细胞毒素在HCM协会科学会议上展示SEQUOIA-HCM的基线特征

Cytokinetics, Incorporated (NASDAQ:CYTK) today announced that the baseline characteristics of patients randomized in SEQUOIA-HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM), the pivotal Phase 3 clinical trial of aficamten in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM), were presented at the HCM Society Scientific Sessions in Cleveland, Ohio by Martin S. Maron, M.D., Director of the Hypertrophic Cardiomyopathy Center at Lahey Hospital and Medical Center.

 

"The baseline characteristics of SEQUOIA-HCM show that the patients enrolled into this pivotal trial align with our objectives for aficamten, which include assessing our next-in-class cardiac myosin inhibitor in a population with substantial deficit in exercise capacity and significant symptom burden despite background treatment with guideline directed medical therapies," said Fady I. Malik, M.D., Ph.D., Cytokinetics' Executive Vice President of Research & Development. "We look forward to announcing topline results from SEQUOIA-HCM by the end of the year and our hopefully elaborating on clinical effects to the benefit of patients."

SEQUOIA-HCM: Baseline Characteristics

SEQUOIA-HCM was designed to evaluate aficamten in patients with symptomatic obstructive HCM on background medical therapy over a 24-week period. Patients enrolled in SEQUOIA-HCM were required to have severe left ventricular outflow tract (LVOT) obstruction as evidenced by a resting LVOT-G ≥30 mmHg, a post-Valsalva peak LVOT-G ≥50 mmHg, NYHA functional class II or III, and a peak VO2 ≤90% predicted.

SEQUOIA-HCM enrolled a total of 282 patients, with one third from the United States, one half from Europe and Israel, and the remainder from China. Patients were on average 59.1 years of age, 40.4% female, and 21% were non-white. Background medical therapy consisted of beta-blockers (61%), calcium channel blockers (26.6%), and disopyramide (12.8%); combination background therapy was permitted. At baseline, 75.9% of patients were NYHA functional class II, 23.8% were functional class III, and 0.4% were functional class IV. One quarter of patients were guideline-eligible for septal reduction therapy at the time of enrollment. The pooled mean (SD) for baseline peak VO2 was 18.5 (4.5) mL/kg/min or 56.9% (11.8) of age- and sex-predicted peak VO2, and for the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) was 74.7 (18.0). The geometric mean (Q1, Q3) high-sensitivity cardiac troponin I was 12.1 (7.7, 27.3) ng/L. (Table 1). Key baseline characteristics that remain blinded include left ventricular ejection fraction (LVEF), resting and Valsalva LVOT-G, and NT-proBNP.

About Aficamten and the Broad Phase 3 Clinical Trials Program

Aficamten is an investigational selective, small molecule cardiac myosin inhibitor discovered following an extensive chemical optimization program that was conducted with careful attention to therapeutic index and pharmacokinetic properties and as may translate into next-in-class potential in clinical development. Aficamten was designed to reduce the number of active actin-myosin cross bridges during each cardiac cycle and consequently suppress the myocardial hypercontractility that is associated with hypertrophic cardiomyopathy (HCM). In preclinical models, aficamten reduced myocardial contractility by binding directly to cardiac myosin at a distinct and selective allosteric binding site, thereby preventing myosin from entering a force producing state.

The development program for aficamten is assessing its potential as a treatment that improves exercise capacity and relieves symptoms in patients with HCM as well as its potential long-term effects on cardiac structure and function. Aficamten is currently the subject of SEQUOIA-HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM), a pivotal Phase 3 clinical trial in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM), MAPLE-HCM (Metoprolol vs Aficamten in Patients with LVOT Obstruction on Exercise Capacity in HCM), a Phase 3 clinical trial evaluating aficamten as monotherapy compared to metoprolol as monotherapy in patients with obstructive HCM, and ACACIA-HCM (Assessment Comparing Aficamten to Placebo on Cardiac Endpoints In Adults with Non-Obstructive HCM), a pivotal Phase 3 clinical trial in patients with symptomatic non-obstructive HCM. Results from SEQUOIA-HCM are expected by the end of 2023. Aficamten received Breakthrough Therapy Designation for the treatment of symptomatic obstructive HCM from the U.S. Food & Drug Administration (FDA) as well as the National Medical Products Administration (NMPA) in China.

About Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is a disease in which the heart muscle (myocardium) becomes abnormally thick (hypertrophied). The thickening of cardiac muscle leads to the inside of the left ventricle becoming smaller and stiffer, and thus the ventricle becomes less able to relax and fill with blood. This ultimately limits the heart's pumping function, resulting in reduced exercise capacity and symptoms including chest pain, dizziness, shortness of breath, or fainting during physical activity. HCM is the most common monogenic inherited cardiovascular disorder, with approximately 280,000 patients diagnosed in the U.S., however, there are an estimated 400,000-800,000 additional patients who remain undiagnosed.1,2,3 Two-thirds of patients with HCM have obstructive HCM (oHCM), where the thickening of the cardiac muscle leads to left ventricular outflow tract (LVOT) obstruction, while one-third have non-obstructive HCM (nHCM), where blood flow isn't impacted, but the heart muscle is still thickened. People with HCM are at high risk of also developing cardiovascular complications including atrial fibrillation, stroke and mitral valve disease.4 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.5 A subset of patients with HCM are at high risk of progressive disease leading to dilated cardiomyopathy and heart failure necessitating cardiac transplantation.