Oveporexton(Oveporexton) - 药物靶点：OX2R_在研适应症：发作性睡病，猝倒症，过度嗜睡性障碍_专利_临床

概要

基本信息

药物类型

小分子化药

别名

TAK 861、TAK-861

靶点

OX2R

作用方式

激动剂

作用机制

OX2R激动剂(食欲素受体2激动剂)

治疗领域

神经系统疾病其他疾病

在研适应症

发作性睡病猝倒症过度嗜睡性障碍+ [1]

非在研适应症-

原研机构

Takeda Pharmaceutical Co., Ltd.

在研机构

Takeda Pharmaceutical Co., Ltd.Takeda Development Center Americas, Inc.

非在研机构-

权益机构-

最高研发阶段临床3期

首次获批日期-

最高研发阶段(中国)临床3期

特殊审评-

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结构/序列

分子式C23H25F5N2O4S

InChIKeyKVMGAIOTUIGROS-AZUAARDMSA-N

CAS号2460722-04-5

关联

8

项与 Oveporexton 相关的临床试验

CTR20243884

/ Recruiting临床3期

一项评价TAK-861在患有选定中枢性睡眠过度疾病的受试者中的安全性和耐受性的长期扩展研究

评价TAK-861的长期安全性和耐受性。

开始日期2025-01-14

申办/合作机构

Fisher Clinical Services GmbH

[+3]

NCT06505031

/ Completed临床3期

A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of TAK-861 for the Treatment of Narcolepsy With Cataplexy (Narcolepsy Type 1)

The main aim of this study is to learn how effective TAK-861 is in improving excessive sleepiness during the day (called excessive daytime sleepiness or EDS) after 3 months of treatment. Other aims are to learn how effective TAK-861 is in lowering the number of sudden, unexpected attacks of muscle weakness while staying conscious (cataplexy) in a week; to learn the effect TAK-861 has on participants' ability to maintain attention, participant's overall quality of life, the spectrum of narcolepsy symptoms and daily life functions; and to learn about the safety of TAK-861.

开始日期2024-11-07

申办/合作机构

Takeda Pharmaceutical Co., Ltd.

NCT06470828

/ Completed临床3期

A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of TAK-861 for the Treatment of Narcolepsy With Cataplexy (Narcolepsy Type 1)

The main aim of this study is to learn how effective TAK-861 is in improving excessive sleepiness during the day (called excessive daytime sleepiness or EDS) after 3 months of treatment. Other aims are to learn how effective TAK-861 is in lowering the number of sudden, unexpected attacks of muscle weakness while staying conscious (cataplexy) in a week; to learn the effect TAK-861 has on participants' ability to maintain attention, participant's overall quality of life, the spectrum of narcolepsy symptoms, and daily life functions; and to learn about the safety of TAK-861.

开始日期2024-07-02

申办/合作机构

Takeda Pharmaceutical Co., Ltd.

100 项与 Oveporexton 相关的临床结果

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100 项与 Oveporexton 相关的转化医学

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100 项与 Oveporexton 相关的专利（医药）

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3

项与 Oveporexton 相关的文献（医药）

2025-07-01·Nature Reviews Neurology

Benefits of oveporexton in narcolepsy type 1

Article

作者: Wood, Heather

2025-05-15·NEW ENGLAND JOURNAL OF MEDICINE

Oveporexton, an Oral Orexin Receptor 2–Selective Agonist, in Narcolepsy Type 1

Article

作者: Mignot, Emmanuel ; Sheikh, Sarah ; Khatami, Ramin ; Abraham, Anson ; Kadali, Harisha ; Dauvilliers, Yves ; von Hehn, Christian ; Taniguchi, Mitsutaka ; Tanaka, Shinichiro ; von Rosenstiel, Philipp ; Hang, Yaming ; Neuwirth, Rachel ; Plazzi, Giuseppe ; Swick, Todd J. ; del Río Villegas, Rafael ; Olsson, Tina ; Stukalin, Ellie ; Naylor, Melissa ; Wang, Hao ; Lamberton, Marta ; Cai, Alice ; Lammers, Gert Jan

BACKGROUND:

Narcolepsy type 1 is a disorder of hypersomnolence caused by a loss of orexin neurons, which results in low orexin levels in the brain.

METHODS:

In this phase 2, randomized, placebo-controlled trial, participants with narcolepsy type 1 received once- or twice-daily oveporexton (TAK-861), an oral orexin receptor 2-selective agonist, or placebo. The primary end point was the mean change from baseline to week 8 in average sleep latency (the time it takes to fall asleep) on the Maintenance of Wakefulness Test (MWT) (range, 0 to 40 minutes; normal, ≥20). Secondary end points included the change from baseline to week 8 in the Epworth Sleepiness Scale (ESS) total score (range, 0 to 24; normal, ≤10), the weekly cataplexy rate at week 8, and the occurrence of adverse events.

RESULTS:

A total of 90 participants received oveporexton (0.5 mg twice daily, 23 participants; 2 mg twice daily, 21 participants; 2 mg followed by 5 mg daily, 23 participants; and 7 mg once daily, 23 participants), and 22 received placebo. The mean changes from baseline to week 8 in average sleep latency on the MWT were 12.5, 23.5, 25.4, 15.0, and -1.2 minutes, respectively (adjusted P≤0.001 for all comparisons vs. placebo). The mean changes in the ESS total score at week 8 were -8.9, -13.8, -12.8, -11.3, and -2.5, respectively (adjusted P≤0.004 for all comparisons vs. placebo). The weekly incidence of cataplexy at week 8 was 4.24, 3.14, 2.48, 5.89, and 8.76, respectively (adjusted P<0.05 for 2 mg twice daily and 2 mg followed by 5 mg daily vs. placebo). The most common adverse events associated with oveporexton were insomnia (in 48% of the participants; most cases resolved within 1 week), urinary urgency (in 33%), and urinary frequency (in 32%), without any hepatotoxic effects.

CONCLUSIONS:

In this phase 2 trial involving participants with narcolepsy type 1, oveporexton significantly improved measures of wakefulness, sleepiness, and cataplexy over a period of 8 weeks. (Funded by Takeda Development Center Americas; TAK-861-2001 ClinicalTrials.gov number, NCT05687903.).

Scientific Reports

TAK-861, a potent, orally available orexin receptor 2-selective agonist, produces wakefulness in monkeys and improves narcolepsy-like phenotypes in mouse models

Article

作者: Kimura, Haruhide ; Yamada, Ryuji ; Koike, Tatsuki ; Monjo, Taku ; Hiyoshi, Tetsuaki ; Terada, Michiko ; Mitsukawa, Kayo ; Ando, Tatsuya ; Nakakariya, Masanori ; Kajita, Yuichi

Abstract:

Narcolepsy type 1 (NT1) is associated with severe loss of orexin neurons and characterized by symptoms including excessive daytime sleepiness and cataplexy. Current medications indicated for NT1 often show limited efficacy, not addressing the full spectrum of symptoms, demonstrating a need for novel drugs. We discovered a parenteral orexin receptor 2 (OX2R) agonist, danavorexton, and an orally available OX2R agonist, TAK-994; both improving NT1 phenotypes in mouse models and individuals with NT1. However, danavorexton has limited oral availability and TAK-994 has a risk of off-target liver toxicity. To avoid off-target-based adverse events, a highly potent molecule with low effective dose is preferred. Here, we show that a novel OX2R-selective agonist, TAK-861 [N-{(2S,3R)-4,4-Difluoro-1-(2-hydroxy-2-methylpropanoyl)-2-[(2,3′,5′-trifluoro[1,1′-biphenyl]-3-yl)methyl]pyrrolidin-3-yl}ethanesulfonamide], activates OX2R with a half-maximal effective concentration of 2.5 nM and promotes wakefulness at 1 mg/kg in mice and monkeys, suggesting ~ tenfold higher potency and lower effective dosage than TAK-994. Similar to TAK-994, TAK-861 substantially ameliorates wakefulness fragmentation and cataplexy-like episodes in orexin/ataxin-3 and orexin-tTA;TetO DTA mice (NT1 mouse models). Compared with modafinil, TAK-861 induces highly correlated brain-wide neuronal activation in orexin-tTA;TetO DTA mice, suggesting efficient wake-promoting effects. Thus, TAK-861 has potential as an effective treatment for individuals with hypersomnia disorders including narcolepsy, potentially with a favorable safety profile.

46

项与 Oveporexton 相关的新闻（医药）

2025-07-14

·医药笔记

全球首创：武田OX2R激动剂发作性睡病三期临床成功

▎Armstrong2025年7月14日，武田宣布全球首创OX2R激动剂Oveporexton（TAK-861）治疗发作性睡病（NT1）的两项关键注册性三期临床获得阳性数据，达到所有主要和次要终点。这两项三期临床FirstLight、RadiantLight在19个国家进行，治疗12周均达到主要终点和次要终点的显著改善，p＜0.001。武田将快速递交上市申请，以使发作性睡病患者尽快获益。武田预计Oveporexton的销售峰值降到20-30亿美元。Oveporexton为全球同类首创的OX2R激动剂，分子结构如下图所示。今年5月，Oveporexton治疗NT1的二期临床数据在新英格兰医学期刊发表。主要终点放米娜，与安慰剂相比，所有剂量组在清醒维持测试（MWT）中的平均入睡潜伏期显著增加。关键次要终点方面，与安慰剂相比，所有剂量组在Epworth嗜睡量表（ESS）评分以及每周猝倒发作频率（WCR）方面均有显著下降，并且这种改善在8周治疗期间持续。总结武田有多款食欲素靶点相关项目，此次TAK-861的成功意味着OX2R的临床POC，并有望达到20-30亿美元年销售峰值。Armstrong技术全梳理系列GPRC5D靶点全梳理；CD40靶点全梳理；CD47靶点全梳理；补体靶向药物技术全梳理；补体药物：眼科治疗的重要方向；Claudin 6靶点全梳理；Claudin 18.2靶点全梳理；靶点冷暖，行业自知；中国大分子新药研发格局；被炮轰的“me too”；佐剂百年史；胰岛素百年传奇；CUSBEA：风雨四十载；中国新药研发的焦虑；中国生物医药企业的研发竞争；中国双抗竞争格局；中国ADC竞争格局；中国双抗技术全梳理；中国ADC技术全梳理；Ambrx技术全梳理；Vir Biotech技术全梳理；Immune-Onc技术全梳理；亘喜生物技术全梳理；康哲药业技术全梳理；科济药业技术全梳理；恺佧生物技术全梳理；同宜医药技术全梳理；百奥赛图技术全梳理；腾盛博药技术全梳理；创胜集团技术全梳理；永泰生物技术全梳理；中国抗体技术全梳理；德琪医药技术全梳理；德琪医药技术全梳理2.0；和铂医药技术全梳理；荣昌生物技术全梳理；再鼎医药技术全梳理；药明生物技术全梳理；恒瑞医药技术全梳理；豪森药业技术全梳理；正大天晴技术全梳理；吉凯基因技术全梳理；基石药业技术全梳理；百济神州技术全梳理；百济神州技术全梳理第2版；信达生物技术全梳理；信达生物技术全梳理第2版；中山康方技术全梳理；复宏汉霖技术全梳理；先声药业技术全梳理；君实生物技术全梳理；嘉和生物技术全梳理；志道生物技术全梳理；道尔生物技术全梳理；尚健生物技术全梳理；康宁杰瑞技术全梳理；科望医药技术全梳理；岸迈生物技术全梳理；礼进生物技术全梳理；康桥资本技术全梳理；余国良的抗体药布局；荃信生物技术全梳理；安源医药技术全梳理；三生国健技术全梳理；仁会生物技术全梳理；乐普生物技术全梳理；同润生物技术全梳理；宜明昂科技术全梳理；派格生物技术全梳理；迈威生物技术全梳理；Momenta技术全梳理；NGM技术全梳理；普米斯生物技术全梳理；普米斯生物技术全梳理2.0；三叶草生物技术全梳理；贝达药业抗体药全梳理；泽璟制药抗体药全梳理；恒瑞医药抗体药全梳理；齐鲁制药抗体药全梳理；石药集团抗体药全梳理；豪森药业抗体药全梳理；华海药业抗体药全梳理；科伦药业抗体药全梳理；百奥泰技术全梳理；凡恩世技术全梳理。

临床2期抗体药物偶联物临床3期

2025-07-14

·药研网

销售峰值可达30亿美元！武田首创OX2R激动剂三期试验成功

7月14日，武田制药宣布，其同类首创口服食欲素受体2 （OX2R）选择性激动剂药物Oveporexton（TAK-861）在两项全球III期临床试验—FirstLight（TAK-861-3001）和RadiantLight（TAK-861-3002）中成功，在所有剂量下达成全部主要及次要终点，显著改善发作性嗜睡症1型（Narcolepsy Type 1, NT1）患者的多维度症状。这是全球首次在III期研究中确认Orexin（食欲素）受体激动剂的治疗有效性，标志着该机制的临床可行性正式得到验证。图源：武田官网NT1是一种因脑内食欲素神经元丧失所致的罕见神经系统疾病，常表现为过度嗜睡、猝倒（猝倒症/Cataplexy）以及REM睡眠紊乱。Oveporexton是一款口服、选择性靶向OX2R（食欲素受体2型）的激动剂，旨在恢复失衡的食欲素信号，从源头改善昼夜症状，提升患者清醒度、注意力维持能力及生活质量。两项III期研究共覆盖19个国家，在治疗第12周时，Oveporexton在所有剂量组对比安慰剂均显示高度统计学意义（p<0.001）的改善效果，涵盖客观唤醒能力、白天过度嗜睡、猝倒发作频率、注意力维持、生活功能等多个终点，大多数患者症状改善接近正常范围，为该药物树立了极具说服力的临床价值。安全性方面，Oveporexton表现良好，无严重治疗相关不良事件报告。最常见不良反应为失眠及泌尿频率增加。超过95%的研究完成者已进入长期扩展研究（LTE），进一步验证疗效与安全性持续性。武田研发总裁Andy Plump表示：“我们对Oveporexton展现出的广谱改善效果和快速推进节奏感到振奋。这不仅是武田在食欲素机制领域多年来积累的成果，更是对罕见神经疾病治疗范式的有力变革。”目前，武田正加速推进美国FDA及全球其他地区的上市申报，目标于2025财年内完成申报工作，并同步开展商业化准备。根据武田预测，Oveporexton的峰值销售额有望达到30亿美元。资料来源：武田尽管此次三期试验结果对2026财年财务预期无重大影响，但该管线被寄予厚望，或将成为Takeda未来增长的重要引擎。End声明：本公众号所有发文章(包括原创及转载文章)系出于传递更多信息之目的，且注明来源和作者。本公众号欢迎分享朋友圈或大群，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载/商务/投稿 | 联系微信15618157102（sum_Gmi）商务合作稿件征集点击了解详情往期回顾1港股创新药走出至暗时刻2License-out潮来袭：谁是下一个出海爆款?32025 ASCO热点速递 | 信达、荣昌、科伦集体登场!（附ADC/双/多抗最新进展一览表）

临床3期ASCO会议抗体药物偶联物引进/卖出医药出海

2025-07-14

·EndPoints

Takeda’s first-in-class narcolepsy drug succeeds in two registrational studies

Takeda’s oral orexin agonist has cleared a pair of Phase 3 trials in a sleep disorder, marking the first late-stage win for a drug class that Wall Street analysts say has multi-billion dollar potential. Oveporexton, as Takeda’s drug is known, achieved a “statistically significant improvement” over placebo on all endpoints in the FirstLight and RadiantLight studies, according to a Monday release . The trials enrolled more than 100 patients each with narcolepsy type 1, a chronic disorder that causes excessive daytime sleepiness, transient muscle weakness and sleep paralysis. The primary endpoint was change in the Maintenance of Wakefulness Test at 12 weeks. Unlike standard of care, oveporexton addresses the underlying cause of narcolepsy type 1. This disease develops when the brain loses neurons that make orexin, a neuropeptide that’s essential for maintaining wakefulness. Current treatment options include stimulant drugs and lifestyle changes. The twice-daily drug could reach $3 billion in peak sales for narcolepsy type 1, Jefferies analysts wrote on Monday, although they did not give a year for this. Takeda did not share detailed results in the release, but plans to do so at an upcoming medical meeting. The company said it will also submit the data to the FDA and other agencies. Oveporexton is part of a broader class of orexin agonists that have been drawing investor interest, including Alkermes’ ALKS 2680 and Centessa Pharmaceuticals’ ORX750, both of which are in Phase 2 development. Takeda is also advancing other candidates with the same mechanism, including TAK-360 for idiopathic hypersomnia.

临床2期临床3期临床结果

100 项与 Oveporexton 相关的药物交易

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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
发作性睡病	临床3期	捷克	Takeda Development Center Americas, Inc.	2024-10-08
发作性睡病	临床3期	丹麦	Takeda Development Center Americas, Inc.	2024-10-08
发作性睡病	临床3期	匈牙利	Takeda Development Center Americas, Inc.	2024-10-08
猝倒症	临床3期	美国	Takeda Pharmaceutical Co., Ltd.	2024-07-02
猝倒症	临床3期	日本	Takeda Pharmaceutical Co., Ltd.	2024-07-02
猝倒症	临床3期	加拿大	Takeda Pharmaceutical Co., Ltd.	2024-07-02
猝倒症	临床3期	法国	Takeda Pharmaceutical Co., Ltd.	2024-07-02
猝倒症	临床3期	德国	Takeda Pharmaceutical Co., Ltd.	2024-07-02
猝倒症	临床3期	意大利	Takeda Pharmaceutical Co., Ltd.	2024-07-02
猝倒症	临床3期	荷兰	Takeda Pharmaceutical Co., Ltd.	2024-07-02

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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


NCT05687903 (TAK-861-2001, BusinessWire \| Pubmed) 人工标引	临床2期	发作性睡病	112	oveporexton twice-daily 0.5/0.5 mg	窪窪廠範衊憲鏇壓願夢(齋網築衊願繭窪憲艱餘) = 鹹獵網鏇獵衊衊鑰壓獵壓襯襯衊顧鹹繭鏇鏇鏇 (齋觸衊壓醖糧範願獵願 ) 更多	积极	2025-05-14
				oveporexton twice-daily 2/2 mg	窪窪廠範衊憲鏇壓願夢(齋網築衊願繭窪憲艱餘) = 繭遞齋鏇鑰膚網繭構齋壓襯襯衊顧鹹繭鏇鏇鏇 (齋觸衊壓醖糧範願獵願 ) 更多
NCT05687903 (P12-4.002, AAN2025)	临床2期	发作性睡病 low cerebrospinal fluid orexin levels	112	TAK-861 0.5mg BID	繭壓淵鏇繭鏇壓築範衊(窪憲網齋繭壓積簾鬱艱) = 衊鹹鑰構憲艱簾範襯鬱糧壓簾鹽觸鬱築觸選衊 (鏇膚顧顧網鹹憲憲齋廠 )	积极	2025-04-07
				TAK-861 2mg BID	繭壓淵鏇繭鏇壓築範衊(窪憲網齋繭壓積簾鬱艱) = 蓋窪襯憲蓋鏇膚餘壓餘糧壓簾鹽觸鬱築觸選衊 (鏇膚顧顧網鹹憲憲齋廠 )
NCT05687916 (CTgov)	临床2期	发作性睡病	71	Placebo (Placebo)	鹽襯壓憲鬱壓夢壓鏇鹽(鏇獵壓鏇繭廠膚顧築遞) = 醖顧獵糧餘憲範憲網廠憲築衊築廠壓構壓淵鏇 (鬱膚衊衊憲顧淵觸夢襯, 2.246) 更多	-	2025-01-09
				TAK-861 (TAK-861 2 mg and 5 mg)	鹽襯壓憲鬱壓夢壓鏇鹽(鏇獵壓鏇繭廠膚顧築遞) = 窪製願顧構壓鹹糧獵廠憲築衊築廠壓構壓淵鏇 (鬱膚衊衊憲顧淵觸夢襯, 2.300) 更多
NCT05687903 (TAK-861-2001 \| P12-4.002, CTgov)	临床2期	发作性睡病	112	Placebo (Placebo)	積廠願艱廠構構構淵憲(觸衊遞獵築壓製鬱襯遞) = 鏇鬱築淵艱繭願願憲憲憲網襯簾憲窪壓鹹繭願 (選鹽網艱構淵鏇簾獵夢, 2.061) 更多	-	2025-01-09
				TAK-861 (TAK-861 0.5 mg BID)	積廠願艱廠構構構淵憲(觸衊遞獵築壓製鬱襯遞) = 醖願壓衊蓋鹽膚齋襯壓憲網襯簾憲窪壓鹹繭願 (選鹽網艱構淵鏇簾獵夢, 2.128) 更多
NCT05687903 (TAK-861-2001, NEWS) 人工标引	临床2期	发作性睡病	112	TAK-861	醖艱簾蓋蓋廠選窪蓋淵(願築鹽糧鏇繭膚鏇構襯) = The primary endpoint demonstrated statistically significant and clinically meaningful increased sleep latency on the Maintenance of Wakefulness Test (MWT) versus placebo across all doses (LS mean difference versus placebo all p ≤0.001). Improvements were sustained over 8 weeks. Mean sleep latency ranged from 16.5 minutes for the lowest 0.5mg/0.5mg dose up to 30.7 minutes for the 2mg/5mg dose, compared to just 7 minutes for placebo. 夢廠構襯蓋製艱壓襯顧 (齋製繭顧鑰鹹鏇蓋艱壓 ) 更多	积极	2024-06-03
				placebo
WSC2023	N/A	日夜节律睡眠障碍	-	TAK-861 high-dose (HD)	夢簾繭願廠憲衊積衊遞(鬱糧選積製蓋鹹蓋衊積) = reported by 3 (27.3%) subjects on TAK‑861 HD 淵鹹鑰觸憲糧鬱艱鹹繭 (廠齋窪簾鏇醖鏇鏇繭糧 )	-	2023-10-23
				TAK-861 low-dose (LD)