お知らせ • May 07
Cytokinetics Incorporated Announces Positive Topline Results From Acacia-Hcm, The Pivotal Phase 3 Clinical Trial Of Aficamten In Patients With Non-Obstructive Hypertrophic Cardiomyopathy
Cytokinetics, Incorporated (Nasdaq: CYTK) announced positive topline results from ACACIA-HCM (Assessment Comparing Aficamten to Placebo on Cardiac Endpoints In Adults with Non-Obstructive HCM), the pivotal Phase 3 clinical trial of aficamten in patients with symptomatic non-obstructive hypertrophic cardiomyopathy (HCM). ACACIA-HCM met both dual primary endpoints, demonstrating statistically significant improvements from baseline to Week 36 compared to placebo in both Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) and maximal exercise performance (pVO2). Table 1: Primary Endpoint Results Primary Endpoints Change from Baseline to Week 36 Aficamten vs Placebo p-value LSM (95% CI) LSM (95% CI) Aficamten Placebo KCCQ-CSS 11.4 (9.6 – 13.2) 8.4 (6.6 – 10.2) 3.0 (0.5 - 5.5) 0.021 pVO2 (mL/kg/min) 0.64 (0.32 – 0.95) -0.03 (-0.35 – 0.28) 0.67 (0.22 - 1.1) 0.003 LSM = least square mean; CI = confidence interval The improvement in KCCQ was robust and consistent throughout the treatment period in participants on aficamten. Following washout, KCCQ decreased for participants on aficamten to match the placebo group. At Week 36, pVO2 increased for participants on aficamten, while it remained unchanged for participants on placebo, consistent with prior trials of aficamten in obstructive HCM (oHCM). MYQORZO (aficamten) is a cardiac myosin inhibitor approved in the U.S., China and European Union for the treatment of symptomatic obstructive hypertrophic cardiomyopathy (oHCM). In patients with oHCM, myosin inhibition with MYQORZO reduces cardiac contractility and consequently, left ventricular outflow tract (LVOT) obstruction. MYQORZO was engineered to achieve a predictable exposure response, rapid onset of action and reversibility. Aficamten is also under clinical investigation in CEDAR-HCM, in a pediatric population with oHCM. Aficamten has not been deemed safe or effective for use in this patient population. In addition, aficamten is being studied in FOREST-HCM, an open-label extension clinical study. MYQORZO is indicated for the treatment of adults with symptomatic obstructive hypertrophic cardiomyopathy (oHCM) to improve functional capacity and symptoms. MYQORZO reduces left ventricular ejection fraction (LVEF) and can cause heart failure due to systolic dysfunction. Echocardiogram assessments are required prior to and during treatment with MYQORZO to monitor for systolic dysfunction. Initiation of MYQORZO in patients with LVEF. Because of the risk of heart failure due to systolic dysfunction, MYQORZO is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the MYQORZO REMS Program. MYQORZO is contraindicated with concomitant use of rifampin. MYQORZO reduces cardiac contractility, which can reduce LVEF and cause heart failure. Patients who experience a serious intercurrent illness (eg, serious infection) or arrhythmia (eg, new or uncontrolled atrial fibrillation) may be at greater risk of developing systolic dysfunction and heart failure. Assess patients’ clinical status and LVEF prior to and during treatment and adjust the MYQORZO dose accordingly. New or worsening arrhythmia, dyspnea, chest pain, fatigue, leg edema, or elevations in N-terminal pro-B-type natriuretic peptide may be signs and symptoms of heart failure. Initiation of MYQORZO in patients with LVEF. Patients must enroll in the MYQORZO REMS Program and comply with ongoing monitoring requirements. Pharmacies must be certified by enrolling in the MYQORZO REMS Program and must only dispense to patients who are authorized to receive MYQORZO. Wholesalers and distributors must only distribute to certified pharmacies. MYQORZO is metabolized primarily by CYP2C9, and to a lesser extent by CYP3A, CYP2D6, and CYP2C19 enzymes. Initiation of medications that inhibit multiple P450 pathways of MYQORZO elimination (eg, fluconazole, voriconazole, or fluvoxamine) or strong CYP2C9 inhibitors, and discontinuation of moderate-to-strong CYP3A inducers may lead to increased blood concentrations of aficamten and increase the risk of heart failure due to systolic dysfunction. Conversely, initiation of medications that induce P450 pathways of MYQORZO (eg, rifampin, moderate-to-strong CYP3A inducers) may lead to decreased blood concentrations of aficamten and potential loss of effectiveness. Assess LVEF 2 to 8 weeks after initiation of such inhibitors or after discontinuation of such inducers and adjust the dose of MYQORZO accordingly. Advise patients of the potential for drug interactions. Advise patients to inform their healthcare provider of all concomitant medications prior to and during MYQORZO treatment. Hypertension (8% vs 2%) was the only adverse reaction occurring in >5% of patients and more commonly on MYQORZO than on placebo in the pivotal trial. MYQORZO is indicated for the treatment of adults with symptomatic obstructive hypertrophic cardiomyopathy (oHCM) to improve functional capacity and symptoms. Hypertrophic cardiomyopathy (HCM) is a disease in which the heart muscle becomes abnormally thick. HCM can be obstructive, when thickened muscle blocks blood flow, or non-obstructive, when blood flow is not blocked but heart function is still affected. In obstructive HCM, the thickening of cardiac muscle leads to the inside of the left ventricle becoming smaller, stiffer and less able to relax and fill with blood. Ultimately, HCM limits the heart’s pumping function, leading to reduced exercise capacity and a variety of symptoms. HCM is the most common monogenic inherited cardiovascular disorder, with well over 300,000 patients diagnosed in the U.S. However, there are an estimated 400,000-800,000 additional patients who remain undiagnosed. Recent analysis of a large claims database indicates that approximately half of patients with HCM have obstructive HCM (oHCM) and half have non-obstructive HCM (nHCM). People with HCM are at high risk of also developing cardiovascular complications including atrial fibrillation, stroke and mitral valve disease. People with HCM are at risk for potentially fatal ventricular arrhythmias and it is one of the leading causes of sudden cardiac death in younger people or athletes. A subset of patients with HCM are at high risk of progressive disease leading to dilated cardiomyopathy and heart failure necessitating cardiac transplantation. There are no currently approved therapies for nHCM.
