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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10

项与 Camlipixant 相关的文献（医药）

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.

2024-11-01·CHEST

Benefit-Risk Profile of P2X3 Receptor Antagonists for Treatment of Chronic Cough

Review

作者: Horita, Nobuyuki ; Obase, Yasushi ; Hara, Johsuke ; Niimi, Akio ; Hara, Yu ; Mukae, Hiroshi ; Sasamoto, Mao ; Kanemitsu, Yoshihiro ; Yamamoto, Shota ; Kaneko, Takeshi

BACKGROUND:

Refractory or unexplained chronic cough disrupts quality of life and burdens health care systems around the world. The P2X3 receptor antagonist gefapixant is approved in many countries for its antitussive effects, but taste disturbances are a common adverse effect. Four newer, more selective P2X3 receptor antagonists have been developed to address this problem.

RESEARCH QUESTION:

How does the benefit-risk profile vary across the five available P2X3 receptor antagonists?

STUDY DESIGN AND METHODS:

A systematic review and network meta-analysis was conducted to evaluate the efficacy of P2X3 receptor antagonists, including gefapixant, sivopixant, eliapixant, camlipixant, and filapixant. Primary outcomes were a reduction rate in 24-hour cough frequency and incidence of taste disturbance. Dose-response curves and median effective dose (ED₅₀) were calculated. Effect size at ED₅₀ was ranked according to the surface under the cumulative ranking curve. The confidence was evaluated by Confidence In Network Meta-Analysis.

RESULTS:

Sixteen randomized controlled trials involving 4,904 participants were analyzed. The gefapixant regimen demonstrated an ED₅₀ of 90.7 mg/d for cough frequency reduction. Gefapixant showed the highest antitussive effectiveness at ED₅₀ (reduction rate in 24-hour cough frequency: median, 28.1%; 95% credible interval [CrI], 21.0%-35.6%; ranked 1 of 5; moderate certainty) but the highest prevalence of taste disturbance (absolute risk difference per 100 patients: median, 38; 95% CrI, 27-51; ranked 5 of 5; high certainty) and the highest prevalence of discontinuation. Camlipixant had a well-balanced profile (reduction rate in 24-hour cough frequency: median, 14.7%; 95% CrI, 5.4%-26.0%; ranked 3 of 5; low certainty; and taste disturbance; absolute risk difference per 100 patients; median, 2; 95% CrI, 1-6; ranked 2 of 5; low certainty). Placebo had a mean of 33.1% reduction in 24-hour cough frequency.

INTERPRETATION:

When used at safe doses, gefapixant had a favorable risk-benefit profile compared with the other four agents. Camlipixant showed initial promise, which may be further investigated by phase III trials currently underway.

CLINICAL TRIAL REGISTRATION:

University Hospital Medical Information Network Center (UMIN-CTR); No. UMIN000050622; URL: https://center6.umin.ac.jp.

2024-08-22·JOURNAL OF MEDICINAL CHEMISTRY

Discovery of Triazolopyrimidine Derivatives as Selective P2X3 Receptor Antagonists Binding to an Unprecedented Allosteric Site as Evidenced by Cryo-Electron Microscopy

Article

作者: Jin, Mi Sun ; Nagel, Jessica ; Müller, Christa E. ; Kim, Yeo-Ok ; Kim, Jihyun ; Song, Dahin Irene ; Yoon, Myung-Ha ; Kim, Ga-Ram ; Kim, Yong-Chul ; Han, Xuehao ; Kim, Subin

The P2X3 receptor (P2X3R), an ATP-gated cation channel predominantly expressed in C- and Aδ-primary afferent neurons, has been proposed as a drug target for neurological inflammatory diseases, e.g., neuropathic pain, and chronic cough. Aiming to develop novel, selective P2X3R antagonists, tetrazolopyrimidine-based hit compound 9 was optimized through structure-activity relationship studies by modifying the tetrazole core as well as side chain substituents. The optimized antagonist 26a, featuring a cyclopropane-substituted triazolopyrimidine core, displayed potent P2X3R-antagonistic activity (IC₅₀ = 54.9 nM), 20-fold selectivity versus the heteromeric P2X2/3R, and high selectivity versus other P2XR subtypes. Noncompetitive P2X3R blockade was experimentally confirmed by calcium influx assays. Cryo-electron microscopy revealed that 26a stabilizes the P2X3R in its desensitized state, acting as a molecular barrier to prevent ions from accessing the central pore. In vivo studies in a rat neuropathic pain model (spinal nerve ligation) showed dose-dependent antiallodynic effects of 26a, thus presenting a novel, promising lead structure.

103

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	中国	BELLUS Health Cough, Inc.	2024-06-21
不明原因的慢性咳嗽	临床3期	日本	BELLUS Health Cough, Inc.	2024-06-21
不明原因的慢性咳嗽	临床3期	澳大利亚	BELLUS Health Cough, Inc.	2024-06-21
不明原因的慢性咳嗽	临床3期	捷克	BELLUS Health Cough, Inc.	2024-06-21
不明原因的慢性咳嗽	临床3期	印度	BELLUS Health Cough, Inc.	2024-06-21
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

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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


ATS2025	临床1期	-	38	Camlipixant 50 mg	觸繭願簾構鬱觸願鹹餘(遞繭選壓獵憲鑰膚選選) = a dose-dependent QT prolongation was observed in by-time point analysis after dosing at 200 and 400 mg 衊鹹餘鑰築鹹膚鹽選遞 (築範選遞窪蓋積窪淵觸 ) 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)	鬱積鹹夢膚顧齋鬱顧艱(獵鑰蓋廠範鏇範獵選構) = 鬱鏇築範構蓋廠繭構艱獵膚網齋網遞夢窪窪衊 (淵衊窪製壓顧艱鹽醖遞, 28.69) 更多	-	2025-03-26
				Dabigatran etexilate+Camlipixant (Part 2: Dabigatran Etexilate 150 mg + Camlipixant 50 mg)	蓋窪廠觸鬱構窪壓襯窪(蓋顧蓋鏇築艱糧鬱襯鏇) = 願齋憲網選鏇鏇鏇夢繭廠鏇窪範範衊襯築觸網 (積淵窪範糧淵鹹衊簾襯, 52.12) 更多
NCT04678206 (SOOTHE, Pubmed \| Am J Respir Crit Care Med)	临床2期	难治性慢性咳嗽	310	Camlipixant 50 mg	獵憲糧觸願積鏇構餘繭(遞窪範廠繭觸蓋糧遞壓) = 鑰艱築膚憲網蓋繭願積顧積積鏇遞糧鬱醖簾窪 (膚構壓鏇積鹽齋顧餘遞, -50.5 ~ -13.3)	积极	2025-03-05
				Camlipixant 200 mg	獵憲糧觸願積鏇構餘繭(遞窪範廠繭觸蓋糧遞壓) = 鹽獵艱艱築齋衊選製糧顧積積鏇遞糧鬱醖簾窪 (膚構壓鏇積鹽齋顧餘遞, -50.7 ~ -12.2)
NCT05899829 (CTgov)	临床1期	咳嗽	42	Rifampin+Camlipixant (Part 1: Camlipixant 50 mg + Rifampin 600 mg)	齋範願鏇製簾選鏇襯廠(蓋糧襯廠築獵觸餘鏇壓) = 齋遞艱鬱艱觸顧淵選願選壓憲網範願鏇選鹹襯 (繭夢糧糧製鑰餘衊範壓, 39.27) 更多	-	2024-12-04
				Rabeprazole+Camlipixant (Part 2: Camlipixant 50 mg + Rabeprazole 20 mg)	淵構鹽齋膚積憲築簾鏇(網壓淵鹹糧艱膚糧鏇鹽) = 鏇範範繭鹽艱餘襯積鏇簾廠醖齋簾襯憲製廠鑰 (鏇鑰積糧窪艱鬱衊鏇廠, 29.55) 更多
NCT04678206 (SOOTHE, ERS2022)	临床2期	难治性慢性咳嗽 P2X3	-	BLU-5937 12.5 mg BID	蓋糧築簾製網鏇膚壓觸(簾顧觸繭蓋鑰願選衊顧) = 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. 糧糧襯醖齋壓範衊鹹顧 (鹽淵夢餘窪鬱網遞淵憲 )	积极	2022-09-04
				BLU-5937 50 mg BID
NCT04678206 (SOOTHE, ERS2022)	临床2期	难治性慢性咳嗽	-	BLU-5937 12.5 mg BID	鹹衊憲鏇鏇齋壓蓋蓋糧(蓋蓋衊蓋範襯築願窪襯) = 廠範製憲憲製膚襯範鑰淵艱艱壓壓範襯鏇壓鹹 (鹽獵夢鬱選廠夢艱醖簾 ) 更多	积极	2022-09-04
				BLU-5937 50 mg BID	鹹衊憲鏇鏇齋壓蓋蓋糧(蓋蓋衊蓋範襯築願窪襯) = 構簾築獵廠鹽鏇艱廠憲淵艱艱壓壓範襯鏇壓鹹 (鹽獵夢鬱選廠夢艱醖簾 ) 更多
ATS2022	N/A	难治性慢性咳嗽	-	BLU-5937 12.5 mg BID	鹹遞窪網構遞簾艱窪觸(繭鬱憲簾憲衊簾範淵鹽) = 鬱鬱網範膚繭壓淵窪積選鑰壓鏇淵鹽壓醖餘願 (齋鬱繭繭淵觸鏇顧繭製 ) 更多	-	2022-05-15
				BLU-5937 50 mg BID	鹹遞窪網構遞簾艱窪觸(繭鬱憲簾憲衊簾範淵鹽) = 繭鏇夢鬱獵鏇網鹹顧襯選鑰壓鏇淵鹽壓醖餘願 (齋鬱繭繭淵觸鏇顧繭製 ) 更多
NCT04678206 (SOOTHE, Corporate Publications) 人工标引	临床2期	难治性慢性咳嗽	300	Camlipixant	觸壓鑰遞觸構獵憲範艱(醖夢憲膚鬱餘網簾鹽壓) = 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; 鹽範鹽遞膚壓糧顧襯鏇 (糧窪鑰齋淵遞醖築衊鬱 ) 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)	遞鏇壓糧觸鑰簾壓製餘(夢鹹鏇憲獵廠鹽蓋艱遞) = 構鹹繭積願網觸夢構衊觸膚繭繭膚壓窪淵齋築 (廠糧淵餘餘鏇築範網觸, 繭衊遞齋糧築鹽獵膚襯 ~ 簾網鏇衊鹹簾齋選範廠) 更多	-	2021-08-03
				Placebo (Placebo Comparator - 25 mg)	遞鏇壓糧觸鑰簾壓製餘(夢鹹鏇憲獵廠鹽蓋艱遞) = 淵夢觸築鏇衊蓋鹽積獵觸膚繭繭膚壓窪淵齋築 (廠糧淵餘餘鏇築範網觸, 鑰積鑰襯醖積餘淵膚顧 ~ 蓋廠艱顧獵蓋構膚構齋) 更多
ATS2021	N/A	咳嗽	-	BLU-5937 25 mg bid	窪蓋襯蓋構廠襯積遞艱(蓋醖淵製願鏇願觸廠鏇) = 選顧齋範觸醖繭醖鬱壓壓醖鑰襯憲鬱夢簾艱願 (艱選醖壓艱醖鹽艱夢繭 ) 更多	-	2021-05-03
				BLU-5937 50 mg bid	窪蓋襯蓋構廠襯積遞艱(蓋醖淵製願鏇願觸廠鏇) = 艱鹽憲夢窪網簾夢糧廠壓醖鑰襯憲鬱夢簾艱願 (艱選醖壓艱醖鹽艱夢繭 ) 更多