Camlipixant(Camlipixant) - 药物靶点：P2X3 receptor_在研适应症：不明原因的慢性咳嗽，难治性慢性咳嗽，咳嗽_专利_临床

概要

基本信息

药物类型

小分子化药

别名

AZ-13410937、AZ13410937、BLU 5937

+ [3]

靶点

P2X3 receptor

作用方式

拮抗剂

作用机制

P2X3 receptor拮抗剂(嘌呤P2X3受体拮抗剂)

治疗领域

在研适应症

非在研适应症

原研机构

在研机构

Neomed InstituteBELLUS Health Cough, Inc.

非在研机构-

权益机构

BELLUS Health, Inc.

GSK Plc

Neomed Institute

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C23H24F2N4O4

InChIKeySEHLMRJSQFAPCJ-HNNXBMFYSA-N

CAS号1621164-74-6

关联

15

项与 Camlipixant 相关的临床试验

NCT06497517

/ Completed临床1期

A Phase 1, Single Center, Single Dose, Open-Label, Randomized, 2-Way Crossover Study to Investigate the Food Effect on the Pharmacokinetics of Camlipixant in Healthy Male and Female Participants

This study is a single center, single dose, open-label, randomly assigned 2-way crossover study. The study will investigate the food effect on the pharmacokinetics of Camlipixant (GSK5464714) in healthy male and female participants. Eligible participants will be randomized to pre-defined sequences. There will be a washout of minimum 7 days between each dose of treatment period.

开始日期2024-07-09

申办/合作机构

BELLUS Health, Inc.

CTR20240965

/ Recruiting临床3期

一项在难治性或不明原因慢性咳嗽成人受试者中进行BLU-5937开放性扩展治疗的III期、24周、随机、疗效和安全性研究

主要目的：评估BLU-5937与安慰剂相比在基线24小时咳嗽频率≥8次咳嗽/小时的RCC（包括不明原因的慢性咳嗽）成人患者中对第24周时24小时咳嗽频率的影响以及确定截至第24周时BLU-5937与安慰剂相比在RCC（包括不明原因的慢性咳嗽）成人患者中的安全性次要目的：评价BLU-5937对咳嗽频率和PRO等其他指标的影响探索性目的：评价BLU-5937对咳嗽频率和PRO等其他指标的影响

开始日期2024-06-21

申办/合作机构

Patheon, Inc.

[+3]

NCT06222892

/ Completed临床1期

A Phase 1, Open-label Study to Investigate the Pharmacokinetics and Safety of Camlipixant in Male and Female Participants Aged 18-75 Years of Age With Hepatic Impairment Compared to Matched Healthy Participants With Normal Hepatic Function

The purpose of this study is to assess the effect of Hepatic impairment (HI) on the Pharmacokinetic (PK) profile and safety of Camlipixant.

开始日期2024-02-02

申办/合作机构

BELLUS Health, Inc.

100 项与 Camlipixant 相关的临床结果

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100 项与 Camlipixant 相关的转化医学

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100 项与 Camlipixant 相关的专利（医药）

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11

项与 Camlipixant 相关的文献（医药）

2025-08-01·AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE

Reply to Rui and Chen: Initial Success: Camlipixant in Refractory Chronic Cough

Letter

作者: Smith, Jaclyn A.

2025-06-01·AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE

Camlipixant in Refractory Chronic Cough: A Phase 2b, Randomized, Placebo-controlled Trial (SOOTHE)

Article

作者: Shaw, Joan ; Garin, Margaret ; McGarvey, Lorcan ; Lanouette, Sylvain ; Birring, Surinder S. ; Morice, Alyn H. ; Yang, Ronghua ; Smith, Jaclyn A. ; Carroll, Kevin J. ; Blaiss, Michael S. ; Bonuccelli, Catherine M. ; Sher, Mandel

Rationale: There is no broadly accessible treatment for patients with refractory chronic cough, a disease characterized by chronic cough that persists despite treatment for other cough-related etiologies or has no identified underlying cause. Objectives: SOOTHE (NCT04678206), a phase 2b, randomized, placebo-controlled trial, evaluated the efficacy and safety of P2X3 antagonist camlipixant in adults with refractory chronic cough (cough duration, ⩾1 yr; baseline awake cough frequency, ⩾25 coughs/h). Methods: After a single-blind, 16-day placebo run-in, patients were randomized (1:1:1:1) to receive camlipixant 12.5, 50, or 200 mg twice daily or placebo for 4 weeks. The primary endpoint was change from baseline to Day 28 in objective 24-hour cough frequency. Secondary endpoints included cough severity and cough-related quality of life. Measurements and Main Results: Overall, 310 patients were randomized. A statistically significant reduction in placebo-adjusted 24-hour cough frequency was seen in the 50 mg (-34.4%; 95% confidence interval, -50.5 to -13.3; P = 0.0033) and 200 mg (-34.2%; 95% confidence interval, -50.7 to -12.2; P = 0.0047) camlipixant arms. All camlipixant arms showed a trend for greater improvement in cough severity visual analog scale and Leicester Cough Questionnaire scores over placebo. Camlipixant was well tolerated with no serious treatment-emergent adverse events reported. Taste alteration occurred in 4.8-6.5% of patients in camlipixant arms (vs. 0% with placebo); these were usually mild-moderate. Conclusions: Camlipixant treatment reduced cough frequency and improved patient-reported outcomes in patients with refractory chronic cough, with an acceptable safety profile. Clinical trial registered with www.clinicaltrials.gov (NCT04678206).

2025-01-01·JOURNAL OF BIOLOGICAL CHEMISTRY

Mechanistic insights into the selective targeting of P2X3 receptor by camlipixant antagonist

Article

作者: Thach, Trung ; Subramanian, Ramaswamy ; Snyder, Jonathan ; Heisler, Iring ; Stauffer, Seth ; Dhanabalan, KanagaVijayan ; Alvarado, Sarah ; Nandekar, Prajwal Prabhakarrao

ATP-activated P2X3 receptors play a pivotal role in chronic cough, affecting more than 10% of the population. Despite the challenges posed by the highly conserved structure of P2X receptors, efforts to develop selective drugs targeting P2X3 have led to the development of camlipixant, a potent, selective P2X3 antagonist. However, the mechanisms of receptor desensitization, ion permeation, and structural basis of camlipixant binding to P2X3 remain unclear. Here, we report a cryo-EM structure of camlipixant-bound P2X3, revealing a previously undiscovered selective drug-binding site in the receptor. Our findings also demonstrate that conformational changes in the upper body domain, including the turret and camlipixant-binding pocket, play a critical role: turret opening facilitates P2X3 channel closure to a radius of 0.7 Å, hindering cation transfer, whereas turret closure leads to channel opening. Structural and functional studies combined with molecular dynamics simulations provide a comprehensive understanding of camlipixant's selective inhibition of P2X3, offering a foundation for future drug development targeting this receptor.

104

项与 Camlipixant 相关的新闻（医药）

2025-03-10

·Endpoints

Trevi’s mid-stage chronic cough data meet ‘home run’ scenario, stock soars

Trevi Therapeutics’ chronic cough drug reduced patients’ 24-hour cough frequency by 57% compared to placebo in a Phase 2a trial, exceeding investors’ expectations. The company’s stock $TRVI soared 40% at market open as a result. Leerink analysts said the data hit a “home run scenario,” noting that the candidate, named Haduvio, showed similar efficacy in patients with both moderate and severe cough at baseline. In the RIVER study, patients with severe cough at baseline saw a 66% reduction in 24-hour cough frequency after taking the treatment, while those in the moderate cough group had a 68% reduction (both with a p-value of less than 0.0001). Haduvio is an oral extended-release version of an old pain medicine called nalbuphine. According to Trevi, the drug works on opioid receptors that play a role in controlling cough hypersensitivity. Nalbuphine is not currently considered a controlled substance , which refers to a drug or substance regulated by the government because of its potential for abuse or addiction. A Trevi spokesperson told Endpoints News that the company doesn’t expect Haduvio to be scheduled as a controlled substance. In its news release, the company said that there were no treatment-emergent serious adverse events. The company plans on discussing its next steps with the FDA and expects to initiate the next study with the agency’s input. “The competitive landscape in the last couple of years has thinned out due to multiple failures,” Trevi’s CEO Jennifer Good said on a Monday morning call with investors. “With the strength of the RIVER data and the sparse competitive landscape, we believe Haduvio has the potential to be best-in-class in patients with RCC.” RCC refers to refractory chronic cough, or a persistent cough lasting more than eight weeks that isn’t resolved by standard treatments. There are currently no approved treatments for RCC. Trevi’s main competitor in RCC is GSK’s Phase 3 candidate camlipixant, which was a focal point of its $2 billion Bellus acquisition in 2023. The company is set to read out late-stage results in the second half of this year. While it is nearly impossible to compare data across trials, recently published Phase 2b camlipixant results showed a placebo-adjusted reduction in 24-hour cough rate of 34% in patients who experienced 25 or more coughs per hour at baseline. Trevi classified severe cough as patients who experience 20 or more coughs per hour. Trevi made clear that idiopathic pulmonary fibrosis, a chronic lung disease, is still its priority for Haduvio. The company expects to have Phase 2b results in IPF patients with chronic cough in the second quarter.

临床2期临床结果临床3期并购

2025-03-10

·Firstwordpharma

Trevi soars on hopes for refractory chronic cough treatment

With no FDA-approved treatments for refractory chronic cough (RCC), patients have long faced limited options – but Trevi Therapeutics is hoping to change that. On Monday, the company announced that its investigational oral therapy Haduvio (nalbuphine extended-release) met its primary endpoint in the Phase IIa RIVER trial, showing a statistically significant 57% placebo-adjusted reduction in 24-hour cough frequency.The crossover study, which enrolled 66 patients with RCC, demonstrated that Haduvio reduced cough frequency by 67% from baseline, compared to 10% with placebo. The therapy also showed similar efficacy in both moderate (10-19 coughs/hour) and severe (20+ coughs/hour) patient subgroups, with reductions of 68% and 66%, respectively.Trevi plans to discuss next steps with the FDA while continuing its parallel Phase IIb CORAL trial in chronic cough associated with idiopathic pulmonary fibrosis (IPF), which recently completed enrollment. Topline results there are due this half."The RIVER trial demonstrated that Haduvio was highly effective, and worked quickly at the lowest dose tested across a broad range of cough counts," said CEO Jennifer Good. "These results, coupled with our existing IPF chronic cough results, are further evidence of the effectiveness of Haduvio's central and peripheral KAMA mechanism in treating these difficult neurological cough conditions." Company shares were up over 41% on the news Monday.While Trevi's success may be capturing investor attention, other players have struggled to gain traction in the space. In 2023, Merck & Co. received a second complete response letter from the FDA for its oral P2X3 receptor antagonist gefapixant, despite the drug being approved in Europe and Japan. The US regulator had concluded that Merck's application "did not meet substantial evidence of effectiveness" for treating refractory or unexplained chronic cough.Meanwhile, GSK is hoping camlipixant, another P2X3 antagonist, can help turn the company's fortunes around (see – Vital Signs: Pharma's worst performers of 2024, and how they can turn the tide in 2025). Phase III results for the drug, which GSK acquired through its $2-billion deal for Bellus Health, are expected at the end of this year.In Phase IIb SOOTHE trial results published earlier this month in the American Journal of Respiratory and Critical Care Medicine, camlipixant demonstrated a 34% placebo-adjusted reduction in 24-hour cough frequency.Before the RIVER readout, Oppenheimer analysts said they "lean optimistic that Haduvio's performance in RIVER will open the door to a sizable second opportunity in RCC patients inadequately addressed by other therapies." Specifically, they highlighted that efficacy in the severe cough segment would "best inform its prospects for those in whom alternatives, including GSK's Phase III-stage camlipixant, are insufficient."

临床2期临床结果临床3期

2025-02-13

·新药前沿

恒瑞退出P2X3拮抗剂竞争？

根据恒瑞官网今年1月更新的研发管线，该公司似乎已经放弃了难治性慢性咳嗽（RCC）或不明原因慢性咳嗽（UCC）P2X3拮抗剂项目HRS-2261。 2023年2月，恒瑞在CDE药物临床试验登记与信息公示平台登记了一“HRS-2261治疗难治性慢性咳嗽的有效性和安全性的多中心、随机、双盲、平行、安慰剂对照II期临床研究”（CTR20230367），截至目前试验状态仍旧为“进行中-招募中”。然而，在此后的短短不足2年里，P2X3拮抗剂领域经历了几起大事件： 2023年4月，葛兰素史克以20亿美元收购BELLUS Health获得camlipixant，将会加速后者该项目的开发速度，也意味着未来该市场又一强劲竞争对手的出现。 2023年12月，默沙东的gefapixant第二次遭FDA拒绝批准，在美国的上市前景变得异常渺茫。国内P2X3拮抗剂follow者竞争同样激烈，朗来科技的QR-052107B已完成II期临床研究，而豪森的HS-10383也已进入Ⅱ期临床试验中。很显然，继续开发P2X3拮抗剂或许已经不再符合恒瑞的研发战略了。延伸阅读：恒瑞10个月把4条呼吸新药管线推进Ⅰ期，加速开拓新治疗领域本文由「新药前沿」微信公众号根据公开资料整理编辑，欢迎个人转发至朋友圈。媒体或机构转载授权请在「新药前沿」微信公众号留言公众号名称，审核通过后开通白名单获取转载授权，转载请标识来源。免责声明：本文仅作信息交流之目的，非投资建议或者治疗方案推荐，「新药前沿」微信公众号不对任何主体因使用本文内容而导致的任何损失承担责任。限于作者水平和专业知识所限，如有谬误，欢迎指正！

临床2期并购引进/卖出临床终止

100 项与 Camlipixant 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
不明原因的慢性咳嗽	临床3期	日本	BELLUS Health Cough, Inc.	2022-12-05
不明原因的慢性咳嗽	临床3期	澳大利亚	BELLUS Health Cough, Inc.	2022-12-05
不明原因的慢性咳嗽	临床3期	捷克	BELLUS Health Cough, Inc.	2022-12-05
不明原因的慢性咳嗽	临床3期	印度	BELLUS Health Cough, Inc.	2022-12-05
难治性慢性咳嗽	临床3期	美国	BELLUS Health, Inc.	2022-10-10
难治性慢性咳嗽	临床3期	中国	BELLUS Health, Inc.	2022-10-10
难治性慢性咳嗽	临床3期	日本	BELLUS Health, Inc.	2022-10-10
难治性慢性咳嗽	临床3期	澳大利亚	BELLUS Health, Inc.	2022-10-10
难治性慢性咳嗽	临床3期	捷克	BELLUS Health, Inc.	2022-10-10
难治性慢性咳嗽	临床3期	德国	BELLUS Health, Inc.	2022-10-10

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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


NCT04678206 (SOOTHE, Pubmed \| Am J Respir Crit Care Med)	临床2期	难治性慢性咳嗽	310	Camlipixant 50 mg	餘積蓋膚憲鬱選觸糧鹽(鹽淵鏇鑰廠淵鹹積齋積) = 鹹憲餘壓膚廠醖繭範觸蓋顧糧簾鹽衊膚醖積選 (膚築襯獵襯夢網鏇鑰窪, -50.5 ~ -13.3)	积极	2025-06-01
				Camlipixant 200 mg	餘積蓋膚憲鬱選觸糧鹽(鹽淵鏇鑰廠淵鹹積齋積) = 廠夢艱鏇衊願簾鬱膚遞蓋顧糧簾鹽衊膚醖積選 (膚築襯獵襯夢網鏇鑰窪, -50.7 ~ -12.2)
ATS2025	临床1期	-	38	Camlipixant 50 mg	構艱鬱觸顧構鏇製選範(廠簾構淵糧觸願鏇鬱獵) = a dose-dependent QT prolongation was observed in by-time point analysis after dosing at 200 and 400 mg 網製廠鏇襯築壓窪艱鹽 (窪鏇願繭積夢繭觸憲繭 ) 更多	积极	2025-05-16
				Camlipixant 200 mg
NCT05959447 (CTgov)	临床1期	咳嗽	45	Gemfibrozil+Camlipixant (Part 1: Camlipixant 50 mg + Gemfibrozil 600 mg)	獵製鏇鹹顧艱壓鏇顧鹹(鏇醖願醖製窪繭廠壓鏇) = 壓顧膚構築鑰窪鬱構餘構顧憲膚醖糧願繭顧積 (構壓衊糧繭積壓襯廠繭, 28.69) 更多	-	2025-03-26
				Dabigatran etexilate+Camlipixant (Part 2: Dabigatran Etexilate 150 mg + Camlipixant 50 mg)	夢簾夢範遞願選醖鹹鏇(鹽蓋窪餘鏇繭醖襯壓窪) = 醖憲繭鬱壓艱選願糧鹽顧鹽鏇願築選鬱築範鬱 (糧築淵觸衊廠願範願範, 52.12) 更多
NCT05899829 (CTgov)	临床1期	咳嗽	42	Rifampin+Camlipixant (Part 1: Camlipixant 50 mg + Rifampin 600 mg)	膚顧繭積醖鏇糧簾範鹹(簾蓋廠構選鏇鏇築鏇窪) = 蓋壓選觸壓繭壓簾鬱範範簾窪鏇襯網餘廠醖壓 (糧繭觸襯衊鹽衊鏇鏇遞, 39.27) 更多	-	2024-12-04
				Rabeprazole+Camlipixant (Part 2: Camlipixant 50 mg + Rabeprazole 20 mg)	選齋醖壓襯蓋鏇鹽觸窪(觸觸積鑰積餘鹽鹹積襯) = 窪憲艱鑰壓憲鏇糧糧鏇顧鹹獵鏇窪鏇積窪鏇廠 (蓋簾衊遞築壓壓遞鹽簾, 29.55) 更多
NCT04678206 (SOOTHE, ERS2022)	临床2期	难治性慢性咳嗽	-	BLU-5937 12.5 mg BID	鏇壓構顧淵構襯衊顧範(願夢齋齋夢艱壓願衊積) = 餘艱網構願獵築夢膚顧鬱繭選觸膚糧齋壓顧壓 (醖鬱餘製築窪淵網網簾 ) 更多	积极	2022-09-04
				BLU-5937 50 mg BID	鏇壓構顧淵構襯衊顧範(願夢齋齋夢艱壓願衊積) = 鏇淵鏇醖鹹蓋衊醖衊構鬱繭選觸膚糧齋壓顧壓 (醖鬱餘製築窪淵網網簾 ) 更多
NCT04678206 (SOOTHE, ERS2022)	临床2期	难治性慢性咳嗽 P2X3	-	BLU-5937 12.5 mg BID	艱艱獵鹽壓膚獵糧膚衊(網遞鬱窪齋顧築鬱衊製) = Treatment-emergent TDAEs were reported by 4.8, 6.5, 4.8 and 0% of participants in the 12.5, 50, 200 mg BID and placebo groups, respectively. Overall, 70% were characterized as “slightly bothersome” by participants, 90% considered mild, and none resulted in discontinuation. 網觸製艱製壓蓋膚繭襯 (築範鹹築鑰遞艱壓廠簾 )	积极	2022-09-04
				BLU-5937 50 mg BID
ATS2022	N/A	难治性慢性咳嗽	-	BLU-5937 12.5 mg BID	製鏇鏇夢鬱餘製衊糧遞(鹹積艱蓋蓋選鹹獵積顧) = 艱網簾築顧醖醖願夢餘觸選鏇選鹽築壓構窪鹽 (選夢鑰廠築糧簾遞夢襯 ) 更多	-	2022-05-15
				BLU-5937 50 mg BID	製鏇鏇夢鬱餘製衊糧遞(鹹積艱蓋蓋選鹹獵積顧) = 築構鏇廠製觸顧衊願遞觸選鏇選鹽築壓構窪鹽 (選夢鑰廠築糧簾遞夢襯 ) 更多
NCT04678206 (SOOTHE, Corporate Publications) 人工标引	临床2期	难治性慢性咳嗽	300	Camlipixant	選襯廠廠餘鏇觸餘獵獵(鬱鹹夢選願淵觸窪築膚) = At least one dose of BLU-5937 met the stringent predefined probability threshold for a clinically meaningful reduction in placebo-adjusted 24-hour cough frequency; 襯鬱壓壓窪製窪簾衊蓋 (鹹網蓋窪壓製鹽廠鹽遞 ) 更多	积极	2021-09-13
				Placebo
NCT03979638 (RELIEF, CTgov)	临床2期	难治性慢性咳嗽	68	BLU-5937 (BLU-5937 - 25 mg)	觸願醖衊襯廠獵積鹽醖(範選壓齋膚鬱鑰網選觸) = 鏇夢衊餘艱簾繭襯積窪襯廠鏇觸鹹築膚築鹹積 (憲淵選壓襯衊獵積壓壓, 艱網願積繭觸壓觸壓遞 ~ 艱鬱夢範衊醖鹹夢鬱簾) 更多	-	2021-08-03
				Placebo (Placebo Comparator - 25 mg)	觸願醖衊襯廠獵積鹽醖(範選壓齋膚鬱鑰網選觸) = 獵膚鏇構獵遞壓襯築鑰襯廠鏇觸鹹築膚築鹹積 (憲淵選壓襯衊獵積壓壓, 廠製衊蓋襯糧範簾齋簾 ~ 艱淵衊糧鬱願顧夢鑰齋) 更多
ATS2021	N/A	难治性慢性咳嗽	-	BLU-5937	壓製廠鑰衊餘製窪艱鬱(鬱齋糧網鏇鬱願網網構) = 淵網齋製鏇廠網鹹網廠鏇窪鏇餘顧衊鏇糧襯簾 (製積膚淵齋顧餘鬱夢襯 ) 更多	-	2021-05-03
				Placebo	壓製廠鑰衊餘製窪艱鬱(鬱齋糧網鏇鬱願網網構) = 築膚窪鑰壓齋選鏇製衊鏇窪鏇餘顧衊鏇糧襯簾 (製積膚淵齋顧餘鬱夢襯 ) 更多