An Open-Label Extension Study to Evaluate the Long-Term Effects of ACE-083 in Patients with Facioscapulohumeral Muscular Dystrophy (FSHD) Previously Enrolled in Study A083-02 and in Patients with Charcot-Marie Tooth (CMT) Disease Types 1 and X Previously Enrolled in Study A083-03

开始日期2019-05-14

申办/合作机构

Acceleron Pharma, Inc.

NCT03943290

/ Terminated临床2期

An Open-Label Extension Study to Evaluate the Long-Term Effects of ACE-083 in Patients With Facioscapulohumeral Muscular Dystrophy (FSHD) Previously Enrolled in Study A083-02 and in Patients With Charcot-Marie Tooth (CMT) Disease Types 1 and X Previously Enrolled in Study A083-03

This is an open-label, multicenter, phase 2 extension study to evaluate the safety, tolerability, PK, PD, and efficacy of ACE-083 in subjects with FSHD previously enrolled in Study A083-02 and subjects with CMT1 and CMTX previously enrolled in Study A083-03. This study will be conducted in two Parts: Part 1, which is a loading phase of 6 months' duration, and Part 2, the maintenance phase, which will last up to 24 months.

开始日期2019-05-10

申办/合作机构

Acceleron Pharma, Inc.

NCT03124459

/ Terminated临床2期

A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of ACE-083 in Patients With Charcot-Marie-Tooth Disease Types 1 and X

This is a multicenter, phase 2 study to evaluate the safety, tolerability, pharmacodynamics (PD), efficacy, and pharmacokinetics (PK) of ACE-083 in patients with Charcot-Marie-Tooth Disease Type 1 and Type X (CMT1 and CMTX), to be conducted in two parts. Part 1 is non-randomized, open-label, dose-escalation and Part 2 is randomized, double-blind, and placebo-controlled.

开始日期2017-07-31

申办/合作机构

Acceleron Pharma, Inc.

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100 项与 Efmitermant alfa 相关的专利（医药）

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项与 Efmitermant alfa 相关的文献（医药）

2022-06-07·Neurology

Randomized Phase 2 Study of ACE-083 in Patients With Charcot-Marie-Tooth Disease

Article

作者: Pestronk, Alan ; Brannagan, Thomas H ; Subramony, Sub H ; van de Rijn, Marc ; Miller, Barry ; Karam, Chafic ; Johnson, Nicholas E ; Stevens-Favorite, Katherine ; Eichinger, Katy J ; Fowler, Marcie ; Thomas, Florian P ; Walk, David ; Attie, Kenneth M ; Statland, Jeffrey M ; Desai, Urvi ; Herrmann, David N ; Shy, Michael E ; Quinn, Colin ; Leneus, Ashley ; Habib, Ali A ; Butterfield, Russell J

Background and Objectives:

The goal of this work was to determine whether locally acting ACE-083 is safe and well tolerated and increases muscle volume, motor function, and quality of life (QoL) in adults with Charcot-Marie-Tooth disease (CMT) type 1.

Methods:

This phase 2 study enrolled adults with CMT1 or CMTX (N = 63). Part 1 was open label and evaluated the safety and tolerability of different dose levels of ACE-083 for use in part 2. Part 2 was a randomized, placebo-controlled, 6-month study of 240 mg/muscle ACE-083 injected bilaterally into the tibialis anterior muscle, followed by a 6-month, open-label extension in which all patients received ACE-083. Pharmacodynamic endpoints included total muscle volume (TMV; primary endpoint), contractile muscle volume (CMV), and fat fraction. Additional secondary endpoints included 6-minute walk test, 10-m walk/run, muscle strength, and QoL. Safety was assessed with treatment-emergent adverse events (TEAEs) and clinical laboratory tests.

Results:

In part 1 (n = 18), ACE-083 was generally safe and well tolerated at all dose levels, with no serious adverse events, TEAEs of grade 3 or greater, or death reported. In part 2 (n = 45 enrolled, n = 44 treated), there was significantly greater change in TMV with ACE-083 compared with placebo (least-squares mean difference 13.5%; p = 0.0096). There was significant difference between ACE-083 and placebo for CMV and change in ankle dorsiflexion strength. Fat fraction and all other functional outcomes were not significantly improved by ACE-083. Moderate to mild injection-site reactions were the most common TEAEs.

Discussion:

Despite significantly increased TMV and CMV, patients with CMT receiving ACE-083 in tibialis anterior muscles did not demonstrate greater functional improvement compared with those receiving placebo.

Trial Registration Information:

Clinical Trials Registration: NCT03124459.

Classification of Evidence:

This study provides Class II evidence that intramuscular ACE-083 is safe and well tolerated and increases total muscle volume after 6 months of treatment in adults with CMT1 or CMTX.

2020-05-10·Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics

[Research advance of underlying pathogenesis and target therapies in Charcot-Marie-Tooth disease type 1A].

Review

作者: Zhang, Ruxu ; Cao, Wanqian

Charcot-Marie-Tooth disease (CMT) is the commonest form of inherited neuropathy and has an incidence of 1/2500. CMT1A is the commonest subtype of CMT, which is caused by duplication of peripheral myelin protein 22 (PMP22) gene and accounts for approximately 50% of CMT diagnosed by genetic testing. Duplication of PMP22 may influence the production of PMP22 mRNA and protein, and interfere with the proliferation, differentiation and apoptosis of Schwann cells. In addition, deregulation of NRG1/ErbB pathway and lipid metabolism can also lead to dysfunction of Schwann cells. Such factors may disturb the myelination process, leading to axon degeneration, muscle weakness, and atrophy subsequently. Accordingly, drug therapies for CMT1A are developed by targeting such factors. PXT3003, antisense oligonucleotides (ASOs) and small interfering RNA (siRNA) are supposed to down-regulate the level of PMP22 mRNA, while recombinant human NRG-1 (rhNRG1) and neurotrophin-3 (NT-3) may enhance Schwann cells survival and differentiation. In addition, lipid-supplemented diet may remedy the defect of lipid metabolism and maintain the proper structure of myelin. Other targeting drugs include ascorbic acid, progesterone antagonists, IFB-088, ADX71441, and ACE-083. This review is to sum up the pathogenesis of CMT1A and promising targeting drug therapies for further research.

2018-06-01·Muscle & nerve3区 · 医学

Locally acting ACE‐083 increases muscle volume in healthy volunteers

3区 · 医学

Article

作者: Glasser, Chad E. ; Sherman, Matthew L. ; Gartner, Michael R. ; Wilson, Dawn ; Attie, Kenneth M. ; Miller, Barry

ABSTRACT:

Introduction: ACE‐083 is a locally acting follistatin‐based therapeutic that binds myostatin and other muscle regulators and has been shown to increase muscle mass and force in neuromuscular disease mouse models. This first‐in‐human study examined these effects. Methods: In this phase 1, randomized, double‐blind, placebo‐controlled, dose‐ranging study in healthy postmenopausal women, ACE‐083 (50–200 mg) or placebo was administered unilaterally into rectus femoris (RF) or tibialis anterior (TA) muscles as 1 or 2 doses 3 weeks apart. Results: Fifty‐eight postmenopausal women were enrolled, 42 ACE‐083 and 16 placebo. No serious adverse events (AE), dose‐limiting toxicities, or discontinuations resulting from AEs occurred. Maximum (mean ± SD) increases in RF and TA muscle volume were 14.5% ± 4.5% and 8.9% ± 4.7%, respectively. No significant changes in mean muscle strength were observed. Discussion: ACE‐083 was well tolerated and resulted in significant targeted muscle growth. ACE‐083 may have the potential to increase muscle mass in a wide range of neuromuscular disorders. Muscle Nerve57: 921–926, 2018

项与 Efmitermant alfa 相关的新闻（医药）

2021-08-21

·药时代

特别报道 - 明星公司今何在？十年过去了，这些生物技术公司还好吗？（上）

正文共： 6488字 21图预计阅读时间： 17分钟（图片来源：Fierce Biotech官网） FIERCE Biotech是全球知名的专业媒体，推出的“Fierce 15”栏目在业内享有盛誉。每年他们评出15家生物技术公司，入选“Fierce 15”。中文被翻译成“全球最强生物技术公司”或“全球最佳生物技术公司”，也有翻译成“全球最凶猛生物技术公司”、“全球最威猛生物技术公司”。该竞赛旨在发掘那些具有远见和管理专业知识的公司，它们改变了医生治疗疾病的方式或改进药物开发过程的技术，或者朝着这个伟大的方向挺进。过去这些年里，超过250家公司在年度竞赛中成功晋级决赛，今年已经是第18个年头了。据说，创业公司活过5年的少之又少，所以，不可避免的是那些获得“Fierce 15”殊荣而名扬天下的公司中有成功者，有失败者，也有逃跑者。 2020年9月14日，Fierce Biotech发表文章“Where are they now? Tracking down 2010’s Fierce 15”，对2010年获得殊荣的十五家公司进行了跟踪报道，看看这十年里这些公司发生了怎样的变化，他们的创新想法是否经得起时间的考验，也就是我们现在常说的是否是“时间的朋友”。（图片来源：Fierce Biotech官网）在当年金榜题名的15家公司中，有8家已被收购或合并，值得注意的是，这些交易中有一半涉及百时美施贵宝/新基，另外6家仍在独立运营，只有一家已不复存在。这是一个相当不错的成功率，特别是15家公司中有6家公司不仅经受住了岁月的考验，而且还成功地将候选药物推进临床试验，越过新药开发充满风险的漫漫征途，最终推向了市场。需要特别指出的是，那些最终获批上市的药物并不总是评选之时公司管线中的候选药物，甚至并非源自2010年公司被宣传介绍时的平台。十年也短暂也漫长，可能会发生很多事情，对于生物技术这样的行业来说，变化实在是再正常不过了。当然，能够快速调头而把握新机遇是一家优秀生物技术公司的标志。为了给同药们提供最大的价值，我们在编译原文的同时，也就每一家公司进行“药时代点评”，补充公司当下的最新状况。水平、时间有限，疏漏错误难免，热烈欢迎大家补充、指正！（一）Acceleron Pharma 总部：马萨诸塞州剑桥成立时间：2003 首席执行官：Habib Dable 2010年，Acceleron已经发展成为一家很不错的新兴生物技术公司。它与夏尔（已被武田于2019年1月收购）和新基（已被百时美施贵宝于2019年11月收购）建立了几个大规模合作伙伴关系，其治疗杜氏肌营养不良症的主要药物ACE-03正在进入中期开发阶段。骨质流失、贫血和癌症方面的早期项目也已启动。 Acceleron 2010年，Acceleron已经发展成为一家很不错的新兴生物技术公司。它与夏尔（已被武田于2019年1月收购）和新基（已被百时美施贵宝于2019年11月收购）建立了几个大规模合作伙伴关系，其治疗杜氏肌营养不良症的主要药物ACE-03正在进入中期开发阶段。骨质流失、贫血和癌症方面的早期项目也已启动。 2013年，公司完成大规模IPO，为其药物组合的临床试验提供资金，所有这些药物都是调节转化生长因子 β (TGF-β) 蛋白质超家族。从那时起，尽管多年来面临许多挫折，Acceleron与BMS合作的Rebrozyl（luspatercept）已于2019年11月8日获FDA批准。FDA批准该药物治疗需要常规红细胞输血的β地中海贫血患者以及与骨髓增生异常综合征（MDS）相关的贫血患者。它在6月份在欧洲获得了相同的批准。 Rebrozyl被誉为第一个进入市场的新型红细胞成熟剂 (EMA)，被杰富瑞 (Jefferies) 的分析师预测为潜在的20亿美元重磅炸弹。它的大部分销售潜力被认为在于MDS，因为患有这种疾病的患者更多，bluebird bio的基因疗法Zynteglo可能会减少其在地中海贫血的市场。 Zynteglo在美国的开发面临一些延误，已经在欧洲被批准用于治疗地贫。 Luspatercept（前身为 ACE-536）是2010年管线中的两个幸存者之一，另一个是 sotatercept（ACE-011），后者在地中海贫血临床研究中被淘汰，但仍在进行肺动脉高压（PAH）的临床测试，并在2020年早些时候在2期试验中达到终点。针对PAH的3期注册性临床试验将于2020年底前开始。sotatercept还获得了FDA的突破性疗法资格和EMA的优先药物（PRIME）资格，这对于Acceleron发现的药物和迄今为止的任何PAH药物来说，这都是第一次。肌肉生长抑制素抑制剂ACE-031难逃同类其它药物的命运，在DMD试验中失败，后续药物ACE-083在面肩肱型肌营养不良症和Charcot-Marie-Tooth (CMT) 疾病中也未达标，最终于2020年被放弃。2010年的另一个项目，dalantercept (ACE-041)，在 2期肾癌试验中失败，于2017年被停止。随着Rebrozyl和进入后期开发的另一款药物即将产生收入，Acceleron在2010年“Fierce 15 班级”中稳稳地跻身成功者行列。尽管受到COVID-19危机的拖累，该公司在2020年第二季度从Rebrozyl的5500万美元销售额中获得了1100万美元的特许权使用费，并且在EMA批准该药物后，该公司还从其合作伙伴那里获得了2500万美元的里程碑付款。药时代点评药时代点评：今天，当我们打开Acceleron公司的官网，我们看到一个拥有上市产品的上市公司，公司目前股价为124.81美元，公司市值76亿美元。公司的管线非常聚焦。公司获得“Fierce 15”称号时只有7岁，而今已经18岁了。管线非常聚焦和扎实。（图片来源：公司官网）我们祝愿这位正值韶华的Acceleron继续乘风破浪，明天更美好！（二）Adimab 总部: 总部: Lebanon, New Hampshire成立时间: 2007CEO: Tillman Gerngros 成立时间: 总部: Lebanon, New Hampshire成立时间: 2007CEO: Tillman Gerngros CEO: 总部: Lebanon, New Hampshire成立时间: 2007CEO: Tillman Gerngros 早在2010年，Adimab就为其抗体药物发现技术建立了一些合作，在此期间它一定做得很好。截至2020年上半年，该生物技术公司已与超过75家制药和生物技术公司合作，产生了340多个治疗项目，其中40个已进入临床试验。 Adimab没有开发自己的抗体药物，而是将其基于酵母细胞的表达平台用于为客户发现和优化抗体，包括双特异性药物。它说这种方法比传统技术更快、更容易，例如噬菌体展示技术或在动物系统中制造抗体。一些合作项目在Adimab的内部开展工作，而其它合作项目则将其技术转移给合作伙伴的科学家。 GlaxoSmithKline、Biogen、Novo Nordisk、Merck & Co、Eli Lilly和Takeda都在其研发部门内使用Adimab的发现技术，Adimab的抗体项目中的大约三分之二来自这些“平台转移”交易，这通常涉及未来产品销售的首付款、里程碑付款和特许权使用费。许多交易都是大手笔，但由于新药开发的失败率很高，成功的最佳标志是产品批准，而Adimab实现了这一目标，合作伙伴来自中国，那就是信达生物。2018年12月27日，信达生物制药携手礼来制药共同宣布，双方共同开发的创新肿瘤药物达伯舒®（重组全人源抗PD-1单克隆抗体，化学通用名：信迪利单抗注射液）正式获得国家药品监督管理局的批准，用于至少经过二线系统化疗的复发或难治性经典型霍奇金淋巴瘤的治疗。 2020年，这款PD-1药物的非小细胞肺癌适应症申请也在中国接受审评，礼来同意了一项价值超过10亿美元的许可协议，以在美国和其它地方开发该产品。 2020年标志着Adimab的另一个重要里程碑，当时它推出了Adagio Therapeutics，一个致力于利用Adimab的平台开发自己的药物的拆分公司。顺应2020年的需求，Adagio正在研究可以预防冠状病毒的抗体，包括COVID-19大流行背后的菌株SARS-CoV-2。自成立以来，Adimab一直没有上市，到2015年，在一系列后期风险投资之后，它的价值已经超过10亿美元。它当然可以被视为2010年这一“班级”里的又一个成功者。药时代点评药时代点评： Adimab公司最令我们惊艳的是它的合作伙伴矩阵，可谓是明星荟萃，大咖云集。（图片来源：公司官网）公司非常自豪地宣称自己已经帮助合作伙伴推进40多款药物进入临床试验阶段。另一个吸睛之处就是Adimab的博士前项目（Predoctoral Program）。这个独特的历时24个月的项目为青年学生提供在创新性创业环境中积累有意义的研究经验的宝贵机会，专为希望在进入顶级研究生课程之前获得两年行业经验的个人而设计。该计划的毕业生都进入了世界名校。（图片来源：公司官网）（三）Alder Biopharmaceuticals 总部: 总部: Bothell, Washington成立于: 2004CEO: n/a 成立于: 总部: Bothell, Washington成立于: 2004CEO: n/a CEO: 总部: Bothell, Washington成立于: 2004CEO: n/a 2010年，Alder Biopharmaceuticals仍处于起步阶段，尽管该公司刚刚与百时美施贵宝签署了10亿美元的协议，势头正盛。2019年10月，该生物技术公司不复存在，被丹麦制药商灵北以20亿美元的价格收购，该收购源于对偏头痛药物依替尼单抗（eptinezumab）的竞购战。收购后，公司更名为灵北西雅图生物制药公司。有意思的是，2010年，依替珠单抗还没有踪影。 2020年2月21日，FDA批准了依替尼单抗用于预防成人偏头痛，商品名VYEPTI™。这是第一个用于预防偏头痛的静脉疗法，让灵北有机会进军CGRP抑制剂偏头痛市场，与安进和诺华、礼来和梯瓦的药物抗衡，争夺市场份额。2019年，安进和诺华的Aimovig的销售额为3.06亿美元，礼来的Emgality为1.62亿美元，梯瓦的Ajovy为9300万美元。 Aimovig、Emgality和Ajovy都是通过皮下注射给药的，Vyepti是同类产品中第一个通过静脉输液给药的。这意味着它可以每12周给药一次，据Alder称其药物起效更快。相比之下，它的竞争对手每个月都需要注射。不过，一些医生表示，他们将使用Vyepti作为备用选择，因为它需要在诊所进行管理，这促使Jefferies的分析师建议它最终可能会成为一个利基产品。2020年，艾伯维（AbbVie）和Biohaven等竞争对手的偏头痛口服疗法处于后期临床研究，有望提供对患者更友好的替代方案。对于灵北而言，Vyepti符合其总体规划，将重点放在更广泛的中枢神经系统疾病上，超出其抑郁症和精神分裂症等精神病核心领域，实现销售多元化。不过，这笔交易并不完全是关于Vyepti。2019年，Alder开始了垂体腺苷酸环化酶激活多肽 (PACAP) 抑制剂ALD1910的临床试验，它有可能成为一种避开拥挤的CGRP类别的偏头痛预防药物。也有传言称Alder将成为灵北的抗体开发中心，这样可以充分利用其基于酵母的制造方法。 Alder在2010年的最大希望是与BMS合作的治疗类风湿性关节炎的IL-6抑制剂clazakizumab (ALD518)。该药物在BMS公司开展产品组合优先排序后于2014年回归Alder，但几年后它找到了一个新家，加拿大初创公司Vitaeris，该公司“老药新用”，开发该药物防止移植患者出现排斥反应。在6月份达成收购协议后，Vitaeris和clazakizumab成为CSL Behring的一部分。药时代点评： Alder Biopharmaceuticals公司的官网已经无法访问。药时代将继续关注Vyepti这款药物。（四）Amira Pharmaceuticals 总部: 总部: San Diego成立于: 2005CEO: n/a 成立于: 总部: San Diego成立于: 2005CEO: n/a CEO: 总部: San Diego成立于: 2005CEO: n/a Amira Pharma在入选 “Fierce 15”几个月后，于2011年7月被Bristol Myers Squibb 以3.25亿美元的现金预付款（外加1.5亿美元的额外里程碑付款）收购。这是2010年榜单中第二个被大型制药公司收购的公司。 Amira于2005年由三位科学家——Peppi Prasit、Jilly Evans和John Hutchinson创立，他们曾在默沙东公司合作，在哮喘重磅药物Singulair（孟鲁司特）方面取得了巨大成功。被收购之时，拥有17年安进工作经验的鲍勃·巴尔特拉领导公司，他后来成为Cirius Therapeutics的首席执行官。 BMS寻求的主要标的是名为AM152的小分子药。该药旨在治疗特发性肺纤维化和系统性硬化症 (SSc) ，该分子靶向LPA1受体，之后更名为BMS-986020。由于肝胆毒性，特发性肺纤维化以及后续适应症银屑病的适应症开发被迫于2019年中止。 BMS还选择了一个处于临床前的autotaxin（ATX）项目，该项目可能对治疗神经性疼痛和癌症转移有用，但它没有出现在公司的管线清单中。 Amira引人关注的是在2008年与葛兰素史克达成4.25亿美元的合作之后，该合作专注于以AM103（GSK 2190914）为首的呼吸和心血管疾病候选药物，这是一款5-脂氧合酶激活蛋白 (FLAP) 抑制剂。它似乎与同类其它药物一起被搁置了起来，好像不是很顺利。药时代点评：祝贺公司找到了非常好的归宿！（五）Anchor Therapeutics 总部: 总部: Cambridge, Massachusetts成立于: 2008CEO: n/a 成立于: 总部: Cambridge, Massachusetts成立于: 2008CEO: n/a CEO: 总部: Cambridge, Massachusetts成立于: 2008CEO: n/a Anchor Therapeutics在2010年有很多进展。它有一项专注于G蛋白偶联受体 (GPCR) 的技术，GPCR是药物开发领域中一个成熟且富有成果的靶点。公司从风险投资人那里筹集了3000万美元；并先后与诺华和强生签署了首个合作伙伴关系，价值分别为2亿美元和4.8亿美元。 Anchor的前景在于其pepducin技术平台，该平台基于与疏水性脂质部分结合的短合成肽的使用。短合成肽可以渗透到细胞内膜上的受体，比大多数靶向小分子靶向并调节GPCR信号的效果要好得多。其最领先的项目靶向CXCR4受体，具有吸引干细胞以帮助治愈骨骼和心血管损伤的潜力。该公司的首席执行官Frederick Jones，现在在投资集团BioAdvance任职，甚至一度将该平台比作单克隆抗体和RNA干扰革命的开端。然而，公司的候选化合物似乎都没有跨越临床前开发阶段。Anchor于2013年停止更新其网站，因此推定其已不复存在。药时代点评：该公司应该是2010年15家“Fierce 15”明星公司中唯一一家以令人感到遗憾的方式退场的创业公司。这再次例证了新药研发不易，九死一生。接下来，我们将分享“特别报道 | 明星公司今何在？十年过去了，这些生物技术公司还好吗？（中）”、“特别报道 | 明星公司今何在？十年过去了，这些生物技术公司还好吗？（下）”。敬请同药们关注！谢谢！ —END—

合作并购抗体免疫疗法小分子药物

2020-04-08

·BioSpace

Acceleron’s Clinical PAH Drug Wins Breakthrough Therapy Designation

The designation will allow the company to expedite the development and potential regulatory review of sotatercept. Following positive Phase II data earlier this year, Acceleron Pharma ’s experimental pulmonary arterial hypertension (PAH) treatment sotatercept won Breakthrough Therapy designation from the U.S. Food and Drug Administration. The designation will allow the company to expedite the development and potential regulatory review of sotatercept, an investigational agent designed to be a selective ligand trap for members of the TGF-beta superfamily to rebalance BMPR2 signaling, which is a key molecular driver of PAH. Last year, sotatercept received Orphan Drug Designation from the FDA. Looking at the positive Phase II results posted in January, Acceleron Chief Executive Officer Habib Dable believes sotatercept has the “potential to shift the current treatment paradigm” and provide a significant benefit to PAH patients beyond currently available therapies. If approved, sotatercept would compete with PAH drugs already on the market, such as United Therapeutics top-selling PAH drug, Remodulin. Other approved drugs include Actelion’s Tracleer and Pfizer’s Revatio. Habib said the company is “thrilled” with the designation, which he said is a first for an Acceleron-discovered medicine and for a therapeutic candidate in PAH. In the PULSAR Phase II trial, sotatercept demonstrated a “statistically significant reduction in pulmonary vascular resistance” (PVR), the trial’s primary endpoint, at week 24 versus placebo. The trial also achieved a statistically significant improvement in the key secondary endpoint of six-minute-walk-distance (6MWD), as well as other secondary endpoints, including NT-proBNP, and WHO functional class. Over the 24-week period of treatment, Acceleron said sotatercept was generally well-tolerated in the trial. Adverse events observed in the study were generally consistent with previously published data on sotatercept in other diseases. Pulmonary arterial hypertension is a rare and chronic, rapidly progressing disorder characterized by the constriction of small pulmonary arteries and elevated blood pressure in the pulmonary circulation. The 5-year survival rate for patients with PAH is approximately 57%. The Breakthrough Therapy designation comes on the heels of Acceleron’s decision to abandon the development of ACE-083, an experimental treatment for Charcot-Marie-Tooth disease. In March, Acceleron reported the drug failed to demonstrate itself in a mid-stage trial. As BioSpace previously reported , ACE-083 showed a statistically significant increase in mean total muscle volume, which was the primary endpoint of the trial. However, the experimental drug did not lead to statistically significant improvements in function or quality of life secondary endpoints. Charcot-Marie-Tooth disease is a common inherited neurological disorder. The disease is made up of a group of disorders that affect peripheral nerves, which are those nerves outside the brain and spinal cord. It affects motor and sensory nerves and includes weakness of the foot and lower leg muscles. ACE-083 was the company’s lead product candidate for its neuromuscular therapeutic program. It is designed to bind to and inhibit specific proteins in the TGF-beta protein superfamily that reduce muscle growth, such as activins and myostatins (GDF8).

临床2期孤儿药临床结果突破性疗法

2020-03-10

·BioSpace

Acceleron Abandons Charcot-Marie-Tooth Program After Trial Failure

ACE-083 was the company’s lead product candidate for its neuromuscular therapeutic program. Cambridge, Massachusetts-based Acceleron Pharma announced that its Phase II clinical trial of ACE-083 in patients with Charcot-Marie-Tooth disease (CMT) failed to show functional improvement. The company indicated the drug did show a statistically significant increase in mean total muscle volume, which was the primary endpoint of the trial, but it didn’t lead to statistically significant improvements in function or quality of life secondary endpoints. Acceleron says it is discontinuing development of the drug. CMT is one of the most common inherited neurological disorders. It is made up of a group of disorders that affect peripheral nerves, which is to say, those outside the brain and spinal cord. It affects motor and sensory nerves and includes weakness of the foot and lower leg muscles. There are often foot deformities, such as high arches and hammertoes because of weakness of the small muscles in the feet. It affects about one in 2,500 people in the U.S. ACE-083 was the company’s lead product candidate for its neuromuscular therapeutic program. It is designed to bind to and inhibit specific proteins in the TGF-beta protein superfamily that reduce muscle growth, such as activins and myostatins (GDF8). “Unfortunately, over the course of multiple clinical trials, our myostatin-plus hypothesis has not resulted in the functional outcomes necessary to provide clinically meaningful benefits for patients with neuromuscular diseases,” said Habib Dable, president and chief executive officer of Acceleron. “We wish to thank all the patients, families, caregivers, and investigators for their support and participation in this research. I also want to acknowledge our team’s hard work and commitment to executing robust Phase II trials that have provided us the data necessary to make the difficult but informed investment decision to discontinue the program.” The company plans to refocus its resources on hematology with its Reblozyl in anemia and on pulmonary with sotatercept in pulmonary arterial hypertension (PAH). The Phase II trial evaluated ACE-083 in CMT patients who had muscle weakness in the tibialis anterior (TA), a muscle in the lower leg involved in raising the foot at the ankle. Part 1 of the trial was an open-label, dose-escalation study. ACE-083 was dosed by injection into the TA muscle once every three weeks in 18 patients to determine the safety and increases in muscle volume over a three-month period. Part 2 was a randomized, double-blind, placebo-controlled study that leveraged the optimal dose level chosen in Part 1. A total of 44 patients were involved in the trial in Part 2, receiving either ACE-083 or placebo. They were evaluated for changes in muscle volume, fat fraction, strength, function, quality of life, and safety over a six-month period, followed by a six-month open-label treatment period. In November 2019, the company’s Reblozyl (luspatercept-aamt) was the first and only erythroid maturation agent approved by the FDA to treat anemia in adults with beta-thalassemia who require regular red blood cell transfusions. At the company’s fourth quarter and full year 2019 report on February 27, 2020, Dable said, “While our hematology program remains a top priority, we are equally excited by the progress we are making in pulmonary disease. We recently announced positive topline results from the PULSAR Phase II trial of sotatercept for the treatment of PAH. These data introduce the possibility that sotatercept could potentially change the way physicians treat patients with PAH.” hbspt.forms.create({ portalId: "4413123", formId: "c4dda430-e2b0-4083-86f3-ccce0c1d4479" });

临床2期临床结果上市批准

100 项与 Efmitermant alfa 相关的药物交易

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10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
X-连锁腓骨肌萎缩症1	临床2期	美国	Acceleron Pharma, Inc.	2019-05-10
X-连锁腓骨肌萎缩症1	临床2期	加拿大	Acceleron Pharma, Inc.	2019-05-10
X-连锁腓骨肌萎缩症1	临床2期	西班牙	Acceleron Pharma, Inc.	2019-05-10
面肩肱型肌营养不良	临床2期	美国	Acceleron Pharma, Inc.	2016-11-01
面肩肱型肌营养不良	临床2期	加拿大	Acceleron Pharma, Inc.	2016-11-01
面肩肱型肌营养不良	临床2期	西班牙	Acceleron Pharma, Inc.	2016-11-01

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适应症

分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03124459 (Phase 2 Study of ACE-083, CTgov)	临床2期	腓骨肌萎缩症	63	ACE-083	範憲鑰齋範齋選簾繭憲(廠鏇觸鏇壓鬱範淵壓積) = 鏇醖窪夢廠窪鑰糧衊夢廠構艱餘鹹鬱獵範簾願 (淵齋艱夢襯構壓窪鬱鑰, 鏇艱鹹醖襯廠夢製襯齋 ~ 願遞齋糧醖壓廠壓選選) 更多	-	2021-07-28
NCT03943290 (CTgov)	临床2期	X-连锁腓骨肌萎缩症1 \| 面肩肱型肌营养不良	62	ACE-083 (Part 2 Cohort 2a)	夢積構憲製顧憲範繭鏇 = 艱餘繭築鑰鬱遞鑰餘廠築鏇積齋製憲鑰遞齋繭 (製憲獵製醖簾齋積壓築, 鹹鏇築夢鹽觸衊網簾醖 ~ 鑰艱壓淵簾壓獵壓遞簾) 更多	-	2021-06-02
				ACE-083 (Part 2 Cohort 2b)	夢積構憲製顧憲範繭鏇 = 窪廠積蓋鹹齋築憲壓構築鏇積齋製憲鑰遞齋繭 (製憲獵製醖簾齋積壓築, 簾構蓋淵窪觸窪構襯餘 ~ 艱鬱窪築鏇繭壓壓遞鏇) 更多
NCT02927080 (BusinessWire) 人工标引	临床2期	面肩肱型肌营养不良	-	Efmitermant alfa	鏇願鑰遞襯積選鹹網鏇(憲壓鹽鏇襯鏇鑰範鬱簾) = Adverse events were mostly mild to moderate (Grade 1 or 2) and injection-site related 築蓋膚顧夢繭艱衊膚遞 (鬱網窪齋窪糧襯鬱簾願 ) 更多	不佳	2019-09-16
				Placebo
NCT02257489 (CTgov)	临床1期	肌肉骨骼系统疾病	58	placebo+ACE-083 (50 mg Single Dose (RF))	膚襯選繭蓋壓選廠醖顧 = 繭衊淵觸獵製鬱膚製選繭獵鹹蓋築構範顧艱夢 (獵範鏇糧範鹹簾廠鹽齋, 鹽願網製壓鹹簾膚齋淵 ~ 鬱網繭範簾繭窪膚願餘) 更多	-	2019-07-08
				placebo+ACE-083 (100 mg Single Dose (RF))	膚襯選繭蓋壓選廠醖顧 = 繭築夢積獵壓淵觸憲鏇繭獵鹹蓋築構範顧艱夢 (獵範鏇糧範鹹簾廠鹽齋, 遞鹹網網選築夢餘繭獵 ~ 鏇憲壓艱構構衊製選鑰) 更多
S58.006 (AAN2019)	临床2期	腓骨肌萎缩症	24	ACE-083 150 mg/muscle	蓋繭鹽糧鹽構窪遞夢鹹(膚繭簾顧觸衊積齋鏇構) = 範願範憲廠範範餘糧憲範範獵淵糧夢積壓憲齋 (獵蓋餘顧遞鏇鑰範鬱鏇 ) 更多	积极	2019-04-09
				ACE-083 200 mg/muscle	蓋繭鹽糧鹽構窪遞夢鹹(膚繭簾顧觸衊積齋鏇構) = 獵繭鏇壓鹽遞廠鏇蓋蓋範範獵淵糧夢積壓憲齋 (獵蓋餘顧遞鏇鑰範鬱鏇 ) 更多
S38.001 (AAN2018)	临床2期	面肩肱型肌营养不良	-	ACE-083	齋網鑰願壓餘窪鑰餘鏇(觸淵廠鏇遞願獵襯窪憲) = myalgia occurred in patients treated with ACE-083 齋齋製壓壓壓夢鏇鑰淵 (淵壓願餘餘鏇選鬱艱醖 ) 更多	-	2018-04-10