with the largest gains in the quality-of-life (QoL) domain (26.0 [23.3–28.6]; P<0.0001). The SAQ-7 summary score increased by 17.7 (15.5–19.8; P<0.0001), with a 22.4-point gain (19.1–25.6; P<0.0001) in the QoL domain. EQ-5D-5L index and VAS scores improved by 0.12 (0.10–0.14) and 13.4 (11.6–15.2), respectively (P<0.0001). At 48 weeks, 77% of patients reported feeling “Much Improved” or “Very Much Improved” on the PGI-C. Improvements in PROs were significantly correlated with important clinical measures of oHCM severity (Table).

Conclusions: Aficamten led to significant and sustained improvements in PROs in patients with oHCM. The improvement was seen across all symptom domains, particularly QoL, and correlated with important clinical measures of disease severity.