Cytokinetics, Incorporated announced that additional data from SEQUOIA-HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM), the pivotal Phase III clinical trial of aficamten in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM), related to cardiac remodeling and improvements in patient symptoms, cardiac structure, function and biomarkers, were presented in three Late Breaking Clinical Trial presentations and one oral presentation at the European Society of Cardiology Congress 2024 in London, UK.

Cytokinetics，Incorporated宣布，SEQUOIA-HCM（Aficamten在HCM中的阻塞影响的安全性，有效性和定量理解）的其他数据，这是Aficamten在症状性梗阻性肥厚型心肌病（HCM）患者中的关键III期临床试验，与心脏重塑和患者症状，心脏结构，功能和生物标志物的改善有关，在英国伦敦2024年欧洲心脏病学会大会的三次晚期临床试验报告和一次口头报告中进行了介绍。

These presentations were accompanied by simultaneous publications in leading cardiac journals, three in the Journal of the American College of Cardiology and one in the European Heart Journal.

这些演讲同时在主要的心脏杂志上发表，其中三篇发表在美国心脏病学会杂志上，另一篇发表在欧洲心脏杂志上。

“As we continue to dissect data from SEQUOIA-HCM, the expanding body of evidence reinforces the effects of aficamten on clinical outcomes, symptom burden, cardiac biomarkers and cardiac structure and function,” said Stephen Heitner, M.D., Vice President, Head of Clinical Research. “Key data presented and published show that treatment with aficamten appears to improve the architecture of the heart in patients with obstructive HCM, suggesting potential for disease modification.

临床研究负责人、副总裁斯蒂芬·海特纳（StephenHeitner）医学博士说：“随着我们继续分析红杉-HCM的数据，越来越多的证据加强了阿非卡姆汀对临床结果、症状负担、心脏生物标志物以及心脏结构和功能的影响。”。“提供和公布的关键数据表明，使用非依卡姆汀治疗似乎可以改善阻塞性HCM患者的心脏结构，提示疾病改变的潜力。

These data reinforce the primary analyses of SEQUOIA-HCM which are central to our rolling NDA submission for aficamten expected to be completed during this third quarter.”.

这些数据加强了红杉-HCM的主要分析，这是我们为aficamten提交的滚动NDA的核心，预计将在第三季度完成。”。

Data from SEQUOIA-HCM CMR Sub-Study Show Treatment with Aficamten is Associated with Favorable Cardiac Remodeling: Ahmad Masri, M.D., MS, Director of the Hypertrophic Cardiomyopathy Center at Oregon Health & Science University presented data from the cardiac magnetic resonance (CMR) sub-study in SEQUOIA-HCM.

来自SEQUOIA-HCM CMR子研究的数据显示，使用Aficamten治疗与良好的心脏重塑有关：俄勒冈州健康与科学大学肥厚型心肌病中心主任Ahmad Masri，医学博士，MS提供了来自SEQUOIA-HCM心脏磁共振（CMR）子研究的数据。

The data were simultaneously published in Journal of the American College of Cardiology. Of the 282 patients with obstructive HCM who participated in SEQUOIA-HCM, 57 patients participated in the CMR-sub-study and 50 patients completed the study, including 21 patients who received aficamten and 29 patients who received placebo.

这些数据同时发表在《美国心脏病学会杂志》上。在参加SEQUOIA-HCM的282名阻塞性HCM患者中，57名患者参加了CMR子研究，50名患者完成了研究，包括21名接受阿非卡姆汀治疗的患者和29名接受安慰剂治疗的患者。

Baseline characteristics of patients enrolled in the CMR sub-study were comparable to the overall patient population in SEQUOIA-HCM..

参加CMR子研究的患者的基线特征与SEQUOIA-HCM的总体患者人群相当。。

The primary endpoint in the CMR sub-study was the change from baseline to Week 24 in left ventricular mass index (LVMI) from baseline. Treatment with aficamten significantly improved LVMI (-15.4 g/m2, p=0.001) and resulted in favorable cardiac remodeling as demonstrated by reductions 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),' while replacement fibrosis (late gadolinium enhancement [lge]) remained stable.

CMR子研究的主要终点是左心室质量指数（LVMI）从基线到第24周的变化。阿非卡姆汀治疗可显着改善LVMI（-15.4 g/m2，p=0.001），并导致良好的心脏重塑，如左心室最大壁厚（p<0.001），左心房容积指数（lavi）（p><0.001）和细胞外容积质量指数（ecvi）（p='0.014），而替代性纤维化（晚期钆增强[lge]）保持稳定。

these observed structural changes are suggestive of ongoing favorable remodeling and occurred in conjunction with improvements in clinical endpoints including resting and valsalva left ventricular outflow tract gradient (lvot-g), nt-probnp and nyha functional class. a cmr sub-study is also being conducted in forest-hcm, the ongoing open-label extension clinical trial of aficamten, to evaluate cardiac remodeling associated with long-term treatment with aficamten, as well as in acacia-hcm, the pivotal phase iii clinical trial of aficamten in patients with non-obstructive hcm..

这些观察到的结构变化提示正在进行有利的重塑，并与临床终点的改善相结合，包括静息和valsalva左心室流出道梯度（lvot-g），nt-probnp和nyha功能分级。正在进行的aficamten开放标签扩展临床试验forest hcm也正在进行cmr子研究，以评估与aficamten长期治疗相关的心脏重塑，以及acacia hcm，aficamten在非阻塞性hcm患者中的关键iii期临床试验。。

Aficamten Improves Echocardiographic Measures of Cardiac Structure and Function Without Negatively Impacting Systolic Function: Sheila Hegde, M.D., M.P.H., Cardiovascular Medicine Specialist, Division of Cardiovascular Medicine, Brigham and Women’s Hospital presented data from an analysis of the impact of treatment with aficamten on echocardiographic cardiac structure and function from SEQUOIA-HCM.

Aficamten改善了心脏结构和功能的超声心动图测量，而不会对收缩功能产生负面影响：Brigham and Women's Hospital心血管医学科心血管医学专家Sheila Hegde，M.D.，M.P.H。提供了来自SEQUOIA-HCM的Aficamten治疗对超声心动图心脏结构和功能影响分析的数据。

The data were simultaneously published in Journal of the American College of Cardiology. As previously reported, treatment with aficamten significantly improved gradients by approximately 60%, improving placebo-corrected resting LVOT-G -40 mmHg (55 to 20 mmHg with aficamten) and Valsalva LVOT-G -50 mmHg (86 to 35 mmHg with aficamten) , with no significant adverse changes in left ventricular systolic function, as measured by left ventricular ejection fraction (LVEF) (-4.8%, 95% CI -6.4 to -3.3; p<0.001).

这些数据同时发表在《美国心脏病学会杂志》上。如先前报道，用阿非卡姆汀治疗可显着改善梯度约60%，改善安慰剂校正的静息LVOT-G-40 mmHg（阿非卡姆汀55-20 mmHg）和Valsalva LVOT-G-50 mmHg（阿非卡姆汀86-35 mmHg），左心室射血分数（LVEF）（-4.8%，95%CI-6.4-3.3；p＜0.001）测量左心室收缩功能无明显不良变化。

aficamten also improved measures of left ventricular structure and function including maximal wall thickness, septal wall thickness, inferolateral wall thickness, left ventricular mass index, and left ventricular end systolic volume index, with no change in left ventricular end diastolic volume index.

aficamten还改善了左心室结构和功能的测量，包括最大壁厚，间隔壁厚，下外侧壁厚，左心室质量指数和左心室收缩末期容积指数，而左心室舒张末期容积指数没有变化。

aficamten also improved lavi as well as left ventricular relaxation and filling as indicated by an increase in lateral e’ velocity and decrease in lateral e e’, findings consistent with an improvement in diastolic function . The improvements in these echocardiographic measures were each associated with improvements in pVO2, Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) and NT-proBNP, demonstrating that the effects of aficamten on cardiac function and structure were associated with improvements in exercise capacity, symptoms and quality of life..

aficamten还改善了lavi以及左心室舒张和充盈，如横向e'速度的增加和横向e e的减少所示，发现与舒张功能的改善一致。这些超声心动图测量的改善均与pVO2，堪萨斯城心肌病问卷临床总结评分（KCCQ-CSS）和NT-proBNP的改善有关，表明阿非卡姆汀对心脏功能和结构的影响与运动能力，症状和生活质量的改善有关。。

Aficamten Improves Symptom Burden and Quality of Life in Patients with Obstructive HCM: John A. Spertus, M.D., M.P.H., Professor, Daniel J. Lauer Missouri Endowed Chair in Metabolic and Vascular Disease Research, Clinical Director, University of Missouri Kansas City Healthcare Institute for Innovations in Quality and Saint Luke’s Mid America Heart Institute presented results from an analysis of the effect of treatment with aficamten on patient symptom burden, including the Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS) and the Seattle Angina Questionnaire Summary Score (SAQ-SS) from SEQUOIA-HCM.

Aficamten改善阻塞性HCM患者的症状负担和生活质量：John A.Spertus，M.D.，M.P.H.，教授，Daniel J.Lauer Missouri Endered代谢和血管疾病研究主席，密苏里大学堪萨斯城医疗保健质量创新研究所和圣卢克中美心脏研究所临床主任介绍了Aficamten治疗对患者症状负担影响的分析结果，包括堪萨斯城心肌病问卷总分（KCCQ-OSS）和SEQUOIA-HCM的西雅图心绞痛问卷总分（SAQ-SS）。

The data were simultaneously published in Journal of the American College of Cardiology. At 24 weeks, aficamten significantly improved KCCQ-OSS by 7.9 points (95% CI 4.8 to 11; p<0.001). very large improvements in kccq-oss ( greater than 20 points) were achieved by 30% of patients treated with aficamten compared to 12% of patients treated with placebo (number needed to treat (nnt)='5.8).' similarly, aficamten significantly improved saq-ss scores by 7.8 points (95% ci 4.7 to 11; p><0.001), with 31% of patients treated with aficamten experiencing a very large improvement ( greater than 20 points) compared to 14% of patients on placebo (nnt='5.8).' no significant heterogeneity was observed in improvements in kccq-oss and saq-ss according to patient baseline characteristics, including the severity of disease or level of symptom burden.

这些数据同时发表在《美国心脏病学会杂志》上。在24周时，阿非卡姆汀显着改善KCCQ-OSS 7.9分（95%CI 4.8-11；p＜0.001）。与安慰剂治疗的12%患者（需要治疗的人数（nnt）='5.8）相比，30%接受阿非卡姆汀治疗的患者在kccq oss方面取得了非常大的改善（大于20分）。'同样，阿非卡姆汀显着改善了saq ss评分7.8分（95%可信区间为4.7至11；p><0.001），31%接受阿非卡姆汀治疗的患者有非常大的改善（大于20分），而安慰剂组为14%（nnt='5.8）。'根据患者的基线特征，包括疾病的严重程度或症状负担水平，在kccq oss和saq ss的改善方面没有观察到显着的异质性。

even in patients with minimal angina at baseline, saq-ss scores improved after 24 weeks of treatment with aficamten. These results indicate that treatment with aficamten significantly improves patient health status including symptoms, function and quality of life. .

即使在基线时有轻微心绞痛的患者中，用阿非卡姆汀治疗24周后，saq ss评分也有所改善。这些结果表明，使用阿非卡姆汀治疗可显着改善患者的健康状况，包括症状，功能和生活质量。

Aficamten Improves Cardiac Biomarkers Including NT-proBNP and hs-cTnI: Caroline Coats, M.D., Ph.D., Lead Clinician, West of Scotland Inherited Cardiac Conditions Service, Honorary Senior Lecturer, School of Cardiovascular and Metabolic Health, University of Glasgow presented results from a pre-specified secondary analysis from SEQUOIA-HCM related to NT-proBNP and high sensitivity cardiac troponin (hs-cTnI), cardiac biomarkers indicative of cardiac wall stress and myocardial injury.

Aficamten改善了包括NT-proBNP和hs-cTnI在内的心脏生物标志物：卡罗琳·科茨（Caroline Coats），医学博士，博士，首席临床医生，苏格兰西部遗传心脏病服务中心，格拉斯哥大学心血管与代谢健康学院名誉高级讲师，介绍了红杉-HCM与NT-proBNP和高敏心肌肌钙蛋白（hs-cTnI）相关的预先指定的二次分析结果，表明心脏壁压力和心肌损伤的心脏生物标志物。

The results were simultaneously published in the European Heart Journal. Higher baseline concentrations of NT-proBNP and hs-cTnI were associated with worse baseline echocardiographic measures of disease severity including resting and Valsalva LVOT-G, LVEF and left ventricular wall thickness. Treatment with aficamten for 24 weeks resulted in an 80% reduction in NT-proBNP (p<0.001) and a 43% reduction (p><0.001) in hs-ctni .

研究结果同时发表在《欧洲心脏杂志》上。较高的NT-proBNP和hs-cTnI基线浓度与较差的疾病严重程度基线超声心动图测量相关，包括静息和Valsalva LVOT-G，LVEF和左心室壁厚。阿非卡姆汀治疗24周后，NT-proBNP降低80%（p＜0.001），hs-ctni降低43%（p＜0.001）。

both measurements returned to baseline after washout. baseline measurements of nt-probnp and hs-ctni were not correlated with change in pvo2 such that treatment with aficamten significantly improved pvo2 irrespective of baseline biomarkers. baseline nt-probnp and hs-ctni also did not predict future instances of lvef><50%.

冲洗后，两次测量均恢复到基线。nt-probnp和hs-ctni的基线测量值与pvo2的变化无关，因此无论基线生物标志物如何，用aficamten治疗均显着改善pvo2。基线nt-probnp和hs-ctni也不能预测未来lvef>50%的情况。

however, at 24 weeks, improvements in nt-probnp and hs-ctni were strongly associated with improvements in lvot-g, pvo2 and kccq. improvements in nt-probnp were shown to closely mirror improvements in pvo2, which was not directly related to the reduction in lvot-g, indicating that nt-probnp may serve as an independent surrogate for change in pvo2.

然而，在24周时，nt-probnp和hs-ctni的改善与lvot-g，pvo2和kccq的改善密切相关。nt-probnp的改善与pvo2的改善密切相关，pvo2的改善与lvot-g的减少没有直接关系，这表明nt-probnp可以作为pvo2变化的独立替代指标。

additionally, changes in nt-probnp as early as week 2 were strongly associated with changes in valsalva lvot-g, kccq-css, lavi and lateral e e’ at week 24, indicating that early improvements in nt-probnp may be a .

此外，早在第2周，nt-probnp的变化与第24周valsalva lvot-g，kccq css，lavi和侧向e'的变化密切相关，表明nt-probnp的早期改善可能是一种。

See- Masri A, et al. 'Effect of Aficamten on Cardiac Structure and Function in Obstructive Hypertrophic Cardiomyopathy: SEQUOIA-HCM CMR Substudy'. JACC. 2024.

参见Masri A等人的《阿非卡姆汀对梗阻性肥厚型心肌病心脏结构和功能的影响：红杉-HCM CMR亚研究》。JACC公司。2024

See-Hegde S, et al. 'Impact of Aficamten on Echocardiographic Cardiac Structure and Function in Symptomatic Obstructive Hypertrophic Cardiomyopathy'. JACC. 2024.

参见Hegde S等人的“Aficamten对症状性梗阻性肥厚型心肌病超声心动图心脏结构和功能的影响”。JACC公司。2024

See- Sherrod C, et al. 'Effect of Aficamten on Health Status Outcomes in Obstructive Hypertrophic Cardiomyopathy: Results from SEQUOIA-HCM '. JACC. 2024.

参见Sherrod C等人的《阿非卡姆汀对梗阻性肥厚型心肌病健康状况结果的影响：红杉-HCM的结果》。JACC公司。2024

See-Coats CJ, et al.' Cardiac Biomarkers and Effects of Aficamten in Obstructive Hypertrophic Cardiomyopathy: The SEQUOIA-HCM Trial'. Eur Heart J. 2024.

参见Coats CJ等人的《梗阻性肥厚型心肌病中的心脏生物标志物和Aficamten的作用：红杉-HCM试验》。《欧洲心脏杂志》，2024年。

Condition: Hypertrophic Cardiomyopathy

条件：肥厚型心肌病

Type: drug

类型：药物