The Real-world Treatment Satisfaction by Gefapixiant in Patients With Refractory Chronic Cough in Terms of Cough Improvement and Taste Disturbance. (The RESTORE Study)

Chronic cough has a high global prevalence and it is refractory to such treatments by approximately 20% of patients. Gafapixant is a P2X3 receptor antagonist that has demonstrated the reduction of cough in patients with refractory chronic cough(RCC). Taste disturbance is the most frequent adverse event by gefapixant (approximately 60-70%). Although gefapixant is well-tolerated even if taste disturbance has occurred, the impact of taste disturbance on cough-specific QoL remains to be unclear. Therefore, the investigator would like to evaluate factors related to treatment satisfaction by gefapixant in RCC patients. the investigator hypothesize that taste disturbance will be associated with the improvement of cough specific QoL and treatment satisfaction in RCC patients.

开始日期2024-09-06

申办/合作机构

Nagoya City University

[+1]

JPRN-jRCT1041230149 / RecruitingN/AIIT

Verification of the effect of gefapixant on the pathogenesis of cough and evaluation of the efficacy and safety of gefapixant in refractory chronic cough

开始日期2024-02-07

申办/合作机构-

NCT05813223 / Recruiting早期临床1期IIT

The Effect of Acute and Prolonged Administration of Gefapixant on Cough-related Brain Activity in Patients With Chronic Cough

Recently, a new drug called Gefapixant passed phase III clinical trials for cough suppression in patients with chronic cough. The goal of this clinical trial is to investigate the effect of acute and prolonged administration of the drug Gefapixant on cough-related brain activity in patients with chronic cough. The main question it aims to answer is: does the mechanism of action of Gefapixant on the brainstem and brain circuits regulating cough differ between acute and prolonged therapy in people with chronic cough?
Participants have their brain activity and their sensitivity to cough-inducing substances measured as well as complete questionnaires about their cough before and while taking daily Gefapixant.

开始日期2024-01-01

申办/合作机构

University of Melbourne

[+2]

100 项与 Gefapixant Citrate 相关的临床结果

登录后查看更多信息

100 项与 Gefapixant Citrate 相关的转化医学

登录后查看更多信息

100 项与 Gefapixant Citrate 相关的专利（医药）

登录后查看更多信息

项与 Gefapixant Citrate 相关的文献（医药）

2024-12-01·EUROPEAN JOURNAL OF PHARMACOLOGY

P2X3 and P2X2/3 receptors inhibition produces a consistent analgesic efficacy: A systematic review and meta-analysis of preclinical studies

Article

作者: Marcos-Frutos, Daniel ; Huerta, Miguel Á. ; Tejada, Miguel Ángel ; García-Ramos, Amador ; Nava, Javier de la ; Roza, Carolina ; Huerta, Miguel Á

BACKGROUND:

P2X3 and P2X2/3 receptors are promising therapeutic targets for pain treatment and selective inhibitors are under evaluation in ongoing clinical trials. Here we aim to consolidate and quantitatively evaluate the preclinical evidence on P2X3 and P2X2/3 receptors inhibitors for pain treatment.

METHODS:

A literature search was conducted in PubMed, Scopus and Web-of-Science on August 5, 2023. Data was extracted and meta-analyzed using a random-effects model to estimate the analgesic efficacy of the intervention; then several subgroup analyses were performed.

RESULTS:

67 articles were included. The intervention induced a consistent pain reduction (66.5 [CI95% = 58.5, 74.5]; p < 0.0001), which was highest for visceral pain (114.3), followed by muscle (79.8) and neuropathic pain (71.1), but lower for cancer (64.1), joint (57.5) and inflammatory pain (49.0). Further analysis showed a greater effect for mechanical hypersensitivity (70.4) compared to heat hypersensitivity (64.5) and pain-related behavior (54.1). Sex (male or female) or interspecies (mice or rats) differences were not appreciated (p > 0.05). The most used molecule was A-317491, but other such as gefapixant or eliapixant were also effective (p < 0.0001 for all). The analgesic effect was higher for systemic or peripheral administration than for intrathecal administration. Conversely, intracerebroventricular administration was not analgesic, but potentiated pain.

CONCLUSION:

P2X3 and P2X2/3 receptor inhibitors showed a good analgesic efficacy in preclinical studies, which was dependent on the pain etiology, pain outcome measured, the drug used and its route of administration. Further research is needed to assess the clinical utility of these preclinical findings.

PROTOCOL REGISTRATION:

PROSPERO ID CRD42023450685.

2024-11-01·BIOMEDICINE & PHARMACOTHERAPY

Pharmacological differences in postoperative cutaneous sensitivity, pain at rest, and movement-induced pain in laparotomized mice

Article

作者: Cobos, Enrique J ; Cobos, Enrique J. ; Tejada, Miguel Á ; Cañizares, Francisco J. ; Ruiz-Cantero, M Carmen ; Fernández-Segura, Eduardo ; Cañizares, Francisco J ; González-Cano, Rafael ; Huerta, Miguel Á ; Hasoun, Makeya A. ; Robles-Funes, María ; Ruiz-Cantero, M. Carmen ; Hasoun, Makeya A ; Huerta, Miguel Á. ; Tejada, Miguel Á. ; Santos-Caballero, Miriam

Postoperative pain management is challenging. We used mice with a transverse laparotomy to study tactile allodynia measured by the von Frey test, pain at rest measured by facial pain expressions detected by an artificial intelligence algorithm, and movement-induced pain measured by reductions in exploratory activity. The standard analgesics morphine and ibuprofen induced distinct patterns of outcome-dependent effects. Whereas morphine was more effective in reversing pain at rest compared to tactile allodynia, it was unable to alter movement-induced pain. Ibuprofen showed comparable effects across the three outcomes. Administered together, the compounds induced synergistic effects in the three aspects of postoperative pain, mirroring the known advantages of multimodal analgesia used in clinical practice. We explored the impact of neuroimmune interactions using a neutrophil depletion strategy. This reversed pain at rest and movement-induced pain, but did not alter cutaneous sensitivity. Non-peptidergic (IB4+) and peptidergic (CGRP+) nociceptors are segregated neuronal populations in the mouse. We tested the effects of gefapixant, an antitussive drug targeting non-peptidergic nociceptors through P2X3 antagonism, and olcegepant, an antimigraine drug acting as a CGRP antagonist. Both compounds reversed tactile allodynia, while only gefapixant reversed pain at rest, and none of them reversed movement-induced pain. In conclusion, tactile allodynia, pain at rest, and movement-induced pain after surgery have different pharmacological profiles, and none of the three aspects of postoperative pain can predict the effects of a given intervention on the other two. Combining these measures provides a more realistic view of postoperative pain and has the potential to benefit analgesic development.

2024-11-01·Lancet Respiratory Medicine

Efficacy and safety of gefapixant in women with chronic cough and cough-induced stress urinary incontinence: a phase 3b, randomised, multicentre, double-blind, placebo-controlled trial

Article

作者: Dmochowski, Roger ; Reyfman, Paul A ; Cardozo, Linda ; Nguyen, Allison Martin ; Afzal, Amna ; La Rosa, Carmen ; Birring, Surinder S ; Yao, Ruji ; Dicpinigaitis, Peter ; Lu, Susan

BACKGROUND:

Approximately two-thirds of women with chronic cough have cough-induced stress urinary incontinence (CSUI). We aimed to evaluate the efficacy and safety of gefapixant in reducing CSUI episodes in women with refractory or unexplained chronic cough.

METHODS:

This phase 3b, double-blind, randomised, placebo-controlled trial done at 90 sites in 12 countries enrolled women aged 18 years or older who had chronic cough for at least 1 year, a diagnosis of refractory or unexplained chronic cough, a cough severity visual analogue scale score of 40 mm or more (100 mm maximum), and CSUI for 3 months or more. Participants were randomised 1:1 to oral gefapixant or placebo for 12 weeks. The primary outcome was percentage change from baseline in daily CSUI episodes (7-day average) at week 12. This study is registered with ClinicalTrials.gov (NCT04193176).

FINDINGS:

From May 10, 2020, to Sept 2, 2022, 375 participants were randomised to and treated with gefapixant 45 mg twice daily (n=185) or placebo (n=190). Mean age was 56·4 years (SD 11·4), with mean chronic cough duration of 5·2 years (SD 6·6) and SUI duration of 4·0 years (SD 5·9). Least-squares mean percentage change from baseline in daily CSUI episodes was -52·8% (95% CI -58·4 to -47·1%) for gefapixant and -41·1% (-46·7 to -35·4%) for placebo (estimated treatment difference: -11·7% [95% CI -19·7 to -3·7]; p=0·004). 129 (70%) of 185 participants who received gefapixant and 71 (37%) of 190 participants who received placebo had at least one adverse event. Safety and tolerability were consistent with previous trials of gefapixant; the most frequent adverse events were taste related.

INTERPRETATION:

Gefapixant 45 mg twice daily is the first treatment to show efficacy versus placebo in reducing CSUI episodes in participants with refractory or unexplained chronic cough.

FUNDING:

Merck Sharp & Dohme, a subsidiary of Merck & Co.

项与 Gefapixant Citrate 相关的新闻（医药）

2024-10-24

·新药前沿

罗氏放弃first-in-class慢性咳嗽新药，P2X3拮抗剂带领更多新靶点来了

罗氏在10月23日更新其第三季度管线的时候，将进入Ⅱ期临床试验的咳嗽候选药物RG6341从其新药管线中移除。 RG6341是瞬时受体电位通道锚蛋白1(TRPA1)拮抗剂，由罗氏旗下的基因泰克公司发现的这款咳嗽候选药物，并于去年将其纳入Ⅱ期临床试验。 TRPA1是一种非选择性钙离子通道，在初级感觉神经元中高度表达，作为外源性和内源性刺激的多模式传感器，与神经性疼痛和呼吸系统疾病有关。因此，TRPA1拮抗剂具有治疗与哮喘、慢性肺阻塞性疾病(COPD)、特发性肺纤维化(IPF)或病毒后咳嗽相关的咳嗽或慢性特发性咳嗽以及敏感患者咳嗽的潜力。基因泰克研究团队在解决了凝血问题后，发现了RG6341，并认为可以成为first-in-class的止咳药。罗氏对RG6341这一希望未能通过临床疗效的关键早期测试。在RG6341的Ⅱ期试验中，慢性咳嗽或患者感知的咳嗽严重程度没有出现有临床意义的改善。尽管耐受性良好，没有安全问题，这表明基因泰克克服了毒性研究中发现的问题，但缺乏疗效却成了RG6341致命一击。罗氏对RG6341的放弃意味着这一first-in-class靶点在咳嗽新药开发前景中更加扑朔迷离。而TRPA1拮抗剂治疗咳嗽新药开发者中，勃林格殷格翰可能是最快的追逐者。其开发的BI 1839100用于治疗特发性肺纤维化咳嗽也于近期进入Ⅰ期临床试验研究中。如今行业对于慢性咳嗽新药开发可能会再次转向P2X3靶点。默沙东的Gefapixant是首个发现对难治性慢性咳嗽（RCC）患者有显著疗效的P2X3拮抗剂新型疗法。尽管该药已日本和欧盟获批准上市，却在美国确连续两次遭到FDA拒绝！延伸阅读：默沙东慢性咳嗽新药gefapixant二次遭FDA拒绝，已无领先优势默沙东的Gefapixant治疗难治性慢性咳嗽疗效在美国遭遇FDA质疑，且难以克服的味觉障碍不良反应高发生率，正在让葛兰素史克看到机会。葛兰素史克在2023年4月以20亿美元收购BELLUS Health获得Camlipixant以赶超默沙东，而且在充分对竞争对手进行分析后对Camlipixant的Ⅲ期临床试验进行精心设计：首先，确保试验中的患者确实患有慢性难治性咳嗽。其次，试验只招募病情最严重的慢性难治性咳嗽患者。第三，Ⅲ期研究设有为期六周的安慰剂清除期，在此期间患者停止使用任何其他咳嗽治疗药物，以获得真正的安慰剂效应。此外，Camlipixant对P2X3靶点的选择性更高，这意味着其不良反应会更少，因此，葛兰素史克可以使用更大剂量。 Gefapixant（45mg）味觉障碍不良反应发生率达到了65%，14%的患者因此提前停药。而Camlipixant显示出较低的味觉障碍发生率，且没有停药。在国内，目前也有多家企业在开发P2X3拮抗剂，如朗来科技的QR-052107B、豪森的HS-10383、恒瑞医药的HRS-2261都已进入到Ⅱ期临床试验，还有多几个争对手处于更早期开发中。此外，也有一些其他新靶点探索在咳嗽领域的应用前景。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期临床3期并购临床结果

2024-10-15

·BioSpace

CuraSen Therapeutics Appoints Kathleen Sereda Glaub Chief Executive Officer

Expands Adrenergic Pipeline to Address Neurogenic Orthostatic Hypotension and Major Depressive Disorder in Older Adults SAN CARLOS, Calif.--(BUSINESS WIRE)--CuraSen Therapeutics, Inc., a clinical-stage biopharmaceutical company developing oral, rapid onset, small molecule drugs to treat psychiatric and neurodegenerative diseases, announced today that it has appointed Kathleen Sereda Glaub, MBA, formerly executive chair, as chief executive officer. Dr. Anthony Ford will move to the role of president and chief scientific officer, and continue to lead research and development. Patrick Enright, managing director of Longitude Capital, will become chair of the board. Along with these executive changes, the company announced clinical program updates for its drug candidates that are each designed to restore adrenergic stimulus that declines with age or disease. CuraSen’s most recent development candidate is CuraAX (CST-3056), an alpha-1A adrenoceptor (α 1A -AR) agonist being developed as a treatment for neurogenic orthostatic hypotension (nOH). The company is planning to submit an investigational new drug (IND) application this quarter. A significant orphan indication affecting approximately 120,000-150,000 patients in the U.S., nOH is a dysfunction in the autonomic nervous system common in Parkinson’s disease (PD) and related diseases that causes sudden drops in blood pressure upon standing. This can lead to debilitating dizziness, weakness, cognitive decline and dangerous falls. CuraAX is a selective, CNS-penetrant, α 1A -AR agonist designed to provide cognitive benefit as well as control harmful blood pressure deviations. CuraCN (formerly known as CST-103/CST-107), a beta2 adrenoceptor (β 2 -AR) agonist combination, is targeted for a Phase 2b study in major depressive disorder in adults 65 and older, many of whom also suffer from cognitive decline. These plans are based on the company’s previous Phase 2 clinical study in patients that revealed compelling evidence of anti-depressant efficacy and improvements in cognition tests. CuraXN (formerly known as CST-2032/CST-107), a second β 2 -AR agonist combination, is in development for Alzheimer’s disease (AD) to address both cognitive symptoms and disease progression. All three drug candidates work by restoring adrenergic function that declines with age and, in particular, is lost early in neurodegenerative diseases such as AD & PD. CuraSen’s development candidates have strong potential to improve cognitive function and mood, in addition to addressing specific aspects of disease pathobiology. “We are thrilled to have Ms. Glaub assume the role of chief executive officer as CuraSen seeks to capitalize on the company’s adrenergic platform and clinical data to develop a broad pipeline of drugs for psychiatric and neurodegenerative diseases. These include opportunities for a significant, fast-to-market, orphan opportunity in neurogenic orthostatic hypotension,” said Mr. Enright, board chair. “CuraSen will benefit from the collective and complementary executive experience of both Ms. Glaub and Dr. Ford, both co-founders of the company.” Ms. Glaub brings more than 30 years of experience in biopharmaceutical corporate development, strategy, financing and company-building. She serves on the board of directors of IO Biotech, and previously served on the boards of Codexis, Aligos Pharmaceuticals and Escient Pharmaceuticals. Ms. Glaub was previously chief executive officer of Afferent Pharmaceuticals, which was acquired by Merck in 2016 for $1.25 billion. Under her leadership, the company advanced gefapixant to Phase 3 readiness for the treatment of chronic cough and raised $80 million in additional private funding for Afferent. Previously, she served as president of Plexxikon, and helped develop two FDA-approved drugs, Zelboraf® for metastatic melanoma and Turalio® for tenosynovial giant cell tumor (TGCT). She led Plexxikon’s business and financing strategy, negotiated multimillion-dollar partnerships, and led the sale of the company to Daiichi Sankyo for nearly $1 billion. She previously held positions as senior vice president and chief financial officer of Cell Genesys, treasurer of Genentech, and various finance and treasury roles with Intel Corporation. Ms. Glaub received her BA from the University of California, Berkeley, and her MBA from Northwestern University. “CuraSen’s expertise in adrenergic pharmacology, chemistry and clinical development has led to the discovery of three promising drug candidates focused on some of the most debilitating and common neurodegenerative and psychiatric diseases affecting patients and their families. Our adrenergic target mechanisms are already validated by approved drugs in a range of indications, and we have confirmed the ability to develop CNS-penetrant compounds with a unique approach to safety,” said Glaub. “Given the strong and rapid-onset efficacy signals pointing to an anti-depressant effect in our past studies and our understanding of adrenergic deficits in older adults, we believe there is a unique opportunity to address depression in these patients with CuraCN. With CuraXN, we hope to deliver a transformational treatment for Alzheimer’s disease with our holistic approach to restoring brain functionality and health. Lastly, with CuraAX, we believe we can offer major advantages over current treatments for nOH, including durability of efficacy and cognitive benefit, dosing convenience and improved safety.” About CuraSen Therapeutics CuraSen is focused on the development of new treatments for psychiatric and neurodegenerative diseases, including neurogenic orthostatic hypotension, major depressive disorder and Alzheimer’s disease. CuraSen’s drugs are small molecule, oral tablets designed to activate certain receptor populations in the brain to compensate for decline of the adrenergic system driven by aging and disease. The company has evaluated two β 2 -AR agonist candidates, CuraCN and CuraXN, in multiple Phase 2 clinical studies for effects on memory, attention, executive function and mood, as well as safety and tolerability. CuraSen is planning to submit an IND application by the end of 2024 for its third drug candidate CuraAX, an α 1A -AR agonist, for the treatment of nOH. For more information, please visit . Contacts Susan Kinkead Kinkead Communications susan@kinkeadcomm.com 415-509-3610

临床2期高管变更并购

2024-06-25

·同写意

“没花冤枉钱”的重磅交易TOP10

同写意20周年大会：中国医药创新未来之路！“意”同创新，穿越周期，赢取未来。7月中旬，苏州金鸡湖畔，让我们与“新药写意人”一起为中国医药创新“同写意”！在过去的几年中，大型制药公司纷纷投入巨资，在ADC、核药和减肥药物等热门领域进行巨额押注。 Fierce Pharma此前已整理罗列了2023年全球金额最大的并购交易TOP 10，近日，Fierce Biotech又一次回顾了近年最吸引眼球的、最明智的交易。顾名思义，该篇汇总从“回报”情况评估这些大额交易——哪些重磅交易钱花的不亏？当然，这里的“回报”，包括陆续发布的临床数据、可能的历史性批准，以及组合疗法的规模化应用等等，并综合考虑了交易方在全球市场的长期布局。 1 BMS 140亿美元收购Karuna 2023年的最后一个月，向来“低调”的CNS领域接连发生了两起重磅交易，其中之一就是BMS斥资140亿美元收购Karuna Therapeutics。 Karuna最终被以每股330美元现金收购，较2023年12月21日收盘时的股价溢价53%。收购总价为140亿美元，或扣除预计获得的现金后的127亿美元。这场交易标志着BMS重返神经精神病学领域。可以看到，BMS对于该交易的热情，在目前的会议巡回之旅中有所表现。今年4月展示数据显示，KarXT在精神分裂症中可以持续改善症状，且患者体重不会增加。 BMS有理由说这是一笔明智的交易——早在2023年1月，业内就预测Karuna是制药公司必收购的股票之一。据悉，交易后公布的监管文件中显示，另一家公司曾在最后一刻对Karuna公司发起竞购，难怪BMS会急于完成这笔交易。 KarXT是今年最受期待的药物之一，分析师估计，它可以在2028年带来28亿美元的销售额。FDA预计将在今年第三季度做出审批决定。值得关注的是，该药物的中国市场权益由再鼎医药持有。虽然BMS趁热打铁是明智之举，但真正值得称赞的是开发KarXT的Karuna团队，目前该药物也正在阿尔茨海默病精神病领域进行测试。 2 罗氏巧妙截胡 31亿美元收购Carmot 诺和诺德和礼来都从各自的GLP-1资产中赚取了数十亿美元，其他大药厂也正跃跃欲试。但罗氏的入局方式比较巧妙，在Carmot准备IPO时，罗氏与Carmot进行了秘密收购谈判。最后，Carmot甚至还没来得及登陆纳斯达克，罗氏就抢先一步，以31亿美元（27亿美元预付款）收购了这家Biotech，获得了其皮下和口服肠促胰岛素的临床产品线，包括目前正在进行临床III期试验的每周一次和每天一次注射用GLP-1/GIP双受体激动剂。临床试验正在如期推进。5月份进行的一项为期24周的Ib期研究显示，每周一次的CT-388试验组，经安慰剂调整后的平均体重减轻了18.8%。对比15mg的替尔泊肽的数据——52周体重较基线时减轻了17.5%，该药物未来数据十分可期。同时，Carmot的CT-388如果与罗氏的抗肌肉生长抑制素抗体联合，31亿美元的高昂交易价格就十分合理了。罗氏正在研究RO7204239增强脊髓性肌肉萎缩症患者肌肉的潜力，他们提前布局了减肥药的下半场——减重不减肌。罗氏似乎非常偏爱这笔交易，希望以此为跳板进一步扩大研发规模。在今年2月份与分析师召开的全年收益电话会议上，罗氏制药首席执行官Teresa Graham暗示，“收购Carmot还将带来更多收益”，并称罗氏将把该笔收购所得资产，视为未来在心脏代谢领域以及其他潜在疾病领域开展业务的支柱。 3 诺和诺德收购Inversago 减肥药后继有人诺和诺德在肥胖症领域一直处于领先地位，但这家公司已经在考虑下一步的战略布局。近几个月来，诺和诺德开展了一系列动作，包括2023年8月的两次连续收购。先是以1500万欧元（约合1600万美元）收购了是总部位于丹麦的Embark Therapeutics，这是诺和诺德的一家长期合作企业。另一项收购的对象是加拿大公司Inversago Pharma，总金额高达10.7亿美元，包括未披露的开发和商业里程碑金额，这一收购获得的主要资产是该公司管线CB1反向激动剂INV-202。如果接下来的试验取得成功，这场豪赌将带来丰厚的回报。 Inversago正在研发阻断大麻素CB1受体的药物（INV-202）——16年前，赛诺菲曾因该领域遭受重创，欧洲监管机构因CB1受体阻断剂减肥药Acomplia存在精神障碍风险，撤销了对该药的批准。 INV-202正在糖尿病肾病患者中进行II期试验。但诺和诺德更关注其在治疗肥胖症上的潜力，据悉，该候选药物在Ib期试验中已证明具有减肥效果。诺和诺德已将这种更名为monlunabant的药物转入肥胖症的II期临床试验。此外，原本Inversago旗下名为INV-347的下一代CB1受体阻断剂，也被推向临床。 4 GSK收购Bellus Health 开战默沙东有时，明智的交易，一个主要作用就是向竞争对手开战，GSK在2023年8月斥资20亿美元收购Bellus Health时就是这么做的。 GSK因此获得了慢性咳嗽药camlipixant，其作用机制与默沙东的gefapixant相同。这两种药物都是P2X3的拮抗剂，P2X3是一种外周神经系统受体，可引发神经元过敏，与咳嗽冲动有关。默沙东的gefapixant在监管方面遇到了麻烦，其首次上市申请于2022年被FDA拒批，但在日本和欧洲却已成功上市。2023年末，FDA第二次拒批这款药物。这使camlipixant迎来绝佳机会。 Bellus已经引起了海外分析师们的关注，他们当时称该公司“凭借更具选择性的产品和差异化的数据集，一举成为P2X3抑制剂领域的佼佼者”。到2023年6月GSK完成收购时，其首席商务官Luke Miels将这次收购描述为，“与GSK在呼吸药物领域的优势高度协同”。此后，GSK一直在推进camlipixanIII期临床试验，预期2026年获得FDA批准，在2031年及以后实现大规模销售。 5 渤健73亿美元收购Reata 孤注一掷 2023年7月，渤健宣布以73亿美元收购Reata Pharmaceuticals引发关注。这家公司过去几年一直在走下坡路，73亿美元对于渤健来说并不是一个小数目，渤健2023全年营收仅98.36亿美元，产品收入仅为72.47亿美元。收购最终以每股172.50美元的价格进行，较交易宣布前一天收盘价高出59%。用近全年产品收入押注罕见病，主要为获得Reata的主要资产Skyclarys——这是第一个批准用于治疗遗传性神经疾病弗里德里克共济失调的药物。该药物于2023年2月获得FDA批准，分析师预测，Skyclarys到2030年的销售额有望达到15亿美元。 Reata首席执行官Warren Huff在一份新闻稿中表示：“凭借对罕见病患者和现有商业基础设施的清晰了解，我们相信Biogen能够把Skyclarys确立为治疗这种毁灭性遗传病的标准疗法。” Skyclarys自带一份“优先审批券“，用于加快FDA对药品申请或销售的审查流程。Reata还拥有其他几种针对神经系统疾病的药物，但都处于早期开发阶段。此前备受争议的是，就在这次收购之前，渤健刚宣布计划在2024年底前裁员1000人，占员工总数的11%。裁员是对公司进行重组的一部分，过去三年来，该公司的收入一直在下降。 6 礼来收购Versanis Bio 减肥药物联用的回击去年7月，礼来以19.2亿美元的价格收购了Versanis Bio。Versanis Bio的管线主要是激活素受体II型拮抗剂bimagrumab。礼来如今已经凭借Zepbound占据了领先地位，19.2亿美元的收购价对其他人来说是一笔巨款，但对礼来来说甚至算不上九牛一毛。该交易带来了一种名为bimagrumab的II期单克隆抗体，目前正在对超重或肥胖的成年人进行单独测试，并与司美格鲁肽进行肥胖症的联合临床测试。换句话说，最终买下Versanis Bio如果不是礼来，那就可能是他的老对手诺和诺德。 bimagrumab曾经是诺华的临床资产，其在开发包涵体肌炎时因临床失败而被迫中止。礼来之所以看中Versanis的产品组合，是因为它能与肠促胰岛素药物结合起来，有望实现减脂不减肌。虽然Zepbound和Wegovy对肥胖或超重人群的减肥效果不错，但这些药物可能会导致肌肉损失。因此，借助Versanis，礼来或许有望稳住其减重产品组合及Zepbound在市场上占据多年的主导地位。 7 诺华收购Chinook 变废为宝去年6月，诺华花费32亿美元买下Chinook，该公司手握曾被艾伯维放弃的管线Atrasentan，交易仅四个月，这项资产就为诺华带来了回报。虽然诺华已经有自己的IgA肾病候选药物iptacopan，目前正在进行III期临床试验，但它跟Atrasentan的机制并不相同。该药物最初由艾伯维开发，2013年，该公司因该药物临床数据低于预期而停止了慢性肾病的III期试验。幸运的是，2023年10月公布的一项为期36周的中期分析显示，在该药物的III期研究中，蛋白尿的改善程度明显高于安慰剂组。受此消息鼓舞，诺华计划于2024年上半年在美国申请加速审批，随后不久将提交iptacopan的IgA肾病适应症审批。同时，诺华还从Chinook获得了另一项IgA肾病资产，名为zigakibart，目前正在进行III期试验。诺华首席执行官Vasant Narasimhan在4月份的财报电话会议上解释：“我们认为，拥有三种IgA肾病药物将使我们在患者、医生、美国供应链各个环节以及全球范围内占据有利地位。” 8 罗氏71亿美元收购Televant 前雇主卖“后悔了” 我们可以通过“前雇主”是否难以释怀来判断这笔交易是否“划算”。Televant的情况确实如此，交易达成的几个月后，其前身公司Roivant首席执行官Matt Gline坦言，他仍然对出售Televant感到“后悔不已”。 2022年12月，Roivant与辉瑞合作，成立了一家专注于炎症和纤维化疾病的新公司即Televant，用于开发TL1A定向抗体RVT-3101。一个月后，公布的IIb期数据显示，RVT-3101使32%的IBD患者得到缓解，而安慰剂组这一比例仅为12%。当时，各大制药公司对抗TL1A的兴趣十分浓厚，默沙东以108亿美元收购了Prometheus，赛诺菲也与Teva就IBD治疗药物TEV-574展开了合作。到2023年10月，罗氏以71亿美元拿下了同样热门的Televant。 Gline在1月份表示，收购完成后，他一直感到遗憾，是因为RVT-3101的“机会实在太大了”。罗氏对新收购感到十分满意，并宣布计划今年将RVT-3101投入III期试验。2月份举行的财报电话会议上，罗氏制药首席执行官Teresa Graham形容，该资产“有机会真正重新设定患有毁灭性疾病患者的护理标准”。 Graham对外宣称：“我们相信TL1A还有很多其他的适应症，我们期待着为其探索更多的试验计划。请继续关注它的发展方向，前景一片光明。” 9 BMS收购RayzeBio 冲进核药赛道 BMS一举以41亿美元收购了RayzeBio，加入了核药赛道竞逐，瞄准α射线同位素。收购交易以每股62.50美元的价格进行，这一价格是RayzeBio几个月前IPO价格的三倍多。 BMS的出价，足以击败另外两家也提出报价的未具名公司。竞争和中标价格，也能表明核药领域有多火爆，并使BMS能够与诺华同台竞争。与诺华获批的核药疗法Lutathera和Pluvicto（使用名为镥的β发射同位素）不同，RayzeBio的研究基于名为锕-225的α发射同位素。 RayzeBio的主要资产是RYZ101，该药物靶向生长抑素受体2（SSTR2），这是一种在胃肠胰神经内分泌肿瘤（GEP-NET）和广泛期小细胞肺癌（ES-SCLC）中过度表达的蛋白质。该药物的3期试验目前正在进行中，试验对象为之前接受过镥-177生长抑素疗法治疗的SSTR阳性GEP-NET患者，预计2025年将公布研究数据。 BMS还获得了RayzeBio位于印第安纳波利斯的“最先进”制造工厂。礼来也于2023年进入了核药领域，以14亿美元收购Point Biopharma Global，后者是一家专注于放射性配体疗法且拥有内部制造能力的生物技术公司。 10 阿斯利康收购Fusion 押注RDC BMS并非唯一一家刚踏入核药领域的大型制药公司。阿斯利康也大手笔投资入局，今年3月以24亿美元（预付20亿美元）将Fusion纳入其资产配置。该交易确保FPI-2265的II期临床试验如期推进，该药物可提供锕-225，其释放的能量比诺华的Pluvicto等β疗法更高。阿斯利康认为，FPI-2265有可能成为首个获批用于治疗镥后转移性去势抵抗性前列腺癌的PSMA靶向放射治疗方法。但这笔交易的意义远不止将FPI-2265送上FDA审批关口。在宣布收购消息的一个月后，第一季度财报电话会议上，阿斯利康肿瘤研发部执行副总裁Susan Galbraith热情洋溢地谈到，将“放射性结合物与我们研发线中的其他疗法相结合的巨大潜力，包括下一代免疫肿瘤双特异性抗体、细胞疗法、T细胞接合剂和我们的DNA损伤反应剂”。交易也带来了制造方面的好处，放射性同位素的半衰期较短，而且全球生产基地相对较少，这使得制药公司很难进入该领域。幸运的是，Fusion已经在自己的工厂生产临床GMP剂量，并与服务商展开了密切合作。 Galbraith解释说，这意味着此次收购将加速阿斯利康实现商业规模核药生产能力的目标，并强调这一目标将在“三年内”完成，同时还能确保锕的供应。参考资料： 1.Top 10 smartest deals in biopharma；Fierce Biotech 近期直播推荐:

并购临床3期抗体药物偶联物IPO申请上市

100 项与 Gefapixant Citrate 相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
D11349 D11693	-	-	DB15097

研发状态

批准上市

10 条最早获批的记录,

后查看更多信息

适应症	国家/地区	公司	日期
不明原因的慢性咳嗽	欧盟	Merck Sharp & Dohme BV	2023-09-15
不明原因的慢性咳嗽	冰岛	Merck Sharp & Dohme BV	2023-09-15
不明原因的慢性咳嗽	列支敦士登	Merck Sharp & Dohme BV	2023-09-15
不明原因的慢性咳嗽	挪威	Merck Sharp & Dohme BV	2023-09-15
难治性慢性咳嗽	日本	MSD KK	2022-01-20

未上市

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
压力性尿失禁	临床3期	美国	Merck Sharp & Dohme Corp.	2020-05-10
压力性尿失禁	临床3期	阿根廷	Merck Sharp & Dohme Corp.	2020-05-10
压力性尿失禁	临床3期	哥伦比亚	Merck Sharp & Dohme Corp.	2020-05-10
压力性尿失禁	临床3期	德国	Merck Sharp & Dohme Corp.	2020-05-10
压力性尿失禁	临床3期	危地马拉	Merck Sharp & Dohme Corp.	2020-05-10
压力性尿失禁	临床3期	以色列	Merck Sharp & Dohme Corp.	2020-05-10
压力性尿失禁	临床3期	秘鲁	Merck Sharp & Dohme Corp.	2020-05-10
压力性尿失禁	临床3期	俄罗斯	Merck Sharp & Dohme Corp.	2020-05-10
压力性尿失禁	临床3期	韩国	Merck Sharp & Dohme Corp.	2020-05-10
压力性尿失禁	临床3期	西班牙	Merck Sharp & Dohme Corp.	2020-05-10

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


COUGH-2 (NEWS) 人工标引	临床3期	慢性咳嗽	-	gefapixant (COUGH-1)	醖製鑰窪製醖衊蓋遞積(蓋觸餘範膚觸憲艱廠鏇) = 憲鹽範構鬱膚鏇簾餘衊鹹醖網醖獵觸齋簾壓夢 (繭鹹鹽築鑰齋網願遞構 ) 更多	不佳	2023-11-20
				gefapixant (COUGH-2)	醖製鑰窪製醖衊蓋遞積(蓋觸餘範膚觸憲艱廠鏇) = 選願範選衊鏇窪觸選窪鹹醖網醖獵觸齋簾壓夢 (繭鹹鹽築鑰齋網願遞構 ) 更多
NCT04525885 (MK-7264-030, CTgov)	临床3期	不明原因的慢性咳嗽 \| 难治性慢性咳嗽	161	Placebo (Placebo)	鹽構鏇夢觸糧鬱築簾觸(鹽簾獵淵齋窪願顧鑰選) = 糧遞襯鏇醖構構鬱膚顧淵衊鬱窪壓顧壓願範齋 (鬱選鹽憲鏇膚衊範醖窪, 顧窪餘構夢膚繭窪願構 ~ 襯淵製觸鏇網積糧艱構) 更多	-	2023-10-02
				Gefapixant 15 mg BID (Gefapixant 15 mg BID)	繭簾遞夢構糧壓鏇糧襯(製觸醖衊範淵醖築鑰餘) = 製製鑰壓鹽積廠廠鹽淵網糧齋齋鏇蓋選選壓齋 (觸夢繭襯衊襯鹹餘簾廠, 壓鑰憲獵鬱築鬱顧簾廠 ~ 壓窪獵壓顧鑰醖淵醖觸) 更多
NCT04193176 (7264-042 \| MK-7264-042, CTgov)	临床3期	压力性尿失禁 \| 不明原因的慢性咳嗽 \| 难治性慢性咳嗽	376	Placebo (Placebo)	範糧憲選選選顧糧餘衊(醖鏇齋襯餘積襯範繭衊) = 膚夢願積築範襯選繭鬱餘襯範積觸衊繭廠構獵 (築壓醖遞鬱廠鏇鹹醖簾, 艱簾遞襯齋鹹鑰憲壓壓 ~ 壓鬱簾淵鏇願選鹽廠顧) 更多	-	2023-09-22
				Gefapixant (Gefapixant)	範糧憲選選選顧糧餘衊(醖鏇齋襯餘積襯範繭衊) = 廠艱繭顧觸夢構壓獵醖餘襯範積觸衊繭廠構獵 (築壓醖遞鬱廠鏇鹹醖簾, 網醖餘網繭製繭膚壓構 ~ 願範醖蓋鹽鬱鏇壓觸餘) 更多
NCT04193202 (7264-043 \| MK-7264-043, Pubmed)	临床3期	慢性咳嗽	415	Gefapixant 45 mg BID	膚築衊蓋繭鑰製餘顧鏇(夢簾淵構廠築蓋鹹構廠) = 32% gefapixant vs. 3% placebo participants 壓壓鏇憲願窪襯淵壓觸 (淵蓋糧遞鬱鹽膚鏇夢獵 ) 更多	积极	2023-03-06
				Placebo
NCT03449147 \| NCT03449134 (COUGH-2, Pubmed \| Ann Allergy Asthma Immunol)	临床3期	慢性咳嗽	2,044	Gefapixant	齋範夢選衊淵簾餘網遞(鑰獵蓋壓齋鬱齋願顧憲) = 鏇淵醖願獵夢選襯蓋艱鏇淵遞齋窪夢憲鏇鹹範 (製憲鹹觸構壓廠構遞鏇 )	-	2023-01-01
NCT04193202 (7264-043 \| MK-7264-043, CTgov)	临床3期	不明原因的慢性咳嗽 \| 难治性慢性咳嗽	419	Gefapixant (Gefapixant)	膚壓醖淵鏇觸糧鑰選糧(醖積網製衊蓋夢廠顧蓋) = 鬱獵繭網簾鏇鑰範願膚壓遞鏇簾願獵遞壓膚製 (顧鹹遞蓋窪簾獵壓艱遞, 鏇獵夢蓋鑰夢繭齋觸窪 ~ 壓鑰構襯觸衊壓壓鬱構) 更多	-	2022-10-14
				Placebo (Placebo)	膚壓醖淵鏇觸糧鑰選糧(醖積網製衊蓋夢廠顧蓋) = 壓範顧淵鬱壓鹹製製餘壓遞鏇簾願獵遞壓膚製 (顧鹹遞蓋窪簾獵壓艱遞, 膚顧網襯網糧製衊窪鹽 ~ 網簾襯鏇製獵鹹簾餘網) 更多
NCT03569033 (7264-013 \| MK-7264-013, Pubmed)	临床2期	普通感冒	46	Gefapixant 45 mg	夢艱範簾鹹獵蓋簾鬱膚(窪餘製鬱鏇範網蓋鹽獵) = 鹽遞積艱鏇蓋窪廠艱廠壓繭鏇窪齋顧鏇鹽醖構 (鹽遞蓋繭顧遞壓壓網鬱, ( ~ 2.3, 1.7))	不佳	2022-08-15
				Placebo	夢艱範簾鹹獵蓋簾鬱膚(窪餘製鬱鏇範網蓋鹽獵) = 網願繭製醖糧觸獵鏇糧壓繭鏇窪齋顧鏇鹽醖構 (鹽遞蓋繭顧遞壓壓網鬱 )
NCT03696108 (Pubmed) 人工标引	临床3期	慢性咳嗽	169	gefapixant (15 mg group)	憲襯憲鏇築淵膚構鑰憲(願觸鹹繭鑰衊鹽觸廠觸) = 簾積願遞鏇製窪積蓋願積窪獵夢膚選淵蓋醖製 (鹽淵襯醖襯廠膚鏇壓構 ) 更多	积极	2022-06-22
				gefapixant (45 mg group)	憲襯憲鏇築淵膚構鑰憲(願觸鹹繭鑰衊鹽觸廠觸) = 範顧鹹憲鹹積積糧憲繭積窪獵夢膚選淵蓋醖製 (鹽淵襯醖襯廠膚鏇壓構 ) 更多
Pubmed 人工标引	临床1期	慢性咳嗽	36	Gefapixant	壓糧網鬱範廠願鑰窪鹹(製窪鬱糧蓋艱鬱選襯糧) = 製範製廠願鏇遞鑰簾憲膚鏇艱鹽網壓膚選襯選 (構範艱鏇構糧遞積鑰蓋 )	积极	2022-06-07
				Placebo	壓糧網鬱範廠願鑰窪鹹(製窪鬱糧蓋艱鬱選襯糧) = 鑰願餘齋夢鹹膚願壓憲膚鏇艱鹽網壓膚選襯選 (構範艱鏇構糧遞積鑰蓋 )
NCT02502097 (Pubmed) 人工标引	临床2期	特发性肺纤维化 \| 持续咳嗽	51	gefapixant	艱糧淵醖遞獵憲窪網憲(淵齋顧積築齋衊觸壓夢) = 網網憲繭糧鬱膚蓋廠壓繭鏇網襯襯獵襯積遞蓋 (構襯膚鹽簾醖鹽廠餘觸, -15.6 ~ 2.4)	不佳	2021-12-01
				Placebo	艱糧淵醖遞獵憲窪網憲(淵齋顧積築齋衊觸壓夢) = 糧觸夢壓鏇憲糧醖繭襯繭鏇網襯襯獵襯積遞蓋 (構襯膚鹽簾醖鹽廠餘觸, -14.6 ~ 3.1)