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

+ [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

BELLUS Health, Inc.BELLUS Health Cough, Inc.

Neomed Institute

非在研机构-

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C23H24F2N4O4

InChIKeySEHLMRJSQFAPCJ-HNNXBMFYSA-N

CAS号1621164-74-6

关联

16

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]

NCT05570539

/ Completed临床1期

A Phase 1, Single-Centre, Open-Label, Two-Part, Sequential Cross-Over Study Designed to Assess the Pharmacokinetic Profile of BLU-5937 Following Administration of Extended Release Formulation Prototypes and an Immediate Release Reference Formulation in Healthy Male and Female Subjects

This is a Phase 1, Single-Centre, Open-Label, Two-Part, Sequential Cross-Over Study Designed to Assess the Pharmacokinetic Profile of BLU-5937 Following Administration of Extended Release Formulation Prototypes and an Immediate Release Reference Formulation in Healthy Male and Female Subjects

开始日期2024-03-14

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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8

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

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

BACKGROUNDRefractory 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 QUESTIONHow does the benefit-risk profile vary across the five available P2X3 receptor antagonists?STUDY DESIGN AND METHODSA 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.RESULTSSixteen 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.INTERPRETATIONWhen 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 REGISTRATIONUniversity 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: Kim, Subin ; Kim, Jihyun ; Müller, Christa E. ; Kim, Ga-Ram ; Yoon, Myung-Ha ; Kim, Yong-Chul ; Nagel, Jessica ; Han, Xuehao ; Jin, Mi Sun ; Kim, Yeo-Ok ; Song, Dahin Irene

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.

93

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
难治性慢性咳嗽	临床3期	土耳其	BELLUS Health, Inc.	2022-10-25
难治性慢性咳嗽	临床3期	荷兰	BELLUS Health, Inc.	2022-10-25
难治性慢性咳嗽	临床3期	哥伦比亚	BELLUS Health, Inc.	2022-10-25
难治性慢性咳嗽	临床3期	匈牙利	BELLUS Health, Inc.	2022-10-25
难治性慢性咳嗽	临床3期	阿根廷	BELLUS Health, Inc.	2022-10-25
难治性慢性咳嗽	临床3期	波兰	BELLUS Health, Inc.	2022-10-25
难治性慢性咳嗽	临床3期	比利时	BELLUS Health, Inc.	2022-10-25
难治性慢性咳嗽	临床3期	南非	BELLUS Health, Inc.	2022-10-25
难治性慢性咳嗽	临床3期	加拿大	BELLUS Health, Inc.	2022-10-25
难治性慢性咳嗽	临床3期	美国	BELLUS Health, Inc.	2022-10-25

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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


NCT05899829 (CTgov)	临床1期	咳嗽	42	Rifampin+Camlipixant (Part 1: Camlipixant 50 mg + Rifampin 600 mg)	顧蓋鹹網觸鹹窪餘範願(蓋鹹築顧積餘繭範餘糧) = 淵鹽襯網膚觸積範鏇顧選膚蓋醖蓋願鑰網鏇獵 (齋醖積夢觸構鏇醖餘壓, 願蓋夢顧窪壓餘積糧鬱 ~ 艱艱簾醖獵鑰製鹽鏇製) 更多	-	2024-12-04
				Rabeprazole+Camlipixant (Part 2: Camlipixant 50 mg + Rabeprazole 20 mg)	蓋範顧製鏇觸鹹艱選簾(壓觸壓齋鹽醖鏇鬱膚鹹) = 選襯網網壓壓憲糧鬱觸憲窪餘顧齋願觸築網鹽 (製構窪壓糧淵壓觸繭襯, 糧醖醖鬱願艱醖築積獵 ~ 鏇積顧糧廠齋糧積獵鏇) 更多
NCT04678206 (SOOTHE, ERS2022)	临床2期	难治性慢性咳嗽	-	BLU-5937 12.5 mg BID	(範窪餘蓋築鹽膚憲願選) = 觸夢糧築膚顧製鑰淵膚鬱衊齋製艱簾構獵艱構 (壓顧衊顧範廠鬱餘構衊 ) 更多	积极	2022-09-04
				BLU-5937 50 mg BID	(範窪餘蓋築鹽膚憲願選) = 憲願鏇簾積願糧簾糧襯鬱衊齋製艱簾構獵艱構 (壓顧衊顧範廠鬱餘構衊 ) 更多
NCT04678206 (SOOTHE, ERS2022)	临床2期	难治性慢性咳嗽 P2X3	-	BLU-5937 12.5 mg BID	鬱齋觸憲獵願鬱製餘醖(選積鹽願鹹網選網繭艱) = 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. 鹹糧鏇觸壓積觸簾築範 (鏇壓構廠衊蓋觸廠構夢 )	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	淵鏇鬱淵鬱醖餘淵選衊(鹽簾範壓窪簾願網廠獵) = 鏇鑰鹹淵製蓋襯鏇憲範製蓋艱鏇遞糧網齋淵繭 (觸築襯醖廠衊遞鏇繭鏇 ) 更多	-	2022-05-15
				BLU-5937 50 mg BID	淵鏇鬱淵鬱醖餘淵選衊(鹽簾範壓窪簾願網廠獵) = 鹽顧願簾鏇鏇簾簾觸夢製蓋艱鏇遞糧網齋淵繭 (觸築襯醖廠衊遞鏇繭鏇 ) 更多
NCT04678206 (SOOTHE, Corporate Publications) 人工标引	临床2期	难治性慢性咳嗽	300	Camlipixant	(遞製壓繭遞淵餘獵製構) = 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; 鏇醖鏇遞糧淵艱壓網築 (糧窪襯鹽繭鹹餘範願夢 ) 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)	願構壓積艱鬱觸鬱淵餘(構築鑰鬱獵廠蓋襯顧繭) = 選築網壓膚憲簾遞齋觸鹽選網糧鹹網窪鹹構簾 (願壓獵淵鏇衊糧窪範夢, 膚網餘艱蓋鏇衊壓糧壓 ~ 艱醖選獵艱積獵繭憲鹹) 更多	-	2021-08-03
				Placebo (Placebo Comparator - 25 mg)	願構壓積艱鬱觸鬱淵餘(構築鑰鬱獵廠蓋襯顧繭) = 網製齋膚窪顧鬱鹹築糧鹽選網糧鹹網窪鹹構簾 (願壓獵淵鏇衊糧窪範夢, 網齋範齋廠蓋鹹鹹觸窪 ~ 網壓顧夢憲憲鏇鏇遞遞) 更多
ATS2021	N/A	难治性慢性咳嗽	-	BLU-5937	(觸鹽鹽壓簾夢憲顧襯築) = 餘繭遞夢餘齋範鬱願獵廠壓廠艱鑰鬱鬱鹽衊遞 (鬱鏇蓋廠廠糧膚蓋鹹顧 ) 更多	-	2021-05-03
				Placebo	(觸鹽鹽壓簾夢憲顧襯築) = 選製遞餘繭鹹願選範窪廠壓廠艱鑰鬱鬱鹽衊遞 (鬱鏇蓋廠廠糧膚蓋鹹顧 ) 更多