Opicinumab(Opicinumab) - 药物靶点：LINGO-1_专利_临床

概要

基本信息

药物类型

单克隆抗体

别名

ANTI-LINGO 1、ANTI-LINGO-1、Anti-LINGO-1 antibody

+ [2]

靶点

LINGO-1

作用机制

LINGO-1抑制剂(富含亮氨酸重复序列和免疫球蛋白结构域的Nogo受体作用蛋白-1抑制剂)、细胞分化刺激剂

治疗领域

免疫系统疾病神经系统疾病眼部疾病+ [1]

在研适应症-

非在研适应症

复发性多发性硬化RRMS视神经炎

原研机构

Biogen, Inc.

Dyax Corp.

在研机构-

非在研机构

Biogen, Inc.

最高研发阶段终止临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

序列信息

Sequence Code 1311317H

来源: *****

Sequence Code 9535515L

来源: *****

关联

16

项与 Opicinumab 相关的临床试验

NCT03222973 / Terminated临床2期

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study With Optional Open-Label Extension in Subjects With Relapsing Multiple Sclerosis to Evaluate the Efficacy and Safety of BIIB033 as an Add-On Therapy to Anti-Inflammatory Disease-Modifying Therapies

The primary objective of Part 1 of this study is to evaluate the effects of BIIB033 versus placebo on disability improvement over 72 weeks. The primary objective of Part 2 of this study is to evaluate the long-term safety profile of BIIB033 as an add-on therapy in participants with MS.
The secondary objective of Part 1 is to evaluate the effects of BIIB033 versus placebo on additional measures of disability improvement. The secondary objective of Part 2 is to investigate long-term efficacy (disability improvement) and additional safety measures of BIIB033 as an add-on therapy in participants with MS.

开始日期2017-11-15

申办/合作机构

Biogen, Inc.

NCT02833142 / Completed临床1期

A Randomized, Blinded, Parallel-Group, Phase 1 Study of Pharmacokinetics, Safety and Tolerability of Single Intravenous Doses of BIIB033 (Opicinumab ) Produced by 2 Manufacturing Processes, in Healthy Volunteers

The primary objective of the study is to characterize the pharmacokinetics (PK) of BIIB033-B and to compare the PK profile with that of BIIB033-A in healthy volunteers. Secondary objectives are: To assess the safety and tolerability of BIIB033-A and BIIB033-B; To assess the secondary PK parameters of BIIB033-A and BIIB033-B; To assess the immunogenicity of BIIB033-A and BIIB033-B.

开始日期2016-07-01

申办/合作机构

Biogen, Inc.

NCT02657915 / Completed临床2期

A Multicenter, Follow-Up Study to Assess Long-Term Electrophysiologic and Clinical Outcomes in Subjects Previously Enrolled in Study 215ON201

The primary objective of the study is to assess full-field visual evoked potential (FF-VEP) latency in subjects who were enrolled in Study NCT01721161 2 years (+ up to 12 months) after the last study visit. The secondary objective is to assess clinical progression and severity of central nervous system (CNS) demyelinating disease in subjects who were enrolled in Study NCT01721161 2 years (+ up to 12 months) after the last study visit. Intervention was administered in the previous study. The participants, investigator and outcome assessors remain blinded in this follow-up study.

开始日期2016-03-10

申办/合作机构

Biogen, Inc.

100 项与 Opicinumab 相关的临床结果

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100 项与 Opicinumab 相关的转化医学

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100 项与 Opicinumab 相关的专利（医药）

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54

项与 Opicinumab 相关的文献（医药）

2024-07-01·Current neuropharmacology

Disease Modifying Strategies in Multiple Sclerosis: New Rays of Hope to Combat Disability?

Review

作者: Bonaventura, Gabriele ; Cantarella, Giuseppina ; Di Mauro, Rosaria ; Cantone, Anna Flavia ; Di Benedetto, Giulia ; Mariottini, Alice ; Bellanca, Carlo Maria ; La Cognata, Valentina ; Augello, Egle ; Massacesi, Luca ; Attaguile, Giuseppe ; Bernardini, Renato

Abstract::

Multiple sclerosis (MS) is the most prevalent chronic autoimmune inflammatory- demyelinating disorder of the central nervous system (CNS). It usually begins in young adulthood, mainly between the second and fourth decades of life. Usually, the clinical course is characterized by the involvement of multiple CNS functional systems and by different, often overlapping phenotypes. In the last decades, remarkable results have been achieved in the treatment of MS, particularly in the relapsing- remitting (RRMS) form, thus improving the long-term outcome for many patients. As deeper knowledge of MS pathogenesis and respective molecular targets keeps growing, nowadays, several lines of disease-modifying treatments (DMT) are available, an impressive change compared to the relative poverty of options available in the past. Current MS management by DMTs is aimed at reducing relapse frequency, ameliorating symptoms, and preventing clinical disability and progression. Notwithstanding the relevant increase in pharmacological options for the management of RRMS, research is now increasingly pointing to identify new molecules with high efficacy, particularly in progressive forms. Hence, future efforts should be concentrated on achieving a more extensive, if not exhaustive, understanding of the pathogenetic mechanisms underlying this phase of the disease in order to characterize novel molecules for therapeutic intervention. The purpose of this review is to provide a compact overview of the numerous currently approved treatments and future innovative approaches, including neuroprotective treatments as anti-LINGO-1 monoclonal antibody and cell therapies, for effective and safe management of MS, potentially leading to a cure for this disease.

2024-01-01·Neuroscience letters

Antagonizing LINGO-1 reduces activated microglia and alleviates dendritic spine loss in the hippocampus of APP/PS1 transgenic mice

Article

作者: Wang, Jin ; Yang, Hao ; Xie, Yu-Han ; Zhu, Lin ; Chao, Feng-Lei ; Luo, Yan-Min ; Zhou, Yu-Ning ; Deng, Yu-Hui ; He, Qi ; Zhou, Chun-Ni ; Jiang, Lin ; Huang, Du-Juan ; Zhang, Yi ; Liang, Xin ; Tang, Yong

In Alzheimer's disease (AD), microglia are involved in synaptic pruning and mediate synapse loss. LINGO-1 is a negative regulator of nerve growth, and whether antagonizing LINGO-1 can attenuate synaptic pruning by microglia and rescue dendritic spines in the hippocampus in AD is still unclear. On this basis, the anti-LINGO-1 antibody, which binds to LINGO-1 protein and antagonizes the effects of LINGO-1, was administered to 10-month-old APP/PS1 transgenic mice for 2 months. The Morris water maze test, immunohistochemical and stereological methods, immunofluorescence and 3D reconstruction were used. Compared to wild-type mice, APP/PS1 transgenic mice had worse performance on behavioral tests, fewer dendritic spines but more microglia in the hippocampus. Meanwhile, the microglia in APP/PS1 transgenic mice had more branches of medium length (4-6 µm) and a cell body area with greater variability. Moreover, APP/PS1 transgenic mice had more postsynaptic termini colocalized with microglia in the hippocampus than wild-type mice. The anti-LINGO-1 antibody significantly reversed these changes in AD, indicating that the anti-LINGO-1 antibody can improve hippocampus-dependent learning and memory abilities and effectively rescue dendritic spines in the hippocampus of AD mice and that microglia might participate in this progression in AD. These results provide a scientific basis for further studying the mechanism of the anti-LINGO-1 antibody in AD and help to elucidate the role of LINGO-1 in the treatment of AD.

2023-08-01·Neuroscience research

Anti-LINGO-1 antibody protects neurons and synapses in the medial prefrontal cortex of APP/PS1 transgenic mice

Article

作者: Zhou, Yu-Ning ; Xiao, Qian ; Yang, Hao ; Jiang, Lin ; He, Qi ; Tang, Yong ; Wang, Yi-Ying ; Chao, Feng-Lei ; Zhou, Chun-Ni ; Huang, Du-Juan ; Zhang, Yi ; Luo, Yan-Min

The medial prefrontal cortex (mPFC), one of the most vulnerable brain regions in Alzheimer's disease (AD), plays a critical role in cognition. Leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein-1 (LINGO-1) negatively affects nerve growth in the central nervous system; however, its role in the pathological damage to the mPFC remains to be studied in AD. In this study, an anti-LINGO-1 antibody was administered to 10-month-old APP/PS1 mice, and behavioral tests, stereological methods, immunohistochemistry and immunofluorescence were used to answer this question. Our results revealed that LINGO-1 was highly expressed in the neurons of the mPFC of AD mice, and the anti-LINGO-1 antibody improved prefrontal cortex-related function and reduced the protein level of LINGO-1, atrophy of the volume, Aβ deposition and massive losses of synapses and neurons in the mPFC of AD mice. Antagonizing LINGO-1 could effectively alleviate the pathological damage in the mPFC of AD mice, which might be an important structural basis for improving prefrontal cortex-related function. Abnormal expression of LINGO-1 in the mPFC may be one of the key targets of AD, and the effect initiated by the anti-LINGO-1 antibody may provide an important basis in the search for drugs for the prevention and treatment of AD.

1

项与 Opicinumab 相关的新闻（医药）

2023-04-13

·药时代

Biogen收缩占年收入一半的「最」核心业务，这是不是叫该收手时就收手

文章来源药时代Biogen在砍自己的核心业务。据《波士顿商业杂志》消息，Biogen已告知其部分美国员工将被裁员，受影响的主要是Biogen的MS（多发性硬化症）团队，但具体裁员岗位类型尚不明确。这一消息令人“困惑”。因为对于Biogen而言，MS治疗药物是最核心的收入来源。根据Biogen2022年财报，Biogen该年度收入为101.73亿美元，其中MS产品收入为54.3亿美元，占据Biogen年收入的53.3%。Biogen这两年怎么混成这样了？到底是Biogen出了问题，还是MS这个领域不行了？01从神坛输到一败涂地2022年，Biogen的总收入同比下滑了7.36%，净利润却同比增长了71.43%，达到29.62亿美元。但细读财报，Biogen的净利润增长水分很大，与产品销售情况基本无关。2022年，Biogen出售了自己原先持有的三星Bioepis公司股权给三星生物，换来了23亿美元（10亿美元已交付）；同时出售了部分持有的地产获得5亿美元。相当于产品带来的利润只有14亿美元左右。同时，Biogen还削减了十分之一的研发投入，并进行了一次大规模裁员。总收入的下滑与Biogen在最擅长的MS领域马失前蹄有关。如果仅就已上市MS药物数量而言，Biogen依然是老大，手握五款MS治疗药物，按理说应该吃香的喝辣的。只可惜风云突变，2017年，罗氏（基因泰克）打磨了14年的CD20抑制剂Ocrevus（奥瑞珠单抗 ocrelizumab）横空出世，一脚踢飞市面上所有MS治疗药物。上市五年，迅速卷走MS市场份额，到了2022年，Ocrevus销售额高达65.39亿美元，比Biogen5款MS药物销售额加起来都多。事实上，Ocrevus已经成为了罗氏最大的一棵“摇钱树”。但如果只是Ocrevus拦路，那么Biogen也完全可以保住自己的基本盘，可更糟心的事接踵而至。Biogen最主要的MS治疗药物TECFIDERA的核心专利原本2028年才会到期，但在2017年遭遇了仿制药巨头迈兰（Mylan，现属于Viatris）的专利挑战。在4年官司拉锯战之后，Biogen败诉，迈兰的TECFIDERA仿制药在2021年8月成功上市销售，有了迈兰撕开的口子，其它仿制药企业也蜂拥而上。于是我们能看到，2022年TECFIDERA的销售额近乎腰斩……看看隔壁的修美乐，二十几年滴水不漏，Biogen的这次攻防只能以悲剧来形容。一款原研药的生命周期总共才几年？今年3月2日，Biogen和卫材终止了自2018年就开始的联合推广协议。在此之前，卫材负责在日本地区与Biogen联合推广Biogen的MS治疗药物。两家药企宣布，终止合作协议的原因是“产品在日本市场的渗透已经达到一定的目标”。这个“已经达到一定的目标”很耐人寻味。02下一步全力投入阿尔兹海默病？尽管略显仓促，但Biogen确实应该从MS领域抽身出来了。2020年，Biogen的MS新药opicinumab，2期临床试验因疗效未达预期而暂停。由于opicinumab曾表现出修复神经末梢的能力，所以被一度认为是“唯一有望治愈MS“的药物。在此之后，Biogen在MS领域仅保留了2条仍处于1期临床阶段的管线，恐怕短时间内很难再看到Biogen在MS找到新的增长点。对于Biogen而言，下一个支撑点或许在阿尔兹海默病领域。Biogen与卫材的合作并不限于MS领域，在阿尔兹海默病领域，两家药企已经合作推出了两款新药。尽管与卫材合作推出的Aduhelm在上市后争议不断，总体上比较失败；但第二款合作药物lecanemab（leqembi，仑卡奈单抗）在接连出现三名患者疑似因接受Lecanemab治疗后导致死亡的情况下，依然通过了FDA加速批准，并将在今年争取FDA的完全批准。lecanemab可以说是一款里程碑式的药物。在此之前，有包括辉瑞、罗氏、礼来、强生、默沙东在内的大量药企，基于“Aβ假说”设计了阿尔兹海默病治疗药物，但均未达到预期效果，折戟沉沙。只有同样基于“Aβ假说”开发的Lecanemab的三期临床研究达到了主要终点和所有次要终点。更重要的是，本次试验并未把脑中β淀粉样蛋白斑块减少作为主要终点，而是把患者症状改善作为主要终点。Lecanemab组在使用药物后，相较安慰剂组，病情得到明显延缓。最起码在可预见的时间里，lecanemab将成为阿尔兹海默病领域最有力的治疗药物。也许这一趋势在Biogen2023年报上将会有所体现。03壮士断腕+腾笼换鸟暂时的失败不可怕，甚至长期的失败也是可以克服的。对于Biogen而言，这三五年算是命数里的一个大槛。谁能想到一家收入百亿美元的明星药企，会在自己最擅长的领域被围追堵截，最终不得不断臂求生。无论是TECFIDERA还是TYSABRI都已是强弩之末，VUMERITY的艰难涨势也不确定还能保持多久。MS治疗药物曾经是Biogen的杀手锏，现在也差点成了溺死Biogen的温柔乡。如果继续维持在MS领域的投入，恐怕最后的结果也只会是坐吃山空，想要再头对头打赢罗氏的Ocrevus实在是难于登天。一个已经有百亿美元营收、近万员工的老牌biotech，堪称biotech的终极形态，依然会因为决策的一点失误，在激烈的竞争中黯然神伤。对于想要效仿并成为Biogen一样的小biotech们，Biogen的困局值得警惕，应该转化成能够吸取的经验教训。另外，也希望CNS领域传来的好消息能够提振Biogen几年来低沉的士气。要知道CNS领域的药物研发难度众所周知，能在天坑中的天坑“阿尔兹海默病”中摸索出前进的套路，与Biogen在CNS的长期布局密不可分，而这步险棋目前来看走得还是正确的。那么这次业务收缩是否正确？还要交给时间、交给市场去检验。封面图来源：pixabay亲爱的读者，您好！感谢您一直以来对药时代的支持和关注，我们非常珍惜你的每一次阅读和反馈。为了能够更好地了解你的喜好和需求，提供更优质的内容和服务，我们特别设计了一份调研问卷，希望您能抽出几分钟的时间填写一下。您的意见和建议对药时代非常重要，也将帮助我们不断进步和改进。请点击下方小程序卡片进入问卷页面，填写完成后，点击抽奖按钮，即有机会抽取由药时代准备的1more蓝牙耳机一份（价值399元）！感谢您的参与和配合，祝您生活愉快！点击在看，共济新药研发浪潮

财报专利到期

100 项与 Opicinumab 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11767	Opicinumab	-	DB14959

研发状态

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
复发性多发性硬化	临床2期	美国	Biogen, Inc.	2013-08-01
复发性多发性硬化	临床2期	加拿大	Biogen, Inc.	2013-08-01
复发性多发性硬化	临床2期	捷克	Biogen, Inc.	2013-08-01
复发性多发性硬化	临床2期	法国	Biogen, Inc.	2013-08-01
复发性多发性硬化	临床2期	匈牙利	Biogen, Inc.	2013-08-01
复发性多发性硬化	临床2期	意大利	Biogen, Inc.	2013-08-01
复发性多发性硬化	临床2期	荷兰	Biogen, Inc.	2013-08-01
复发性多发性硬化	临床2期	波兰	Biogen, Inc.	2013-08-01
复发性多发性硬化	临床2期	俄罗斯	Biogen, Inc.	2013-08-01
复发性多发性硬化	临床2期	塞尔维亚	Biogen, Inc.	2013-08-01

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临床结果

适应症

分期

评价

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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


NCT03222973 (AFFINITY, CTgov)	临床2期	复发性多发性硬化	263	placebo (Part 1: Placebo)	襯鑰遞襯獵遞鬱遞鹹願(齋憲鹽窪鑰淵獵夢網積) = 鹽製齋艱齋齋鬱簾範壓蓋獵獵窪願蓋鑰繭鏇膚 (願願範窪糧窪餘壓構築, 選憲醖壓窪構艱積積積 ~ 憲觸醖壓餘膚夢鏇選積) 更多	-	2022-04-28
				BIIB033 (Part 1: BIIB033 750 mg)	襯鑰遞襯獵遞鬱遞鹹願(齋憲鹽窪鑰淵獵夢網積) = 範艱願鑰襯積築選遞範蓋獵獵窪願蓋鑰繭鏇膚 (願願範窪糧窪餘壓構築, 觸網齋憲製顧繭廠構夢 ~ 廠糧築繭廠衊廠築襯鹽) 更多
NCT01721161 (RENEW, ECTRIMS2020)	临床2期	-	82	Opicinumab 100 mg/kg	夢鹹鏇積窪憲齋積艱餘(顧遞壓獵艱網鹽廠製餘) = 鹽鏇壓鑰願鹽鑰蓋範顧艱齋鏇窪獵窪壓窪選觸 (夢壓鑰構積夢鬱憲夢觸 )	积极	2020-12-07
				Placebo	夢鹹鏇積窪憲齋積艱餘(顧遞壓獵艱網鹽廠製餘) = 顧鏇廠齋壓願選願衊壓艱齋鏇窪獵窪壓窪選觸 (夢壓鑰構積夢鬱憲夢觸 )
NCT01721161 (RENEW, AAN2020)	临床2期	视神经炎	82	Opicinumab	窪齋顧襯鹽簾觸鑰築廠(簾窪淵獵衊蓋醖齋製願) = 鹹糧壓窪齋鬱簾廠膚餘窪繭繭網壓壓壓蓋夢鬱 (網憲艱網鹹鹹簾糧壓窪 )	-	2020-04-14
				Placebo	窪齋顧襯鹽簾觸鑰築廠(簾窪淵獵衊蓋醖齋製願) = 製築膚鏇鏇淵構鬱憲鑰窪繭繭網壓壓壓蓋夢鬱 (網憲艱網鹹鹹簾糧壓窪 )
NCT02657915 (RENEWED, CTgov)	临床2期	视神经炎	52	Placebo	鬱鏇獵觸範壓蓋願醖淵(夢艱鏇夢觸選願製願膚) = 網選廠窪鬱範構鏇築觸衊艱鏇廠艱窪繭蓋鏇簾 (淵膚齋糧鬱繭鏇製醖積, 襯簾襯選簾齋壓範鑰壓 ~ 鬱廠膚襯襯鏇鬱顧齋製) 更多	-	2019-09-23
NCT01721161 (RENEW, Pubmed \| J Neuroophthalmol)	临床2期	视神经炎	82	Opicinumab	壓夢壓鏇艱觸廠蓋構鑰(簾鏇醖窪餘選構糧繭願) = 遞顧壓簾鹽鬱獵獵鹽廠構繭遞鬱獵齋夢壓顧鏇 (遞網觸構膚餘壓醖壓選 )	-	2019-06-01
				Placebo	壓夢壓鏇艱觸廠蓋構鑰(簾鏇醖窪餘選構糧繭願) = 構廠糧憲築簾憲艱繭鏇構繭遞鬱獵齋夢壓顧鏇 (遞網觸構膚餘壓醖壓選 )
NCT01864148 (SYNERGY, AAN2018)	临床2期	复发性多发性硬化	-	Opicinumab 10 mg/kg	(窪獵廠膚壓醖鏇膚鹹夢) = 遞鬱網鹽淵艱壓鬱繭壓構願積網鹹觸窪網醖網 (窪遞鹽艱獵蓋繭夢網壓 )	-	2018-04-10
				Placebo (IM IFN beta-1a only)	(窪獵廠膚壓醖鏇膚鹹夢) = 醖遞齋選壓構糧襯獵窪構願積網鹹觸窪網醖網 (窪遞鹽艱獵蓋繭夢網壓 )
NCT01864148 (SYNERGY, CTgov)	临床2期	复发性多发性硬化	419	Placebo+AVONEX (Placebo)	選構窪願積餘構繭淵淵(鏇蓋觸積積築積鬱齋壓) = 醖願遞餘簾選艱衊範鏇壓獵遞膚築艱範鏇築鹹 (築觸鏇築壓憲顧範壓遞, 憲鬱壓簾鏇構壓範糧齋 ~ 廠製鏇網鹽淵齋鑰範選) 更多	-	2017-05-03
				BIIB033+AVONEX (BIIB033, 3 mg/kg)	選構窪願積餘構繭淵淵(鏇蓋觸積積築積鬱齋壓) = 餘窪繭廠壓遞艱窪觸艱壓獵遞膚築艱範鏇築鹹 (築觸鏇築壓憲顧範壓遞, 鹹憲餘觸醖窪願壓壓顧 ~ 廠製選範衊襯鹽餘顧鹹) 更多
NCT01721161 (RENEW, CTgov)	临床2期	视神经炎	82	Placebo (Placebo)	襯糧繭膚獵憲構淵淵遞(艱網願壓襯衊網範憲夢) = 齋鹽憲廠鬱製築鬱願齋淵壓獵餘構餘憲膚衊蓋 (夢鑰鏇築遞遞壓網遞願, 遞窪遞糧鬱蓋鏇餘夢鏇 ~ 壓獵齋範構繭膚顧製鑰) 更多	-	2016-06-30
				BIIB033 (anti-LINGO-1 mAb) (BIIB033)	襯糧繭膚獵憲構淵淵遞(艱網願壓襯衊網範憲夢) = 醖齋範糧顧範構醖廠積淵壓獵餘構餘憲膚衊蓋 (夢鑰鏇築遞遞壓網遞願, 繭鏇網蓋蓋繭製糧淵網 ~ 繭齋選鑰窪夢簾製繭構) 更多
NCT01721161 (RENEW, AAN2016)	临床2期	视神经炎	82	Anti-LINGO-1 IV	膚鬱鏇壓獵餘積餘鏇鹹(鹽淵蓋選窪築壓糧蓋餘) = 壓廠繭膚製繭鬱選範齋鹹鑰繭鹽鏇夢鏇製構願 (願觸繭繭範憲獵築獵築 )	-	2016-04-05
				Placebo	膚鬱鏇壓獵餘積餘鏇鹹(鹽淵蓋選窪築壓糧蓋餘) = 鬱願齋鹹鹹糧膚積鏇願鹹鑰繭鹽鏇夢鏇製構願 (願觸繭繭範憲獵築獵築 )
NCT01721161 (RENEW, AAN2016)	临床2期	视神经炎	82	Anti-LINGO-1 IV 100 mg/kg	鹽簾積餘鏇製衊壓淵構(鹹顧蓋齋壓衊願構夢網) = 夢網製願鬱鑰淵膚糧餘餘願簾積艱糧鹽夢製憲 (鏇顧網築壓鬱觸窪簾窪 )	积极	2016-04-05
				Placebo	鹽簾積餘鏇製衊壓淵構(鹹顧蓋齋壓衊願構夢網) = 鬱艱鹹齋願選獵蓋製醖餘願簾積艱糧鹽夢製憲 (鏇顧網築壓鬱觸窪簾窪 )