更新于：2024-09-07

Cinpanemab

辛帕奈单抗

更新于：2024-09-07

概要

概要

基本信息

药物类型

单克隆抗体

别名

Cinpanemab (USAN)、Immunoglobulin g1, anti-(human .alpha.-synuclein) (human monoclonal biib054 .gamma.1-chain), disulfide with human monoclonal biib054 .kappa.-chain, dimer、Immunoglobulin g1-lambda, anti-(homo sapiens alpha-synuclein)humanized monoclonal antibody.gamma.1 heavy chain (1-442) (homo sapiens vh (ighv3-25*03 (86%) (ighd)-ighj2*01) (8.10.4) (1-113)-homo sapiens ighg1*03 (ch3(k107>del(443))) (114-442)) (216-213')-

+ [3]

靶点

α-synuclein

作用机制

α-synuclein抑制剂(α-突触核蛋白抑制剂)

治疗领域

神经系统疾病内分泌与代谢疾病

在研适应症-

非在研适应症

帕金森病

原研机构

Neurimmune Holding AG

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 315620518H

来源: *****

Sequence Code 315620519L

来源: *****

关联

项与辛帕奈单抗相关的临床试验

NCT03716570 / Terminated临床1期

A Multicenter, Blinded, Placebo-Controlled, Randomized, Single and Multiple-Ascending Dose Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BIIB054 in Japanese Subjects With Parkinson's Disease

The primary objective of this study is to evaluate the safety and tolerability of a range of single and 13 repeated doses of BIIB054, administered as intravenous (IV) infusion, in Japanese participants with Parkinson's disease (PD). The secondary objectives are to evaluate the immunogenicity, and serum pharmacokinetics (PK) profile of BIIB054 after single and multiple dose administration.

开始日期2019-03-12

申办/合作机构

Biogen, Inc.

NCT03318523 / Terminated临床2期

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study, With an Active-Treatment Dose-Blinded Period, to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of BIIB054 in Subjects With Parkinson's Disease

The primary objective of the study is to evaluate the clinical efficacy of BIIB054 via dose response using the change from baseline in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Total Score.
The secondary objectives of the study are to evaluate the dose-related safety of BIIB054, to evaluate the clinical efficacy of BIIB054 via MDS-UPDRS total score, to assess the pharmacokinetic (PK) profile of BIIB054, to evaluate the clinical efficacy of BIIB054 based on MDS-UPDRS subparts, to evaluate the pharmacodynamic effects of BIIB054 on the integrity of nigrostriatal dopaminergic nerve terminals and to evaluate the immunogenicity of BIIB054.

开始日期2018-01-10

申办/合作机构

Biogen, Inc.

NCT02459886 / Completed临床1期

A Phase 1 Randomized, Double-Blinded, Placebo-Controlled Single-Ascending Dose Study of the Safety, Tolerability, and Pharmacokinetics of BIIB054 in Healthy Subjects and Subjects With Early Parkinson's Disease

The primary objective of the study is to evaluate the safety and tolerability of a range of single BIIB054 doses, administered as a single intravenous (IV) infusion, in healthy participants and participants with early Parkinson's disease (PD). Secondary objectives of the study are to assess the serum pharmacokinetics (PK) profile of BIIB054 after single-dose administration and to evaluate the immunogenicity of BIIB054 after single-dose administration.

开始日期2015-07-01

申办/合作机构

Biogen, Inc.

100 项与辛帕奈单抗相关的临床结果

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100 项与辛帕奈单抗相关的转化医学

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100 项与辛帕奈单抗相关的专利（医药）

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项与辛帕奈单抗相关的文献（医药）

2024-03-01·Neural regeneration research

Single-neuron neurodegeneration as a degenerative model for Parkinson's disease.

Review

作者: Huenchuguala, Sandro ; Segura-Aguilar, Juan

The positive effect of levodopa in the treatment of Parkinson's disease, although it is limited in time and has severe side effects, has encouraged the scientific community to look for new drugs that can stop the neurodegenerative process or even regenerate the neuromelanin-containing dopaminergic nigrostriatal neurons. Successful preclinical studies with coenzyme Q10, mitoquinone, isradipine, nilotinib, TCH346, neurturin, zonisamide, deferiprone, prasinezumab, and cinpanemab prompted clinical trials. However, these failed and after more than 50 years levodopa continues to be the key drug in the treatment of the disease, despite its severe side effects after 4-6 years of chronic treatment. The lack of translated successful results obtained in preclinical investigations based on the use of neurotoxins that do not exist in the human body as new drugs for Parkinson's disease treatment is a big problem. In our opinion, the cause of these failures lies in the experimental animal models involving neurotoxins that do not exist in the human body, such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 6-hydroxydopamine, that induce a very fast, massive and expansive neurodegenerative process, which contrasts with the extremely slow one of neuromelanin-containing dopaminergic neurons. The exceedingly slow progress of the neurodegenerative process of the nigrostriatal neurons in idiopathic Parkinson's patients is due to (i) a degenerative model in which the neurotoxic effect of an endogenous neurotoxin affects a single neuron, (ii) a neurotoxic event that is not expansive and (iii) the fact that the neurotoxin that triggers the neurodegenerative process is produced inside the neuromelanin-containing dopaminergic neurons. The endogenous neurotoxin that fits this degenerative model involving one single neuron at a time is aminochrome, since it (i) is generated within neuromelanin-containing dopaminergic neurons, (ii) does not cause an expansive neurotoxic effect and (iii) triggers all the mechanisms involved in the neurodegenerative process of the nigrostriatal neurons in idiopathic Parkinson's disease. In conclusion, based on the hypothesis that the neurodegenerative process of idiopathic Parkinson's disease corresponds to a single-neuron neurodegeneration model, we must search for molecules that increase the expression of the neuroprotective enzymes DT-diaphorase and glutathione transferase M2-2. It has been observed that the activation of the Kelch-like ECH-associated protein 1/nuclear factor (erythroid-derived 2)-like 2 pathway is associated with the transcriptional activation of the DT-diaphorase and glutathione transferase genes.

2022-12-16·Journal of Parkinson's disease

Prasinezumab and Cinpanemab – The Perspective of a Person with Parkinson’s

Article

作者: McFarthing, Kevin

2022-08-04·The New England journal of medicine1区 · 医学

Trial of Cinpanemab in Early Parkinson’s Disease

1区 · 医学

Article

作者: Tanner, Caroline M. ; Inra, Jennifer ; Giladi, Nir ; Yang, Minhua ; Postuma, Ronald B. ; Macklin, Eric A. ; Mollenhauer, Brit ; Budd Haeberlein, Samantha ; Dam, Tien ; Fernandez, Hubert H. ; Stocchi, Fabrizio ; Fraser, Kyle ; Xiao, James ; Simon, David K. ; Rascol, Olivier ; Poewe, Werner ; Brooks, David J. ; Tolosa, Eduardo ; Hutchison, R. Matthew ; Cedarbaum, Jesse M. ; Lang, Anthony E. ; Siderowf, Andrew D. ; Fox, Tara ; Evans, Karleyton C. ; Sapir, Inbal ; Graham, Danielle L.

BACKGROUND:

Aggregated α-synuclein plays an important role in Parkinson's disease pathogenesis. Cinpanemab, a human-derived monoclonal antibody that binds to α-synuclein, is being evaluated as a disease-modifying treatment for Parkinson's disease.

METHODS:

In a 52-week, multicenter, double-blind, phase 2 trial, we randomly assigned, in a 2:1:2:2 ratio, participants with early Parkinson's disease to receive intravenous infusions of placebo (control) or cinpanemab at a dose of 250 mg, 1250 mg, or 3500 mg every 4 weeks, followed by an active-treatment dose-blinded extension period for up to 112 weeks. The primary end points were the changes from baseline in the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) total score (range, 0 to 236, with higher scores indicating worse performance) at weeks 52 and 72. Secondary end points included MDS-UPDRS subscale scores and striatal binding as assessed on dopamine transporter single-photon-emission computed tomography (DaT-SPECT).

RESULTS:

Of the 357 enrolled participants, 100 were assigned to the control group, 55 to the 250-mg cinpanemab group, 102 to the 1250-mg group, and 100 to the 3500-mg group. The trial was stopped after the week 72 interim analysis owing to lack of efficacy. The change to week 52 in the MDS-UPDRS score was 10.8 points in the control group, 10.5 points in the 250-mg group, 11.3 points in the 1250-mg group, and 10.9 points in the 3500-mg group (adjusted mean difference vs. control, -0.3 points [95% confidence interval {CI}, -4.9 to 4.3], P = 0.90; 0.5 points [95% CI, -3.3 to 4.3], P = 0.80; and 0.1 point [95% CI, -3.8 to 4.0], P = 0.97, respectively). The adjusted mean difference at 72 weeks between participants who received cinpanemab through 72 weeks and the pooled group of those who started cinpanemab at 52 weeks was -0.9 points (95% CI, -5.6 to 3.8) for the 250-mg dose, 0.6 points (95% CI, -3.3 to 4.4) for the 1250-mg dose, and -0.8 points (95% CI, -4.6 to 3.0) for the 3500-mg dose. Results for secondary end points were similar to those for the primary end points. DaT-SPECT imaging at week 52 showed no differences between the control group and any cinpanemab group. The most common adverse events with cinpanemab were headache, nasopharyngitis, and falls.

CONCLUSIONS:

In participants with early Parkinson's disease, the effects of cinpanemab on clinical measures of disease progression and changes in DaT-SPECT imaging did not differ from those of placebo over a 52-week period. (Funded by Biogen; SPARK ClinicalTrials.gov number, NCT03318523.).

项与辛帕奈单抗相关的新闻（医药）

2024-07-10

·生物制药小编

美国总统要是得了帕金森，该怎么用新药治

7月6日，《纽约邮报》爆料，著名帕金森症专家坎纳德自2023年8月以来，已经8次进入白宫会见美国总统拜登的私人医生奥康纳。联系拜登此前在辩论的表现，外界普遍怀疑拜登可能患有帕金森早期症状。虽然并没有实锤，但是这一问题仍然展现了帕金森这一尚未满足的临床需求。而在生物制药行业内，为患者提供“尚未满足的临床需求”是生物制药行业近年来的价值导向。那现在正好有一位身处华盛顿特区，白宫，亟需治疗的帕金森前期患者，这位患者约80岁，性别为生理男性。这位患者可能相对较为忙碌，对治疗的便捷性，对于副作用的要求，临床试验的成功率，对治疗的安全性要求都很高，可能期望获得一次服用长时间稳定有效的治疗手段，让我们看看有哪些帕金森新药可能适合他。本文纯属虚构，如有雷同，纯属巧合。传统帕金森疗法的缺点和新药排除标准帕金森病是一种常见的中老年神经系统退行性疾病，病理改变主要以黑质多巴胺神经元丢失以及α-突触核蛋白聚集体为主，而常见药物左旋多巴虽然能够通过补充脑内的多巴胺水平来帮助患者缓解运动障碍等症状，但无法做到根治，可能随着药效波动伴有明显副作用（例如：开关现象），且并不能逆转疾病的进展。而在6月末，拜登在辩论中多次出现的“僵住”现象，表现为突然停止动作或言语，这就和帕金森症开关现象中的关期症状有一定的相似性。考虑到该患者对于临床试验成功的要求较高，因此我们这里排除了一部分近期临床上表现可能相对没有那么好的新药研究，选用相对来说，更加有希望的帕金森疗法。例如一些已经成功的II期临床，又例如一些在某些次要终点中展现出潜在优势的疗法。可能被排除的帕金森疗法 α突触核蛋白（α-syn）抗体疗法在近年来表现不佳，临床进度靠前的玩家进展不利，虽然靶向的是α-syn不同的位点，但是殊途同归的都面临着临床失败。两大巨头罗氏和渤健的α-syn抗体Prasinezumab和Cinpanemab均未达到临床终点。渤健已经彻底放弃，罗氏还想要依靠次要终点的运动症状评分改善为方向进行开发。艾伯维也放弃了该赛道，2022年4月时，艾伯维突然将α-syn抗体ABBV-0805权益退还给了合作方BioArctic。丹麦公司Lundbeck Inc和Genmab AS合作开发的Lu AF82422倒是仍然在稳步推进临床，近期已经在我国招募患者。境遇类似的还有LRRK2抑制剂，渤健/Denali此前开发的DNL151(BIIB122)的临床因为不明原因终止，且双方终止合作，这一领域虽然仍然有一部分相关药物开发，但仍然有待后续临床数据的公布，例如Neuron23的NEU-723。另外iPSC衍生多巴胺神经前体细胞疗法，目前来看拜耳已经在Bluerock上布局，Aspen Neuroscience已有布局，我国也有较为优秀的士泽生物已经开展相关临床，但是相关研究尚处于较早阶段。帕金森的AAV疗法似乎相对安全，但…… 虽然近年来AAV（腺相关病毒载体）相关基因治疗出现了一系列的临床事故，但是在帕金森中似乎相对安全。目前多巴胺合成的关键酶芳香酸脱羧酶(AADC)是AAV替代疗法的几个主要治疗手段之一，由于持续需要外源性左旋多巴，AADC-AAV的组合不适合作为独立治疗，倒是可以辅助传统的左旋多巴药物共同治疗，比较具有代表性的可能是VGN-R09b（天泽云泰），但是该疗法的目前开发对象并非老年人，而是针对AADC缺乏的儿童（原发性的帕金森）。另外Voyager Therapeutics的VY-AADC似乎已经放弃了在老年人中开发，这使得该类疗法不符合这位老年人的需求。另外一些开发手段则例如，神经胶质细胞源性神经营养因子（GDNF），肌肉来源的营养因子--Neurturin(NRTN)，谷氨酸脱羧酶（GAD），不过这些研究目前的临床结果尚不明朗，出现了一些相左的结果，可能暗示更细分的亚群，这可能有待未来探索。从mRNA机制入手的Buntanetap 近期较有希望的一家公司是Annovis Bio，该公司的管线Buntanetap（ANVS401）是一类多靶点小分子脂质抑制剂，能够通过与mRNA上的调控元件结合，抑制多种蛋白的合成。这些蛋白包括生成β淀粉样蛋白的淀粉样前体蛋白（APP）、tau蛋白和α突触核蛋白。目前该药物已经在III期临床中大获成功，公司2日股价暴涨76%，5日股价再度大涨37%。 GLP-1又跨界了？考虑到坎纳德所属的医院是马里兰州知名的总统医院——沃尔特里德军事医学中心（Walter Reed Medical Center）或许马里兰州本地的Biotech也能提供一些特别的思路。 Neuraly是马里兰州建立的新兴Biotech公司，而该公司的思路极为有趣，打算采用GLP-1R激动剂来针对帕金森。目前这一疗法在这一疗法本身被设计成能够穿透血脑屏障。在临床前已被证明可以通过结合神经退行性疾病(如PD)动物模型中上调的GLP-1R来抑制小胶质细胞的病理激活。目前NLY01已经证明了抑制神经炎症和防止神经元细胞死亡的能力，这也提供了一种潜在的首款能够减缓PD进展的疾病缓解疗法。当然同样的开发模式也适用于阿尔兹海默症，这里可以看到该公司围绕NLY01管线开设了两类适应症。总结总的来说，本文从一名患者入手简单介绍了帕金森新药治疗的一部分情况，也期望帕金森新药能够实现目前未满足的临床需求，解决更多患者的现实问题。

临床2期

2023-04-11

·CPHI制药在线

研发 | 世界帕金森日：浅谈帕金森病研究进展，多种新疗法值得期待

自1997年开始，每年的4月11日被定为"世界帕金森日"。今年4月11日是第27个世界帕金森病日，其主题是：关注心理健康，全面全程管理。帕金森病（PD）是一种以震颤、肌强直、动作迟缓、姿势平衡障碍为主要表现的中老年神经系统退行性疾病。PD病因尚不明确，年龄老化、生活环境、化学制剂、遗传等都有可能是其致病因素。目前较公认的学说是PD与纹状体内的多巴胺（DA）含量显著减少有关。DA合成减少使纹状体DA含量降低，黑质-纹状体通路多巴胺能与胆碱能神经功能平衡失调，胆碱能神经元活性相对增高，使锥体外系功能亢进，发生震颤性麻痹。据流行病学调查，我国PD患者人数约占全球半数左右，我国65岁以上老年人群PD患病率约为1.7%。预计到2030年，我国PD患者将达到490万（全球约870万）。药物治疗首当其冲当前，PD治疗包括药物治疗、手术治疗、运动疗法、心理疏导及照料护理等，其中药物治疗是PD的首选治疗方式，且是整个治疗过程中的主要治疗手段。根据作用机制的不同，传统抗PD药物主要包括六大类，详见下表。其中抗胆碱能药物是一类较早用于治疗PD患者震颤的药物，最常用的是苯海索。多巴胺替代药左旋多巴能减轻震颤，有效改运动迟缓与强直症状，是目前治疗PD最有效的口服药物。DR激动剂主要包括麦角类DR激动剂和非麦角类DR激动剂，其中麦角类DR激动剂可导致心脏瓣膜病变和肺胸膜纤维化，在国内外已很少使用，非麦角类DR激动剂适用于早发型PD患者的病程初期。COMT抑制剂主要作为左旋多巴的辅助性治疗，适用于有明显波动症状的重症PD患者，是目前欧美和国内治疗指南明确推荐的、辅助多巴胺治疗PD患者的一线药物。MAO-B抑制剂是PD一线治疗药物，用于早期PD的单药治疗或是晚期症状波动的辅助治疗。 PD药物分类、作用机制及代表药物市场格局上，国内外畅销PD药物品种结构差异明显。据悉，全球五大PD药物分别为罗替戈汀、雷沙吉兰、左旋卡比多巴、多巴丝肼以及屈昔多巴，而这五大品种几乎占据了89%的抗PD药物市场份额。而据中康CMH数据，我国PD药物品种集中度高，医院渠道和零售渠道中TOP2抗PD药物为多巴丝肼和普拉克索，而这两个品种占据了超六成的市场份额。然而，上述PD治疗手段和药物只能改善PD症状，不能阻止病情发展，更无法治愈PD。目前，临床上亟待开发PD治疗新方法，来帮助每一位深受PD折磨的患者。新靶点、新疗法不断涌现随着对PD发病机制研究的深入，以及新疗法的兴起，目前已有多款PD新药进入临床试验阶段，详见下表。其中IPX203、ABBV-951等进展较快，已在美国递交NDA，不过ABBV-951惨遭FDA拒批。 • IPX203是一种新型的口服卡比多巴/左旋多巴（CD/LD）缓释胶囊，含有速释和缓释颗粒，以及粘膜附着聚合物，可提供快速吸收并使左旋多巴吸收最大化。已公布的3期临床试验结果显示：与活性对照组相比，IPX-203使PD患者得到具有统计学显著性的症状改善。2022年12月，FDA受理IPX203治疗PD的NDA。 • ABBV-951是左旋多巴和卡比多巴的前体药物，具有较高水溶性，可以通过一个连接到皮下的泵实现持续24小时皮下输注给药，从而使体内的左旋多巴和卡比多巴浓度在24h内保持稳定，改善晚期帕金森病患者的药效波动。已公布的3期临床试验M15-736的结果显示：ABBV-951与口服立即释放的左旋多巴/卡比多巴相比，在控制晚期帕金森病患者运动症状波动方面具有更好的效力。2022年5月，艾伯维向FDA递交ABBV-951治疗晚期PD患者运动症状波动的NDA。遗憾的是，今年 2月，ABBV-951惨遭FDA拒批。FDA在CRL中要求艾伯维提供ABBV-951设备（泵）的额外信息，但不需要再额外做与该药相关的疗效和安全性试验。 • LY03003是全球首个长期产生持续多巴胺能刺激（CDS）的药物，也是绿叶制药基于其微球技术平台开发的重磅新药之一。LY03003采用一周一次肌肉注射给药，有望昼夜持续改善患者症状，提高生活质量。LY03003在人体内的稳定释放，能够改善早期和进展期PD患者的运动和非运动症状，减少PD患者的"开关"现象和运动并发症的出现，长期应用有望推迟运动并发症的发生。LY03003在国内开展的治疗早期PD的3期临床试验结果显示：与安慰剂组相比，LY03003组统一帕金森病评分量表（UPDRS）Ⅱ+Ⅲ评分较基线显著改善，两组差异具有统计学意义。 • BIIB122（又称DNL151）是Denali Therapeutics开发一款小分子LRRK2激酶抑制剂（LRRK2错义突变是常染色体显性遗传PD最常见的原因，以LRRK2为靶点的疗法被认为是PD的潜力疗法），目前正在海外开展治疗PD的3期临床试验。在健康志愿者中开展的1期研究和在PD患者中开展的1b期研究结果显示：通过pS935 LRRK2和pT73 Rab10测量，BIIB122治疗参与了靶点调控和下游信号通路，并且实现了尿液中溶酶体脂质BMP（溶酶体功能的生物标志物）水平的剂量依赖性减少。2020年8月，渤健与Denali Therapeutics达成一项超10亿美元的合作，获得合作开发和共同商业化BIIB122的权益。 • AM006是一款新型非麦角类多巴胺受体激动剂，有潜力通过对多巴胺受体的高亲和力和刺激纹状体多巴胺受体，来改善PD。早期研究显示，AM006在健康受试者和早期PD患者中具有良好的安全性和药代动力学特征，且用药后导致的睡眠障碍、嗜睡等不良反应发生率明显较低。2020 年 10 月，AffaMed Pharmaceutical与 Kissei Pharmaceutical 签订独家许可协议，获得AM006在大中华区（中国大陆、中国台湾、中国香港和中国澳门）和东南亚地区（新加坡、马来西亚、泰国、印度尼西亚、越南和菲律宾）的开发和商业化授权。 • mesdopetam（IRL790）是一种新型多巴胺D3受体拮抗剂，开发用于PD患者。已完成的1b期和2a期临床项目数据显示：在正经历左旋多巴诱导的运动障碍（LID）的PD患者中，mesdopetam治疗使临床相关终点有很大的改善，减少了PD患者经历运动障碍的时间、延长了患者的"ON-Time（开启期）"。2021年7月，益普生与IRLAB Therapeutics 签订了一项许可协议，获得mesdopetam（IRL790）的独家全球开发和商业化权利。 • VG081821AC是一种非多巴胺类的高选择性的腺苷A2A受体拮抗剂，可望作为单药用于治疗早中期PD，或与低剂量的左旋多巴联用用于治疗中晚期PD。同时，由于对神经细胞具有一定保护和改善作用，VG081821AC还有望能够延缓帕金森病的发展进程。2023年4月，VG081821AC治疗早中期PD的2期临床试验启动。 • BIIB094是LRRK2基因的反义寡核苷酸（ASO）药物，通过阻断LRRK2突变基因蛋白质翻译，从而控制疾病。 • DA01是一种多能干细胞衍生的多巴胺能神经元，是同类首个细胞疗法，有潜力再生失去的功能，并可能改善和逆转PD，曾被FDA授予治疗PD的快速通道资格。目前，DA01正在进行治疗晚期PD的1期临床。整体来看，除了改良型新药（如LY03003、ABBV-951和IPX203），在研PD药物出现了不少新靶点、新疗法。在研PD药物新靶点包括富亮氨酸重复激酶2（LRRK2）、α-突触核蛋白靶点（α-syn）。其中α-syn异常聚集形成的路易小体是PD患者的病理学特点之一，是第一个被确定与PD相关的有基因突变的蛋白，减少其产生能够减缓或阻止疾病进展，在研药物包括Cinpanemab和Prasinezumab。在研PD新疗法包括基因疗法和细胞疗法，其中PD基因疗法目前要通过增加多巴胺合成、调节神经营养因子表达和促进神经调节弥补基底节多巴胺信号缺失，挽救PD运动性症状。而PD细胞疗法主要是向大脑中移植新的神经细胞，以替代原有损伤或凋亡的细胞并产生新的多巴胺，利用真正的多巴胺能神经元，重新建立人脑受影响区域的神经支配，从而逆转退化过程，潜在恢复患者运动功能。治疗PD的干细胞来源多样，如胚胎干细胞（ESCs）、神经干细胞（NSCs）和间充质干细胞（MSCs）等。总结帕金森病(PD)是继阿尔茨海默病(AD)后人类的第二大神经退行性疾病，据不完全统计全球大约有1000万PD患者。而且，随着全球老龄化的加剧，罹患PD的人数还有可能进一步增加。基于庞大的患者体量和治疗需求，2020年全球PD用药市场规模达45.64亿美元，预计2026年将以4.68%的复合年均增长率增至59.34亿美元。然而，PD现有治疗手段疗效有限，只能在一定程度上改善PD症状，并不能逆转PD进程。目前，PD领域急需更加有效的治疗药物和方法。值得期待的是，国内外药企已开发出多款在研PD新疗法。期待这些药物可以早日通过监管批准，造福广大PD患者，改善当前PD治疗困境。内容来源于网络，如有侵权，请联系删除。

2021-02-04

·BioSpace

Biogen Ditches Parkinson's Drug After Phase II Study Fails to Show Benefit

Photo courtesy of Biogen. Biogen announced Wednesday morning in its annual results and earnings presentation that its Phase II SPARK study of cinpanemab, a candidate drug for Parkinson’s disease, missed its primary and secondary endpoints. As the therapy “did not achieve proof-of-concept” and failed to provide benefit in this study, the development of the drug has been discontinued. The Phase II SPARK study examined the ability of cinpanemab, an anti-alpha synuclein (syn) monoclonal antibody, to reduce a measure of impairment and disability compared with placebo. Biogen was hopeful that the drug could successfully compete with Roche and Prothena’s syn therapy prasinezumab. “Although we made this determination in February 2021, it was based on conditions that existed as of December 31, 2020,” the Biogen statement said. “As a result, we recognized an impairment charge of approximately $75.4 million during the fourth quarter of 2020 to reduce the fair value of the related in-process research and development (IPR&D) intangible asset to zero.” The company added that it had adjusted the value of its contingent consideration obligation related to the drug, leading to a gain of $51 million in the fourth quarter of last year. Biogen’s cinpanemab was previously acquired from Neurimmune in 2016 and entered early-stage trials for Parkinson’s disease. In 2018, Biogen presented an overview of the design of the SPARK Phase II study, which at the time is the most advanced program in the company’s Parkinson’s disease pipeline. As Biogen tosses out cinpanemab, the company will switch focus to its Alzheimer’s disease drug aducanumab, co-developed with Tokyo-based Eisai. In late January, the U.S. Food and Drug Administration extended the review period for the companies’ Biologic License Application (BLA) for the therapy, which has been shrouded in controversy since its inception. The FDA’s decision on the drug application was expected March 7, but the delay will place the decision on the agency’s shoulders on June 7. “We are committed to working with the FDA as it completes its review of the aducanumab application,” Biogen’s Chief Executive Offer Michel Vounatsos said in a statement. “We want to thank the FDA for its continued diligence during the review.” Both Biogen and Eisai announced in March 2019 that they were discontinuing their global Phase III clinical trials ENGAGE and EMERGE, both of which were studying aducanumab in patients with mild cognitive impairment for Alzheimer’s and mild Alzheimer’s dementia. In addition, the companies said they were discontinuing their EVOLVE Phase II trial as well as the long-term extension of the PRIME Phase Ib study, after an independent data monitoring committee said these studies were unlikely to reach the primary endpoints. Fast-forward to October 2019, Biogen and Eisai said they still planned to seek regulatory approval for aducanumab, as the Phase III EMERGE trial did indeed meet its primary endpoint of significant reduction in clinical decline. The findings from this study were presented by Biogen at a conference in December, but the overall data were met with some outside skepticism. Despite this skepticism, the data appeared robust enough for the companies to file for a BLA. “Alzheimer’s disease remains one of the greatest public health challenges of our time,” said Vounatsos at the time. “The aducanumab BLA is the first filing for FDA approval of a treatment that addresses the clinical decline associated with this devastating condition, as well as the pathology of the disease. We are committed to driving progress for the Alzheimer’s disease community and look forward to the FDA’s review of our filing.” Most Read Today

合作抗体引进/卖出

100 项与辛帕奈单抗相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11467	-	-	DB16127

研发状态

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适应症	最高研发状态	国家/地区	公司	日期
帕金森病	临床2期	美国	Biogen, Inc.	2018-01-10
帕金森病	临床2期	奥地利	Biogen, Inc.	2018-01-10
帕金森病	临床2期	加拿大	Biogen, Inc.	2018-01-10
帕金森病	临床2期	法国	Biogen, Inc.	2018-01-10
帕金森病	临床2期	德国	Biogen, Inc.	2018-01-10
帕金森病	临床2期	以色列	Biogen, Inc.	2018-01-10
帕金森病	临床2期	意大利	Biogen, Inc.	2018-01-10
帕金森病	临床2期	西班牙	Biogen, Inc.	2018-01-10
帕金森病	临床2期	英国	Biogen, Inc.	2018-01-10

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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


NCT03318523 (SPARK, Pubmed \| Br Dent J)	临床2期	帕金森病（青年型、早发型）	357	Cinpanemab 250 mg	壓襯觸醖廠廠襯範醖顧(鑰製網夢壓壓糧衊鑰餘) = 醖鬱簾鬱網願構膚醖繭鑰製網夢蓋蓋築製鑰糧 (遞艱淵鏇鬱網築觸淵觸 )	不佳	2022-08-04
				Cinpanemab 1250 mg	壓襯觸醖廠廠襯範醖顧(鑰製網夢壓壓糧衊鑰餘) = 構鑰構鹹鬱獵醖蓋鹹鑰鑰製網夢蓋蓋築製鑰糧 (遞艱淵鏇鬱網築觸淵觸 )