SOUTH SAN FRANCISCO, Calif., May 08, 2024 (GLOBE NEWSWIRE) -- Cytokinetics, Incorporated (Nasdaq: CYTK) today announced that CEDAR-HCM (Clinical Evaluation of Dosing with Aficamten to Reduce Obstruction in a Pediatric Population in HCM), a clinical trial of aficamten in a pediatric population with symptomatic obstructive hypertrophic cardiomyopathy (HCM), is open to enrollment.

加利福尼亚州南旧金山，2024年5月8日（环球通讯社）--Cytokinetics，Incorporated（Nasdaq:CYTK）今天宣布，CEDAR-HCM（临床评估服用Aficamten以减少HCM儿科人群的阻塞）是一项针对有症状阻塞性肥厚型心肌病（HCM）儿科人群的Aficamten临床试验，可供登记。

Aficamten is a next-in-class cardiac myosin inhibitor in development for the potential treatment of HCM..

Aficamten是正在开发的下一类心肌肌球蛋白抑制剂，用于潜在的HCM治疗。。

“We are pleased to further expand the broad development program for aficamten with the start of CEDAR-HCM, a trial assessing the safety and efficacy of a cardiac myosin inhibitor in a pediatric population,” said Fady I. Malik, M.D., Ph.D., Cytokinetics’ Executive Vice President of Research & Development.

细胞动力学研究与开发执行副总裁Fady I.Malik博士说：“我们很高兴随着CEDAR-HCM的启动，进一步扩大了aficamten的广泛开发计划，该试验评估了心肌肌球蛋白抑制剂在儿科人群中的安全性和有效性。”。

“As a genetic disease, HCM often casts a shadow over entire families, including adolescents and children where it is associated with a high risk of heart failure and serious arrhythmias. HCM can present similarly in adolescents and children as it does in adults and may negatively impact overall quality of life.

“作为一种遗传性疾病，HCM经常给整个家庭带来阴影，包括青少年和儿童，因为它与心力衰竭和严重心律不齐的高风险有关。HCM在青少年和儿童中的表现与成人相似，可能会对整体生活质量产生负面影响。

By evaluating the efficacy and safety of aficamten in another very important group of people, our aim is to provide all members of families impacted by HCM with a potential new treatment option.”.

通过评估aficamten在另一个非常重要的人群中的疗效和安全性，我们的目标是为受HCM影响的所有家庭成员提供潜在的新治疗选择。”。

CEDAR-HCM: Clinical Trial Design

CEDAR-HCM：临床试验设计

CEDAR-HCM is a multi-center, randomized, double-blind, placebo-controlled and open-label extension clinical trial to evaluate the efficacy, pharmacokinetics (PK) and safety of aficamten in a pediatric population with symptomatic obstructive HCM. The primary endpoint is the change in Valsalva left ventricular outflow tract gradient (LVOT-G) from baseline to Week 12.

CEDAR-HCM是一项多中心，随机，双盲，安慰剂对照和开放标签的扩展临床试验，旨在评估阿非卡姆在有症状阻塞性HCM的儿科人群中的疗效，药代动力学（PK）和安全性。主要终点是Valsalva左心室流出道梯度（LVOT-G）从基线到第12周的变化。

Secondary endpoints include the change from baseline to Week 12 in resting LVOT-G, New York Heart Association (NYHA) Functional Class, pharmacokinetics and cardiac biomarkers including NT-proBNP and hs-cTnI..

次要终点包括静息LVOT-G，纽约心脏协会（NYHA）功能分级，药代动力学和心脏生物标志物（包括NT-proBNP和hs-cTnI）从基线到第12周的变化。。

CEDAR-HCM is expected to enroll two cohorts, beginning with an initial cohort of approximately 40 adolescent patients aged 12 to 17. Adolescent patients enrolled in CEDAR-HCM must have LVEF ≥ 60%, Valsalva LVOT-G ≥ 50 mmHg and NYHA Functional Class ≥ II. Patients will be randomized on a 2:1 basis to receive aficamten or placebo, and those receiving aficamten will begin with 5 mg dosed once daily.

CEDAR-HCM预计将招募两个队列，首先是大约40名12至17岁的青少年患者。参加CEDAR-HCM的青少年患者必须具有LVEF≥60%，Valsalva LVOT-G≥50 mmHg和NYHA功能分级≥II级。患者将以2:1的比例随机接受阿非卡姆汀或安慰剂治疗，接受阿非卡姆汀治疗的患者将从每天一次服用5毫克开始。

At weeks 2, 4 and 6 patients will receive an echocardiogram to determine if they will be up-titrated to escalating doses of 10, 15 or 20 mg. Dose escalation will occur only if a patient has a Valsalva LVOT-G ≥ 30 mmHg and an LVEF ≥ 55%. Safety, efficacy and PK data obtained from at least 20 adolescent patients who have completed 12 weeks of double-blind treatment will support the decision to open enrollment in a second cohort of approximately 8 to 10 younger patients (aged 6 to 11).

在第2周、第4周和第6周，患者将接受超声心动图检查，以确定他们是否会被滴定到10、15或20 mg的递增剂量。只有当患者的Valsalva LVOT-G≥30 mmHg且LVEF≥55%时，才会发生剂量递增。从至少20名完成12周双盲治疗的青少年患者获得的安全性，有效性和PK数据将支持决定在第二组约8至10名年轻患者（6至11岁）中开放登记。

The protocol will be amended to include eligibility criteria and dose selection for the younger pediatric cohort. After 12 weeks of double-blind treatment, eligible patients will rollover into the open label extension period of CEDAR-HCM. Additional information can be found on www.clinicaltrials.gov..

该方案将进行修订，以包括年轻儿科队列的资格标准和剂量选择。经过12周的双盲治疗后，符合条件的患者将进入CEDAR-HCM的开放标签延长期。更多信息可以在www.clinicaltrials.gov上找到。。

About Aficamten

关于Aficamten

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是一种研究性选择性小分子心肌肌球蛋白抑制剂，是在广泛的化学优化程序后发现的，该程序仔细关注治疗指数和药代动力学特性，并可能转化为临床开发中的下一个同类潜力。

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..

Aficamten旨在减少每个心动周期中活跃的肌动蛋白-肌球蛋白跨桥的数量，从而抑制与肥厚型心肌病（HCM）相关的心肌过度收缩。在临床前模型中，aficamten通过在独特且选择性的变构结合位点直接与心肌肌球蛋白结合来降低心肌收缩力，从而防止肌球蛋白进入产生力的状态。。

About the Broad Phase 3 Clinical Trials Program for Aficamten

关于Aficamten的广泛3期临床试验计划

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的开发计划正在评估其作为改善HCM患者运动能力和缓解症状的治疗潜力，以及其对心脏结构和功能的潜在长期影响。

SEQUOIA-HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM), was the pivotal Phase 3 clinical trial in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM). The results from SEQUOIA-HCM show that treatment with aficamten significantly improved exercise capacity compared to placebo, increasing peak oxygen uptake (pVO2) measured by cardiopulmonary exercise testing (CPET) by a least square mean difference (95% CI) of 1.74 (1.04 - 2.44) mL/kg/min (p=0.000002).

SEQUOIA-HCM（Aficamten在HCM中的阻塞影响的安全性，有效性和定量理解）是症状性梗阻性肥厚型心肌病（HCM）患者的关键3期临床试验。SEQUOIA-HCM的结果显示，与安慰剂相比，阿非卡姆汀治疗显着提高了运动能力，通过心肺运动试验（CPET）测量的峰值摄氧量（pVO2）增加了1.74（1.04-2.44）mL/kg/min的最小二乘平均差（95%CI）（p=0.000002）。

The treatment effect with aficamten was consistent across all prespecified subgroups reflective of patient baseline characteristics and treatment strategies, including patients receiving or not receiving background beta-blocker therapy. Statistically significant (p<0.0001) and clinically meaningful improvements were also observed in all 10 prespecified secondary endpoints.

在反映患者基线特征和治疗策略的所有预先指定的亚组（包括接受或不接受背景β受体阻滞剂治疗的患者）中，阿非卡姆汀的治疗效果是一致的。在所有10个预先指定的次要终点中，也观察到统计学上显着（p<0.0001）和临床上有意义的改善。

Aficamten was well-tolerated with an adverse event profile comparable to placebo. Treatment emergent serious adverse events occurred in 8 (5.6%) and 13 (9.3%) patients on aficamten and placebo, respectively. Core echocardiographic left ventricular ejection fraction (LVEF) was observed to be <50% in 5 patients (3.5%) on aficamten compared to 1 patient (0.7%) on placebo.

Aficamten耐受性良好，不良事件概况与安慰剂相当。阿非卡姆汀组和安慰剂组分别有8例（5.6%）和13例（9.3%）患者出现治疗紧急严重不良事件。核心超声心动图左心室射血分数（LVEF）在5例患者（3.5%）中观察到小于50%，而安慰剂组为1例（0.7%）。

There were no instances of worsening heart failure or treatment interruptions due to low LVEF..

没有因LVEF低而导致心力衰竭恶化或治疗中断的情况。。

Aficamten is also currently being evaluated in MAPLE-HCM, a Phase 3 clinical trial of aficamten as monotherapy compared to metoprolol as monotherapy in patients with obstructive HCM, ACACIA-HCM, a Phase 3 clinical trial of aficamten in patients with non-obstructive HCM, CEDAR-HCM, a clinical trial of aficamten in a pediatric population with obstructive HCM, and FOREST-HCM, an open label extension clinical study of aficamten in patients with hypertrophic cardiomyopathy (HCM).

Aficamten目前也正在MAPLE-HCM中进行评估，MAPLE-HCM是Aficamten作为单一疗法的3期临床试验，而美托洛尔作为阻塞性HCM患者的单一疗法，ACACIA-HCM是Aficamten在非阻塞性HCM患者中的3期临床试验，CEDAR-HCM是Aficamten在阻塞性HCM儿科人群中的临床试验，FOREST-HCM是Aficamten在肥厚型心肌病（HCM）患者中的开放标签扩展临床研究。

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..

Aficamten获得了美国食品和药物管理局（FDA）以及中国国家医疗产品管理局（NMPA）的突破性治疗指定，用于治疗症状性阻塞性HCM。。

About Hypertrophic Cardiomyopathy

关于肥厚型心肌病

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.

肥厚型心肌病（HCM）是一种心肌（心肌）异常增厚（肥大）的疾病。心肌增厚导致左心室内部变得更小和更硬，因此心室变得不太能够放松和充满血液。

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.

这最终限制了心脏的泵送功能，导致运动能力下降和症状，包括胸痛，头晕，呼吸急促或在体育活动中晕倒。HCM是最常见的单基因遗传性心血管疾病，在美国诊断出约280000名患者，然而，估计还有400000-800000名患者仍未确诊。1,2,3三分之二的HCM患者患有阻塞性HCM（oHCM），心肌增厚导致左心室流出道（LVOT）阻塞，而三分之一的患者患有非阻塞性HCM（nHCM），血流不受影响，但心肌仍增厚。

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..

HCM患者也有发生心血管并发症的高风险，包括心房颤动，中风和二尖瓣疾病。4 HCM患者有潜在致命性室性心律失常的风险，是年轻人或运动员心源性猝死的主要原因之一。5一部分HCM患者患进行性疾病的风险很高，导致扩张型心肌病和心力衰竭，需要进行心脏移植。。

About Cytokinetics

关于细胞动力学

Cytokinetics is a late-stage, specialty cardiovascular biopharmaceutical company focused on discovering, developing and commercializing first-in-class muscle activators and next-in-class muscle inhibitors as potential treatments for debilitating diseases in which cardiac muscle performance is compromised.

细胞动力学是一家晚期专业心血管生物制药公司，专注于发现，开发和商业化一流的肌肉激活剂和一流的肌肉抑制剂，作为心肌功能受损的衰弱性疾病的潜在治疗方法。

As a leader in muscle biology and the mechanics of muscle performance, the company is developing small molecule drug candidates specifically engineered to impact myocardial muscle function and contractility. Cytokinetics is preparing for regulatory submissions for aficamten, its next-in-class cardiac myosin inhibitor, following positive results from SEQUOIA-HCM, the pivotal Phase 3 clinical trial in obstructive hypertrophic cardiomyopathy.

作为肌肉生物学和肌肉性能力学的领导者，该公司正在开发专门用于影响心肌功能和收缩力的小分子候选药物。继SEQUOIA-HCM（梗阻性肥厚型心肌病的关键3期临床试验）的阳性结果之后，细胞动力学正在为其下一类心肌肌球蛋白抑制剂aficamten的监管提交准备。

Aficamten is also currently being evaluated in MAPLE-HCM, a Phase 3 clinical trial of aficamten as monotherapy compared to metoprolol as monotherapy in patients with obstructive HCM, ACACIA-HCM, a Phase 3 clinical trial of aficamten in patients with non-obstructive HCM, CEDAR-HCM, a clinical trial of aficamten in a pediatric population with obstructive HCM, and FOREST-HCM, an open label extension clinical study of aficamten in patients with hypertrophic cardiomyopathy (HCM).

Aficamten目前也正在MAPLE-HCM中进行评估，MAPLE-HCM是Aficamten作为单一疗法的3期临床试验，而美托洛尔作为阻塞性HCM患者的单一疗法，ACACIA-HCM是Aficamten在非阻塞性HCM患者中的3期临床试验，CEDAR-HCM是Aficamten在阻塞性HCM儿科人群中的临床试验，FOREST-HCM是Aficamten在肥厚型心肌病（HCM）患者中的开放标签扩展临床研究。

Cytokinetics is also developing omecamtiv mecarbil, a cardiac muscle activator, in patients with heart failure. Additionally, Cytokinetics is developing CK-586, a cardiac myosin inhibitor with a mechanism of action distinct from aficamten for the potential treatment of HFpEF, and CK-136, a cardiac troponin activator for the potential treatment HFrEF and other types of heart failure, such as right ventricular failure resulting from impaired cardiac contractility..

细胞动力学也在心力衰竭患者中开发心肌激活剂omecamtiv-mecarbil。此外，细胞动力学正在开发CK-586，一种心肌肌球蛋白抑制剂，其作用机制不同于用于潜在治疗HFpEF的aficamten，以及CK-136，一种用于潜在治疗HFrEF和其他类型心力衰竭的心肌肌钙蛋白激活剂，如因心脏收缩力受损导致的右心室衰竭。。