Aficamten Shows Long-Term Safety and Cardiac Benefits in HCM Patients
核心洞察
Integrated safety analysis of aficamten across three clinical trials reinforces its robust safety profile, with adverse events similar to placebo.
FOREST-HCM analysis demonstrates successful withdrawal of standard of care medications in obstructive HCM patients treated with aficamten.
SEQUOIA-HCM data shows aficamten improves cardiac remodeling, structure, function, and biomarkers, suggesting potential disease modification.
Cytokinetics (搜索) presented new data at the European Society of Cardiology Congress 2024 in London, UK, highlighting the safety and long-term benefits of aficamten in patients with hypertrophic cardiomyopathy (搜索) (HCM). The presentations included integrated safety analyses and data on cardiac remodeling and symptom improvement.
Integrated Safety Analysis of Aficamten
An integrated safety analysis across the Phase 2 REDWOOD-HCM, Phase 3 SEQUOIA-HCM, and FOREST-HCM trials, involving 283 patients treated with aficamten and 153 with placebo, showed that aficamten was well-tolerated. The adverse event profile was similar to placebo. Stephen Heitner, M.D., Vice President, Head of Clinical Research, noted the promising safety and tolerability profile, suggesting potential for real-world use. Specifically, 3.9% of aficamten-treated patients experienced left ventricular ejection fraction (LVEF) <50%, but none had associated heart failure, and all were managed with dose adjustments. There were low incidences of new-onset atrial fibrillation (搜索) and myocardial infarction (搜索) compared to placebo.
Withdrawal of Standard of Care Medications
Data from the FOREST-HCM trial indicated that 93.8% of 145 patients with obstructive HCM were receiving standard of care (SoC) medications. Among the 47% of patients who attempted withdrawal of SoC medications, 92% were successful, with 64% discontinuing at least one SoC medication and 71% achieving monotherapy with aficamten. Ahmad Masri, M.D., M.S., Director of the Hypertrophic Cardiomyopathy (搜索) Center at Oregon Health and Science University, presented these findings, noting no statistically significant differences in aficamten's treatment effect post-withdrawal on key parameters like resting left ventricular outflow tract gradient (LVOT-G) and New York Heart Association (NYHA) Functional Class.
Cardiac Remodeling and Functional Improvements
Additional data from the SEQUOIA-HCM trial demonstrated favorable cardiac remodeling with aficamten treatment. A cardiac magnetic resonance (CMR) sub-study showed significant improvement in left ventricular mass index (LVMI) (-15.4 g/m2, p=0.001). Reductions were also observed in left ventricular maximal wall thickness (p<0.001), left atrial volume index (LAVI) (p<0.001), and extracellular volume mass index (ECVi) (p=0.014). Echocardiographic measures also improved, with approximately 60% improvement in gradients. Placebo-corrected resting LVOT-G improved by -40 mmHg (55 to 20 mmHg with aficamten) and Valsalva LVOT-G by -50 mmHg (86 to 35 mmHg with aficamten) with no significant adverse changes in LVEF (-4.8%, 95% CI -6.4 to -3.3; p<0.001).
Symptom Relief and Biomarker Improvements
Patients treated with aficamten experienced significant improvements in symptom burden and quality of life. The Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS) improved by 7.9 points (95% CI 4.8 to 11; p<0.001), and the Seattle Angina Questionnaire Summary Score (SAQ-SS) improved by 7.8 points (95% CI 4.7 to 11; p<0.001). Furthermore, aficamten led to an 80% reduction in NT-proBNP (p<0.001) and a 43% reduction in high-sensitivity cardiac troponin I (hs-cTnI) (p<0.001), indicating reduced cardiac wall stress and myocardial injury.