Efficacy and Safety of Aficamten in Symptomatic Nonobstructive Hypertrophic Cardiomyopathy: Results From the REDWOOD-HCM Trial, Cohort 4

• Published in: Journal of cardiac failure 2024-11, Vol.30 (11), p.1439-1448
• Main Authors: MASRI, AHMAD, SHERRID, MARK V., ABRAHAM, THEODORE P., CHOUDHURY, LUBNA, GARCIA-PAVIA, PABLO, KRAMER, CHRISTOPHER M., BARRIALES-VILLA, ROBERTO, OWENS, ANJALI T., RADER, FLORIAN, NAGUEH, SHERIF F., OLIVOTTO, IACOPO, SABERI, SARA, TOWER-RADER, ALBREE, WONG, TIMOTHY C., COATS, CAROLINE J., WATKINS, HUGH, FIFER, MICHAEL A., SOLOMON, SCOTT D., HEITNER, STEPHEN B., JACOBY, DANIEL L., KUPFER, STUART, MALIK, FADY I., MENG, LISA, SOHN, REGINA L., WOHLTMAN, AMY, MARON, MARTIN S.
• Format: Article
• Language: English
• Subjects: Adult; aficamten; Aged; cardiac myosin inhibitor; Cardiomyopathy, Hypertrophic - drug therapy; Cohort Studies; Dose-Response Relationship, Drug; Echocardiography - methods; Female; Humans; Hypertrophic cardiomyopathy; Male; Middle Aged; Natriuretic Peptide, Brain - blood; nHCM; Peptide Fragments - blood; Stroke Volume - physiology; Treatment Outcome; Ventricular Function, Left - physiology
• ISSN: 1071-9164; 1532-8414; 1532-8414
• DOI: 10.1016/j.cardfail.2024.02.020

•Doses of aficamten were assessed for nonobstructive hypertrophic cardiomyopathy.•Treatment with aficamten was well tolerated.•Improvements in symptoms and angina were observed.•Changes in clinical status paralleled improvements in cardiac biomarkers.•Our findings support a larger pivotal phase 3 trial (ACACIA-HCM, NCT06081894). This open-label phase 2 trial evaluated the safety and efficacy of aficamten in patients with nonobstructive hypertrophic cardiomyopathy (nHCM). Patients with symptomatic nHCM (left ventricular outflow tract obstruction gradient ≤ 30 mmHg, left ventricular ejection fraction [LVEF] ≥ 60%, N-terminal pro-B-type natriuretic peptide [NT-proBNP] > 300 pg/mL) received aficamten 5–15 mg once daily (doses adjusted according to echocardiographic LVEF) for 10 weeks. We enrolled 41 patients (mean ± SD age 56 ± 16 years; 59% female). At Week 10, 22 (55%) patients experienced an improvement of ≥ 1 New York Heart Association class; 11 (29%) became asymptomatic. Clinically relevant improvements in Kansas City Cardiomyopathy Questionnaire Clinical Summary Scores occurred in 22 (55%) patients. Symptom relief was paralleled by reductions in NT-proBNP levels (56%; P < 0.001) and high-sensitivity cardiac troponin I (22%; P < 0.005). Modest reductions in LVEF (mean ± SD) of −5.4% ± 10 to 64.6% ± 9.1 were observed. Three (8%) patients had asymptomatic reduction in LVEF < 50% (range: 41%–48%), all returning to normal after 2 weeks of washout. One patient with prior history of aborted sudden cardiac death experienced a fatal arrhythmia during the study. Aficamten administration for symptomatic nHCM was generally safe and was associated with improvements in heart failure symptoms and cardiac biomarkers. ClinicalTrials.gov Identifier: NCT04219826 Summary of results from REDWOOD-HCM Cohort 4: Data in panel C are presented as mean and 95% CI; data in panel D are presented as mean and SD. Horizontal dotted lines represent the thresholds at which IP was down-titrated to the previous dosage (yellow) or was discontinued (red). CI, confidence interval; HCM, hypertrophic cardiomyopathy; hs-cTnI, high-sensitivity cardiac troponin T and I; KCCQ-CSS, Kansas City Cardiomyopathy Questionnaire clinical summary score; LVEF, left ventricular ejection fraction; LVOT, left ventricular outflow gradient; NT-proBNP, N-terminal pro B-type natriuretic peptide; NYHA, New York Heart Association; SD, standard deviation. [Display omitted]