A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Safety, Efficacy, and Systemic Exposure of a Single Administration of FX301 Via Nerve Block for Management of Post-surgical Pain Following Bunionectomy

This two-part study will be conducted in male and female patients 18 to 65 years of age undergoing bunionectomy.
Part I - three-step, single ascending dose study design in which two drug loads (low drug load of funapide and high drug load of funapide) and two volumes (high volume and low volume) of FX301 will be explored against placebo in four cohorts of 12 patients each (9 active:3 placebo) for the management of post-surgical pain in patients undergoing bunionectomy.
Part II - expansion cohort to further assess safety, tolerability, systemic exposure, and efficacy of a selected drug load/volume of FX301. An additional 36 patients will be randomized in a 1:1 ratio to receive either FX301 or placebo as a single-injection analgesic nerve block adjacent to the sciatic nerve of the popliteal fossa.

开始日期2021-03-15

申办/合作机构

Flexion Therapeutics, Inc.

[+1]

NCT02365636 / Completed临床2期

A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Topically Applied TV-45070 (4% and 8% w/w Ointment) in Patients With Postherpetic Neuralgia.

This is a study to evaluate the safety and efficacy of 4% and 8% w/w TV 45070 ointment compared with placebo ointment applied topically and twice daily to the area of PHN pain for 4 weeks in patients with PHN

开始日期2015-02-26

申办/合作机构

Teva Branded Pharmaceutical Products R&D, Inc.

NCT02215941 / Completed临床1期

A Randomized, Double Blind, Placebo-Controlled, Parallel Group, Dose Escalation Study to Characterize the Pharmacokinetics and Safety of 8% TV-45070 Ointment Following 7.5 Days of Twice Daily Topical Application in Healthy Subjects

The primary objective of this study is to characterize the pharmacokinetics of TV-45070 in plasma following single and multiple-dose topical application of 8% TV-45070 ointment.

开始日期2014-08-01

申办/合作机构

Teva Branded Pharmaceutical Products R&D, Inc.

100 项与 Funapide 相关的临床结果

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100 项与 Funapide 相关的转化医学

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100 项与 Funapide 相关的专利（医药）

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项与 Funapide 相关的文献（医药）

2023-11-01·Pain

Cutaneous nerve fiber and peripheral Nav1.7 assessment in a large cohort of patients with postherpetic neuralgia.

Article

作者: Fetell, Michael ; Li, Thomas ; Houk, George ; Dockum, Marilyn ; Marinelli, Leslie ; Sendel, Manon ; Vollert, Jan ; Albrecht, Phillip J ; Ruggerio, Elizaeth ; Baron, Ralf ; Rice, Frank L

ABSTRACT:

The mechanisms of pain in postherpetic neuralgia (PHN) are still unclear, with some studies showing loss of cutaneous sensory nerve fibers that seemed to correlate with pain level. We report results of skin biopsies and correlations with baseline pain scores, mechanical hyperalgesia, and the Neuropathic Pain Symptom Inventory (NPSI) in 294 patients who participated in a clinical trial of TV-45070, a topical semiselective sodium 1.7 channel (Nav1.7) blocker. Intraepidermal nerve fibers and subepidermal Nav1.7 immunolabeled fibers were quantified in skin punch biopsies from the area of maximal PHN pain, as well as from the contralateral, homologous (mirror image) region. Across the entire study population, a 20% reduction in nerve fibers on the PHN-affected side compared with that in the contralateral side was noted; however, the reduction was much higher in older individuals, approaching 40% in those aged 70 years or older. There was a decrease in contralateral fiber counts as well, also noted in prior biopsy studies, the mechanism of which is not fully clear. Nav1.7-positive immunolabeling was present in approximately one-third of subepidermal nerve fibers and did not differ on the PHN-affected vs contralateral sides. Using cluster analysis, 2 groups could be identified, with the first cluster showing higher baseline pain, higher NPSI scores for squeezing and cold-induced pain, higher nerve fiber density, and higher Nav1.7 expression. While Nav1.7 varies from patient to patient, it does not seem to be a key pathophysiological driver of PHN pain. Individual differences in Nav1.7 expression, however, may determine the intensity and sensory aspects of pain.

2017-04-01·The Clinical journal of pain3区 · 医学

Safety and Efficacy of a Topical Sodium Channel Inhibitor (TV-45070) in Patients With Postherpetic Neuralgia (PHN)

3区 · 医学

Article

作者: Neville, Judith ; Namdari, Rostam ; Pimstone, Simon N. ; Goldberg, Yigal P. ; Proctor, Katie J.W. ; Fetell, Michael ; Price, Nicola ; Sherrington, Robin P. ; Malamut, Richard ; Vest, Jeffery ; Kaber, Samer

Objective::

The objective was to evaluate the safety and efficacy of TV-45070 ointment, as a treatment for postherpetic neuralgia, and to explore the response in patients with the Nav1.7 R1150W gain-of-function polymorphism.

Materials and Methods::

This was a randomized, placebo-controlled, 2-period, 2-treatment crossover trial. Patients with postherpetic neuralgia with moderate or greater pain received TV-45070 and placebo ointments, each applied twice daily for 3 weeks. The primary efficacy measure was the difference in change in mean daily pain score from baseline compared with the last week of placebo and active treatment. Secondary endpoints included responder rate analyses and a further exploratory analysis of response in carriers of the Nav1.7 R1150W polymorphism was conducted.

Results::

Seventy patients were enrolled and 54 completed the study. TV-45070 was safe and well tolerated. No statistical difference was observed between treatments for the primary endpoint. However, the proportion of patients with ≥50% reduction in mean pain scores at week 3 was greater on TV-45070 than on placebo (26.8% vs. 10.7%, P=0.0039). Similarly, a greater proportion of patients on TV-45070 had a ≥30% reduction in mean pain scores at week 3 (39.3% on TV-45070 vs. 23.2% on placebo, P=0.0784). Of note, 63% of patients with the R1150W polymorphism versus 35% of wild-type carriers had a ≥30% reduction in mean pain score on TV-45070 at week 3 (no inferential analysis performed).

Conclusions::

The 50% responder analysis suggests a subpopulation may exist with a more marked analgesic response to TV-45070.The trend toward a larger proportion of responders within Nav1.7 R1150W carriers warrants further investigation.

2016-07-04·Chemistry (Weinheim an der Bergstrasse, Germany)2区 · 化学

Iron(III)‐Catalyzed Arylation of Spiro‐Epoxyoxindoles with Phenols/Naphthols towards the Synthesis of Spirocyclic Oxindoles

2区 · 化学

Article

作者: Yuan, Rongju ; Luo, Mupeng ; Yu, Linqian ; Liu, Xuesong ; Wei, Wanguo

Abstract:

An efficient and highly regioselective iron(III)‐catalyzed Friedel–Crafts‐type arylation of spiro‐epoxyoxindoles with phenols was developed for rapid access to 3‐(3‐indolyl)‐oxindole‐3‐methanols, which could be further elaborated into benzofuranyl‐spirooxindoles under Mitsunobu conditions. When spiro‐epoxyoxindoles were reacted with naphthols in the presence of a catalytic amount of FeCl3⋅6 H2O in dichloromethane, they underwent a tandem Friedel–Crafts‐type arylation and O‐cyclization to yield novel naphthofuranyl‐spirooxindoles in excellent yields. This method is applied to enable the efficient and highly regioselective synthesis of a small‐molecule inhibitor of the sodium channel Nav1.7 (±)‐XEN402, which is currently in a phase IIb clinical trial for the treatment of pain.

项与 Funapide 相关的新闻（医药）

2024-04-07

·药渡

科瑞斯生物——三大技术平台助力药企进军千亿级别离子通道药物市场

来源：药渡撰文：四月的雨编辑：哦呼离子通道在人体内具有重要作为，作为细胞膜上的“门户”，离子通道控制着离子们的进进出出。而离子通道药物则可以影响这些离子通道，从而调节细胞内外的离子流动，进而改变细胞的功能。例如此类药物可以调节心脏细胞上的钠离子通道，从而调整心脏的节律。离子通道药物由于具有广阔的适应症，如心血管疾病、疼痛以及肿瘤等，因此具有广泛的应用前景。最为重要的是，离子通道药物潜力巨大。离子通道被认为是继GPCR之后第二大类药物靶点，但目前400多个编码离子通道的基因仅仅几十个得到初步的研究。销售额方面，离子通道药物全球销售额大约200亿美元，超千亿人民币，未来还有较大上升空间。离子通道药物虽然潜力巨大，研发壁垒也是较高，纵观研发史，多家巨头药企折戟在此。离子通道药物研发的成与败在众多的在研离子通道药物中，一些药物由于选择性差、毒性大或疗效不佳等原因而导致了最终的失败。在过去的几年，小分子离子通道药物尤其是Nav1.7/Nav1.8抑制剂的遭遇最为悲惨。2018年10月，Biogen宣布其在研Nav1.7抑制剂Vixotrigine临床2期试验失败，临床试验结果表明Vixotrigine未能达到减少患者平均每日疼痛的预期目标。几乎同时，罗氏也宣布终止了从Xenon收购的同类药物RG6029，另一个卖到梯瓦的Xenon同类药物TV-45070遭相似命运。作为VX-548的“兄弟”，VX-150却也难逃失败的命运。VX-150由于药代动力学性质差、临床剂量过大、存在安全性隐患等原因终止了其临床二期。明雨过后见彩虹，离子通道药物终于传来大捷喜讯。2024年1月30日，Vertex公布Nav1.8抑制剂VX-548治疗中至重度急性疼痛的临床3期数据，数据显示，与安慰剂相比,使用VX-548治疗的受试者疼痛有统计学意义上的显著改善,并且在腹部成形术和子宫切除术的随机对照试验中,疼痛在临床意义的减轻。VX-548的单臂研究显示,在长达14天的大范围手术和非手术性疼痛情况下,使用VX-548进行治疗是有效的。在所有三项研究中,VX-548都是安全的。Vertex计划在2024年中期向FDA提交新药申请。作为近年来首款非阿片类急性疼痛药物，VX-548的获批具有里程碑意义。电压门控一直为离子通道药物研发热点，下表1为以Nav1.8靶点为代表的部分在研药物，除VX-548取得临床3期试验成功外，当前还有多款处于临床2期阶段，除此以外还有多款药物处于临床1期阶段，这里就不再一一列举。全球Nav1.8抑制剂研发管线数量并不多，其中还有相当一部分因各种原因被终止临床，目前全球对于离子通道药物的研发仍有巨大的进步空间。表1.在研离子通道药物（部分）除电压门控以外，配体门控、TRP通道等也是当今研发主流靶点，适应症涉及疼痛、咳嗽、癫痫、脑卒中以及退行性疾病、抑郁症以及癫痫等多项适应症。涉及靶点包括嘌呤受体（P2X2, P2X3, P2X2/3, P2X4, P2X7等）、GABA受体（α1β3γ2, α2β2γ2, α5β2γ2, α6β2γ2等）以及NMDA受体（NR1/2A, NR1/2B；NR1/2C, NR1/2D等）等多种，下表2为部分在研药物。表2.在研药物（部分）作为配体门控受体，P2X3以及GABA受体与多种疾病直接相关，并且逐渐成为“优质”靶点。以GABA受体为例，目前该靶点在研药物适应症主要包括抑郁症、癫痫以及麻醉等多种，皆为中枢神经领域的适应症，这也是当今离子通道药物研发的重要方向。进度方面，由奥鸿医药/华西医院所研发的麻醉药物ET-26以处于临床3期阶段，除此以外，还有多款药物处于临床2期阶段。离子通道靶点——高壁垒下蕴含巨大潜力与机遇众多药企在离子通道药物新药研发上折戟沉沙可以看出离子通道药物研发难度之高，究其根本原因则是离子通道药物特异性差、成药性差、研发过程复杂并且副作用难以控制，最后导致了研发成本的升高。对于离子通道药物的研发，其中涉及了药物化学、生物学、药理学等多个领域的知识和技术。高壁垒下蕴藏大机遇，目前离子通道靶向药物的全球销售大约在200亿美元左右。适应症方面，离子通道药物适用于心律失常、疼痛、癫痫、抑郁、慢性阻塞性肺病、自身免疫性疾病以及糖尿病等多个领域，由于适应症范围广阔，未来离子通道药物市场将进一步提高。对于离子通道药物，人体内参与编码离子通道的基因多达400多个，但目前仅有60余个得到初步研究，仍有大量离子通道的功能及与疾病的关系有待阐明，当某一基因或某几个基因的研究获得突破时，或许离子通道药物的研发将更上一层楼，所以未来离子通道药物潜力巨大。当某款离子通道药物取得突破时，迎接它的便是巨大的机遇，VX-548便是如此。VX-548临床3期试验的成功意义重大，意味着患者不再局限于阿片类药物的选择。三期临床成功，对于全球第一大药物市场的美国来说意义重大。依据CDC数据，阿片类药物过量致死率正加速升高，截至2021年，死于药物过量的人数是1999年的六倍多，从2020年到2021年，药物过量死亡人数增加了16%以上，在2021年近10.7万例药物过量死亡中，涉及阿片类药物超75%。由此可见，VX-548获批后必然会成为众多患者的新选择，市场销售额有望款速扩增。图1.美国阿片过量致死率（图片来源：参考文献2）全球多家药企一直在致力于探索新型的镇痛药物，不仅能媲美阿片类药物的镇痛效果，还可以提高安全性并且避免成瘾，如今VX-548应运而生，必然会为Vertex带来巨大的收益。Vertex在VX-150上面折戟沉沙，但是VX-548的成功让其一扫阴霾，或许这就是离子通道药物高壁垒下蕴含巨大潜力与机遇的奇妙之处。科瑞斯生物——三大技术平台助力药企进军千亿级别离子通道药物市场药物研发当然要紧跟相关的指导原则与法规。2019年，FDA颁布了新的离子通道临床前心脏风险评估指导原则，这意味着对于离子通道药物的。临床前对药物心脏安评的结果，将直接关乎到项目的成败。而科瑞斯生物拥有全球顶级的离子通道新药研发服务及药物的临床前心脏风险评估平台，可为客户提供优质的服务，确保项目更快、更稳的推进。科瑞斯生物成立于2013年，是国内最早能提供离子通道靶点新药研发及专业化临床前药物心脏安全评估平台的企业。公司拥有多套先进的仪器和设备，能够提供从细胞到整体动物的不同水平的测试平台以及高通量化合物筛选平台。目前科瑞斯生物拥有三大服务平台，将助力您更好的进行离子通道药物研发。国内首家可提供临床前心脏安全评估平台科瑞斯生物临床前心脏安全评估平台涉及的技术主要包括手动膜片钳、细胞内动作电位记录、离体心脏灌流系统以及无创伤遥感系统等。由于离子通道药物临床上经常发生由于心电图QT延长而导致的室性扭转性心律失常(TdP)，这将导致药物的研发失败或药物退市。并且由于室性扭转性心律失常的产生几率非常低且在大多数临床实验中是检测不到的，所以药物前临床研发中进行心脏安评是非常有必要的。检测项目主要包括观察药物对hERG离子通道，心电图QTc及心脏上其他主要离子通道包括钠、钙、钾通道等8-10种离子通道的作用、药物对心肌细胞动作电位、离体心脏QTc的影响等，其中hERG及体外QTc是目前新药临床申请所必须提供的数据之一。而科瑞斯生物曾参与FDA及相关机构的CiPA 的工作，在心脏安评方面具有丰富的经验以及过硬的平台技术。图2.科瑞斯生物临床前心脏安全评估平台以离子通道为靶点的新药研发平台离子通道是细胞膜或细胞器膜表面的可以形成离子通透性通道的蛋白质，广泛参与机体细胞的众多生理过程，譬如：神经传导，肌肉收缩，感觉的形成，细胞的分泌，细胞增生和分化，学习与记忆，免疫反应等。离子通道的功能异常会导致诸多疾病，因此离子通道是非常具有吸引力的药物靶点，在新药研究中有着重要作用。科瑞斯生物离子通道为靶点的新药研发平台主要包括四大板块，分别为镇痛、房颤、离体心脏缺血模型以及脑片长时程增强记录。图3.科瑞斯生物离子通道新药研发平台临床前药物研发服务平台科瑞斯生物临床前药物研发服务平台业务包括靶点验证、活性化合物发现、活性化合物到先导化合物的筛选以及先导化合物的优化。目前科瑞斯生物已经开发出近100种离子通道相关的研发及化合物筛选平台，适应症方面则包括镇痛、癫痫、抑郁症、中风、慢性咳嗽以及心衰等多种。图4.科瑞斯生物临床前药物研发服务平台除此以外，科瑞斯生物与Reaction Biology Corporation (RBC)达成战略伙伴关系，RBC药物研发服务平台可提供细胞试验服务、生化试验服务、生物物理测定服务、重组蛋白以及动物实验等多项服务。科瑞斯生物建立的药物心脏安评平台及新药研发平台，是中国国内首个专业化的药物心脏风险评估公司，其技术在国内处于先进地位，并且与国际保持同步。小结离子通道药物有望为许多疾病的治疗带来新的可能性，但在开发和应用过程中，仍需深入的研究以确保药物安全有效的用于临床。关于科瑞斯科瑞斯·总部电话：0513-68015200邮箱：infor@pharmacorelab.com地址：江苏省海门市临江新区海门生物医药科技创业园科瑞斯·分公司地址：中国(上海)自由贸易试验区蔡伦路780号6D座参考文献[1]https://news.vrtx.com/news-releases/news-release-details/vertex-announces-positive-results-vx-548-phase-3-program[2]https://www.hanghangcha.com/pdf.html[3]科瑞斯生物官网及宣传手册本土Biotech与MNC合作进入2.0时代：汇总分析３起医药并购案例【药企裁员风波不断】三月汇总FDA九个月内批准的三种DMD治疗方法点击蓝字 | 关注我们

临床2期并购临床3期临床失败临床成功

2024-03-25

·药融圈

下个潜在收购标的：加拿大最具潜力biotech，Xenon主攻癫痫、抑郁

▲5月30-31日第八届广州生物医药创新者峰会扫码立即报名注：本文不构成任何投资意见和建议，以官方/公司公告为准；本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及），不代表平台立场。任何文章转载需得到授权。2023年12月，艾伯维宣布以87亿美元收购神经科学领域的生物技术公司Cerevel Therapeutics，囊获多款治疗精神神经类疾病的候选产品组合；紧接着，百时美施贵宝宣布以140亿美元现金收购Karuna Therapeutics，拓展了在神经科学疾病领域的布局。（关联阅读：140亿美金的小分子！Karuna制药背后有何来头？）随着近段时间神经科学领域交易频现，多家跨国药企大举并购入局，曾被称为新药研发“黑洞”的CNS领域似乎又重新激起了行业内的热情。一些拥有后期资产的神经科学公司或有可能成为大型制药公司潜在的并购标的。专注于CNS的加拿大制药公司药融云数据www.pharnexcloud.com显示，Xenon Pharmaceuticals是加拿大一家专注于神经科学疾病领域的生物制药公司，主要以小分子、离子通道药物开发为专长，致力于提供创新疗法，以改善神经系统疾病患者的生活。目前该公司正在推进以神经病学为重点的新型产品管线，以解决高度未满足的医疗需求，重点是癫痫，并与学术和行业合作者开展新药研发项目，专注于神经系统药物开发30年的Neurocrine Biosciences是该公司的合作伙伴。截图自药融云数据库Xenon创立于1996年，2014年登陆纳斯达克（NASDAQ:XENE），截至2024年3月22日，该公司市值超过33.19亿美元，是加拿大少有的市值较高的创新药企。Xenon的过去：“世界首个”基因疗法与疼痛研究Xenon创立之时正值基因组技术取得长足发展的时期，最初公司名为Xenon Bioresearch，2004年更名为Xenon Pharmaceuticals。Xenon当时的定位是一家以临床遗传学为基础的生物制药公司，依托其Extreme Genetics发现平台，研究具有极端特征的罕见人类疾病（包括由离子通道突变引起的疾病），通过识别和表征导致这些特征的单基因缺陷，深入了解人类疾病生物学，以更好地选择治疗靶点。（from families to genes, from genes to drugs.）荷兰生物技术公司uniQure的Glybera（alipogene tiparvovec）被认为是“西方世界首个基因治疗药物”，2012年获欧盟批准治疗脂蛋白脂肪酶缺乏症（LPLD），后因价格原因撤市。Glybera最初的活性成分来自于Xenon的平台。Xenon曾与不列颠哥伦比亚大学（UBC）的合作者一起证明了，人类脂蛋白脂肪酶（LPL）的单基因突变，称为LPLS447X突变，可引起LPL酶活性增加，从而降低甘油三酯水平。2000年8月，Xenon与UBC签订了一项许可协议，根据该协议，Xenon获得了根据UBC控制的若干知识产权利益的全球独家许可，以开发和商业化基因治疗技术和化合物，包括与LPL突变有关的产品，即LPLS447X。几乎同一时间，Xenon与荷兰AMT公司（Amsterdam Molecular Therapeutics，成立于1998年）签订了分许可和研究协议，将根据Xenon控制的若干知识产权授予AMT全球独家分许可，以开发和商业化与LPL突变相关的技术和化合物，即LPLS447X。随后Xenon与UBC和AMT合作开展临床前研究，此后AMT便开发了携带LPLS447X基因的LPL基因治疗产品Glybera。不过该药的上市申请曾因受试者只有27例，以及疗效持续性等质疑三次被拒绝。最终AMT面临资金严重短缺的问题，经营困难，在2012年4月被刚成立的uniQure公司收购。同一年，Glybera终获欧盟批准，uniQure在次年与意大利凯西制药（Chiesi）建立合作，共同将Glybera商业化。不过该药定价高达100万美元，成为当时全球最昂贵药物，获批之后仅卖出一剂，而且是在该患者的主治医生想尽办法为其争取到了医疗保险，才得以支付。如此天价让Glybera再也没有被卖出，直到2017年uniQure与凯西制药宣布放弃Glybera，库存中余下的3份分别以1欧元“卖”给了三名欧洲患者。疼痛研究曾是Xenon的另一个重点。2001年，Xenon得知加拿大纽芬兰的一个家庭有四个成员对疼痛无感，其中一个孩子甚至被钉子穿过了脚都感觉不到疼痛，该公司认为这与遗传学有关。根据新闻报道和口耳相传，Xenon追踪并研究了来自世界各地12个对疼痛不敏感的家庭，Xenon通过研究这些家族的基因组，借助其Extreme Genetics平台发现了对疼痛不敏感的人群的共同特征：单个基因SCN9A的突变，这一突变会导致钠离子通道Nav1.7的功能丧失，进而使人对疼痛不敏感，也就是先天性无痛症（CIP）。这也提示了Nav1.7可能作为镇痛药物开发的关键靶点。基于此，Xenon开发了Nav1.7的小分子抑制剂，拟用于各种伤害性疼痛和神经性疼痛，如红斑性肢痛症（EM）、带状疱疹后神经痛（PHN）、膝骨关节炎疼痛、牙痛等。在全球疼痛治疗药物市场日渐庞大，阿片类药物带来成瘾性危机的背景下，业界对新型镇痛药物需求迫切，Xenon的研究成功吸引了制药大厂的目光，2011和2012年间，该公司就Nav1.7小分子抑制剂TV-45070（前称XEN402）和GDC-0276（后称RG-7893）、GDC-0310（RG6029）分别与Teva和罗氏旗下基因泰克达成了合作。不过，针对Nav1.7靶点的药物开发十分困难，全球尚未有该靶点药物成功获批。2017年6月，Xenon与Teva宣布TV-45070局部疗法治疗带状疱疹后神经痛（PHN）的2期临床研究既未达到主要终点，也未达到次要终点。2018年3月，两家公司宣布终止TV-45070的开发合作。另根据药融云数据库www.pharnexcloud.com提供信息，Xenon与基因泰克合作的两款Nav1.7抑制剂也已停止开发。截图自药融云数据库此外，Xenon还在2009年与默沙东（通过其瑞士子公司Essex Chemie AG）合作，开发治疗心血管疾病的新型小分子候选药物，该合作已在2012年结束。新药研发九死一生，曾经的轰轰烈烈到最后也可能落得一地鸡毛。研发管线进展经历了管线和战略的逐步调整，Xenon现在的目标是建立一家完全整合且盈利的生物制药公司，通过发现、开发和商业化创新疗法，专注于改善癫痫和其他神经系统疾病患者的健康。其战略关键包括：● 利用自身的发现能力，基于该公司对离子通道疾病遗传学的理解，结合专有的生物学和药物化学资产和专业知识，确定开发新的候选产品、药物靶点和/或现有候选产品的新适应症；● 通过临床开发推进选定的专有候选产品；● 有选择地建立合作关系，使公司潜在地扩展内部能力和/或获得更广泛的商业机会；● 通过适应症扩展、收购或引进外部候选产品，识别进一步扩大产品线的机会；● 选择单独或与其他公司合作将候选产品商业化。Pipeline更新至2023年12月与2014年IPO时相比，现在Xenon的临床管线已是大换血，其领先候选产品XEN1101是一款新型小分子Kv7.2/Kv7.3钾通道开放剂，主要开发适应症是癫痫和抑郁症。药融云数据www.pharnexcloud.com显示，该药原研单位是博士伦公司。2017年4月，Xenon与1st Order Pharmaceuticals签订资产购买协议，获得了XEN1101（前称为1OP2198）相关的所有权利。而在此之前，1st Order从加拿大制药公司Bausch Health Companies的间接子公司Valeant Pharmaceuticals Luxembourg S.a.r.l.以及Valeant Pharmaceuticals Ireland Limited、Bausch Health收购了1OP2198，并承担了某些义务，包括潜在的里程碑和特许权使用费。2018年，Xenon从Bausch Health买断了与XEN1101相关的所有未来应支付给Bausch Health的里程碑付款和特许权使用费。对于癫痫适应症，尽管目前市场上有多种抗癫痫药物（ASM），但由于多达50%的患者难以控制癫痫发作或患有严重的难治性癫痫，因此存在大量未满足医疗需求。局灶性癫痫发作（FOS）占美国癫痫人群中最大的部分，全面性癫痫是第二大常见的癫痫形式，约80%的成年全面性癫痫患者会经历原发性全面强直阵挛癫痫（PGTCS）。XEN1101治疗局灶性癫痫发作（FOS）：Xenon公司正在开展XEN1101治疗局灶性癫痫发作的3期临床研究，其中包括两项相同的3期临床试验，分别是X-TOLE2和X-TOLE3，这些试验是在2b期X-TOLE临床试验之后设计的（X-TOLE试验显示，在难治性FOS群体中，XEN1101对于癫痫发作的减少具有统计学意义）。这两项多中心、随机、双盲、安慰剂对照试验正在评估15 mg或25 mg剂量的XEN1101与食物一起作为辅助治疗的临床疗效、安全性和耐受性，每项研究大约有360名局灶性癫痫发作（FOS）患者。主要疗效终点是XEN1101与安慰剂相比，从基线到双盲期间（DBP）的月度癫痫发作频率的中位百分比变化（MPC）。公司预计X-TOLE2研究的患者入组将于2024年下半年完成。XEN1101治疗原发性全面强直阵挛癫痫（PGTCS）：该公司正在开展一项名为X-ACKT的3期临床试验，以支持XEN1101治疗另一项癫痫适应症，即PGTCS的潜在监管递交。这项多中心、随机、双盲、安慰剂对照研究正在评估25 mg剂量XEN1101作为辅助治疗在大约160名PGTCS患者中的临床疗效、安全性和耐受性。主要疗效终点是XEN1101与安慰剂相比，从基线到双盲期间（DBP）的月度PGTCS发作频率的中位百分比变化（MPC）。XEN1101治疗癫痫的开放标签扩展研究：在X-TOLE2、X-TOLE3或X-ACKT试验中度过双盲期后，符合条件的患者可以进入长达三年的开放标签扩展（OLE）研究。此外，正在进行的X-TOLE第2b期OLE研究将继续为XEN1101提供重要的长期数据。XEN1101治疗重度抑郁症（MDD）：2023年11月27日，Xenon报告了XEN1101在MDD患者中的2期概念验证X-NOVA临床试验的顶线结果。该试验是一项随机、双盲、安慰剂对照的多中心临床研究，评估了在168名中度至重度抑郁症（MDD）患者中使用10mg和20mg剂量XEN1101的临床疗效、安全性和耐受性。该试验的主要终点是给药第6周时根据Montgomery-Åsberg抑郁量表（MADRS）评分变化，将XEN1101与安慰剂进行比较。根据顶线结果，XEN1101 10mg组平均减少数值为15.61，20mg组为16.94，而安慰剂组为13.90，未达到统计学上的差异，但XEN1101 20mg组与安慰剂组之间存在明确的剂量反应和临床意义，并且该研究达到了次要疗效终点。另外XEN1101在安全性方面也非常出色，且结果显示XEN1101与显著的体重增加无关（体重增加是许多抗抑郁药物的常见副作用）。因此，该试验虽未达到主要终点，但Xenon当日股价却上涨了17.8%。次月，Xenon宣布完成了3.45亿美元的大规模公开募股。截图自雪球Xenon正在积极评估各种临床和监管途径，以支持XEN1101治疗MDD的后期临床开发，预计将于2024年启动3期临床研究。Xenon还在评估XEN1101未来开发的其他潜在适应症。此外，Xenon正与美国西奈山伊坎医学院合作，支持一项由研究者发起的2期概念验证、随机、平行、安慰剂对照的多中心研究，该研究涉及XEN1101治疗约60名MDD患者。研究的主要目的是评估XEN1101对大脑奖励回路的影响，通过功能性磁共振成像（fMRI）评估的双侧腹侧纹状体活动的变化来衡量。次要目标是分别使用MADRS和Snaith-Hamilton快感量表（SHAPS）测试XEN1101与安慰剂相比，对抑郁症和快感缺乏临床测量的影响。与Neurocrine合作的NBI-921352：NBI-921352是一种选择性Nav1.6钠离子通道抑制剂，正在由Xenon与Neurocrine Biosciences合作开发治疗癫痫，Neurocrine拥有NBI-921352（前称为XEN901）的独家许可。2023年11月，Neurocrine宣布评估NBI-921352在成年局灶性癫痫发作（FOS）患者中疗效的2期临床试验未能证明癫痫发作频率显着降低，Neurocrine不再计划NBI-921352在FOS患者中的进一步开发。不过根据当时的新闻稿透露，另外一项2期临床试验正在进行中，旨在评估NBI-921352在2至21岁的SCN8A基因突变相关发育性癫痫性脑病（SCN8A-DEE）患者中的疗效；作为双方合作的一部分，Neurocrine还在继续推进临床前双选择性Nav1.2/1.6抑制剂。临床前项目：Xenon继续利用其广泛的离子通道专业知识和药物发现能力来识别经过验证的药物靶点并开发新的候选产品。近期的重点是针对Kv7、Nav1.1和Nav1.7的开发候选药物，Xenon预计多个候选药物将在2024年和2025年进入IND-enabling研究。财务状况Xenon Pharmaceuticals目前主要通过出售权益性证券、从被许可方和合作者处获得资金以及债务融资来为公司运营提供资金。截至2023年9月30日，Xenon累计赤字为6.204亿美元。迄今为止，Xenon的收入主要来自合作和许可协议。以下是2022、2021以及2020年度Xenon公司的收入概况：根据Neurocrine的协作条款，2021年9月，基于NBI-921352在欧洲的临床试验申请的监管批准，Xenon收到了总额为1000万美元的里程碑付款（包括450万美元的现金和550万美元的普通股股权投资）。2022年1月，基于美国FDA批准扩大NBI-921352用于SCN8A-DEE人群的研究，包括2至11岁的受试者，Xenon收到了总额为1500万美元的里程碑付款（包括675万美元的现金和825万美元的普通股股权投资）。2021年，Xenon确认了与非阿片类药物疼痛管理公司Pacira BioSciences之间针对PCRX301的全球开发和商业化权利协议相关的300万美元收入，其中包括FDA批准IND申请的100万美元里程碑付款和1b期临床试验启动的200万美元里程碑付款。此后Xenon未从该合作中获得收入。2022年11月，Pacira BioSciences做出终止PCRX-301临床开发的战略决策。Pacira BioSciences通过在2021年11月收购Flexion Therapeutics，获得PCRX301（前身为FX301）的全球权利，再之前称为XEN402（也称funapide），该药是一种Nav1.7抑制剂，配制为热敏水凝胶缓释制剂。以下为Xenon在2020至2022年的运营开支情况：该公司2022年R&D费用为1.058亿美元，G&A费用为3281万美元，增长主要是因为临床试验的推进以及人员相关成本。2022年度净亏损为1.254亿美元。以下为2023年前三季度收入情况：本年度尚未获得许可和合作相关收入。以下为2023年前三季度运营开支情况：截至2023年9月30日，Xenon公司持有现金和现金等价物及有价证券共6.391亿美元，预计将足够覆盖公司2026年之前的运营支出。此文仅用于向医疗卫生专业人士提供科学信息，不代表平台立场，不作任何用药推荐参考：NMPA/CDE；药融云数据www.pharnexcloud.com；FDA/EMA/PMDA；相关公司公开披露（正文图片均来自企业官方，除非另有说明）；https://www.xenon-pharma.com/；https://newsinteractives.cbc.ca/longform/glybera；https://www.wired.com/2017/04/the-cure-for-pain/；https://investor.xenon-pharma.com/news-releases/news-release-details/xenon-pharmaceuticals-confirms-closing-transaction-teva-and；https://investor.xenon-pharma.com/news-releases/news-release-details/xenon-expands-ion-channel-neurology-pipeline-acquisition-new；https://investor.xenon-pharma.com/news-releases/news-release-details/xenon-pharmaceuticals-provides-update-partnered-program；等等本文仅用于向医疗卫生专业人士提供科学信息，不代表平台立场，不作任何用药推荐活动推荐 8月 • NDC2024生物医药创新博览会关键词：抗体、多肽、核酸、核药，XDC、小分子、注册、临床、CMC（点击下方图片查看详情）▼【关于药融圈】药融圈PRHub旨在帮助生物医药科技型企业进行品牌推广及商务拓展服务，针对客户的真实需求制定系统化解决方案，通过“翻译-降维-场景化”将客户的品牌信息以直白易懂的方式被公众知悉，同时在流量渠道覆盖100万+垂直用户基础上实现合作目的，帮助合作伙伴完成从品牌开始到商务为终的闭环营销服务。我们已经完成了数十场线下1000人规模的生物医药研发类会议，涵盖小分子新药，大分子新药，改良型新药，BD跨境交易等多个领域，服务了百余家上市/独角兽/生物技术/制药企业。

并购基因疗法

2023-07-06

·BioSpace

Movers & Shakers, Jan. 29 | BioSpace

Xalud Therapeutics – Diem Nguyen was named chief executive officer of New York-based Xalud Therapeutics, a company developing a non-viral gene therapy platform to treat pathologic inflammation through immune modulation. Nguyen joins Xalud from PPD, Inc., where she served as executive vice president of Biopharma. Prior to PPD, Nguyen worked at Pfizer, where she was global president, Americas, Pfizer Essential Health and Global Sterile Injectables. Nguyen currently serves on the board of Verrica Pharmaceuticals, Vitara and Children’s Hospital of Philadelphia. Faze Medicines – Philip Vickers was named CEO of Cambridge, Mass.-based Faze Medicines, which recently launched with an $81 million Series A financing round. Vickers previously served as president and CEO of Northern Biologics and has worked in a diverse array of senior leadership roles across biotech and leading pharma companies. Prior to Northern Biologics, Vickers served as global head of research and development at Shire Pharmaceuticals. He held leading roles at multiple global biotech and pharma companies, including Merck, Pfizer, Boehringer Ingelheim and Resolvyx Pharmaceuticals. Vickers currently serves on the board of Revance Therapeutics and AVROBIO. Diversigen, Inc. – Eric Palmer, professor of Medicine, Section of Infectious Diseases and Global Health and director of the Duchossois Family Institute at the University of Chicago, joined the scientific advisory board of Diversigen, Inc., a subsidiary of OraSure Technologies Inc. Palmer joined the University of Chicago from Memorial Sloan Kettering Cancer Center where he served as head of the Division of Subspecialty Medicine from 2011 to 2018 and director of the Center for Microbes, Inflammation and Cancer from 2010 to 2019. Umoja Biopharma – Rob Glassman was appointed to the board of directors of Seattle-based Umoja Biopharma. Glassman has served as a senior investment banker for 17 years at Merrill Lynch and has been a Vice Chairman at Credit Suisse since 2015. He has since returned to OrbiMed Advisors as the only venture partner in public equity, having served as a private equity partner from 2009 to 2010. Cidara Therapeutics – Bonnie Bassler and Carin Canale-Theakston were appointed to the board of directors of Cidara Therapeutics. Bassler is a Howard Hughes Medical Institute Investigator and the chair of the department of molecular biology and the Squibb professor in molecular biology at Princeton University. She currently serves as a board member of Regeneron, Kaleido Biosciences and Royalty Pharma. Bassler previously served as a board member of Sanofi, the American Association for the Advancement of Science, the National Science Foundation and the American Academy of Microbiology, where she also served as the president. Canale-Theakston is the CEO and founder of Canale Communications, a life science communications firm. Canale-Theakston serves as vice chair of the board of directors for Biocom California, and co-chairs both the Biocom Capital Development Committee and the board’s nominating and governance committee. Kaléo – Virginia-based Kaléo announced five new appointments at the C-suite and management levels. Kevin Espinoza has been named chief compliance officer. He joins Kaléo from Boston Scientific, where he served as the senior vice president of corporate compliance and a privacy officer. Allison Bridges has been named vice president and general manager of allergy and pediatrics, responsible for directing channel strategy and execution. She previously served as the vice president of access and trade at Kaléo. Tom Assalley has been named vice president of market access. He previously served as a vice president at Eli Lilly, overseeing the National Accounts business unit. T.J. Childress has been named senior director of access and trade. He previously served as the director of finance at Kaléo. Meera Mehta has been named director of sales training. Mehta previously served as director of sales training at Novartis. Taysha Gene Therapies – Timothy J. Douros was named chief legal officer and Tracy M. Porter was named chief people officer at Dallas-based Taysha. Prior to joining Taysha, Douros served as General Counsel at lubebird bio, Inc. Before that, he was Deputy General Counsel and Chief IP Counsel at Bluebird Bio. Before joining Bluebird, he spent nearly 13 years at Cubist Pharmaceuticals, Inc., holding positions of increasing responsibility. Porter most recently served as Head of Human Resources at Audentes Therapeutics. Prior to joining Audentes, she spent time at Medivation Inc., and Bayer Healthcare LLC. Mainstay Medical Holdings – Ireland-based Mainstay made several key appointments to strengthen its leadership team. Elias Tu was named vice president of U.S. Sales; Derek Matteo was named vice president of Marketing; James Knibbs was appointed vice president of UK, Ireland, and Australia; Boris Deutschmann was named Country Manager for Germany; Chip Moebus was named vice president of Reimbursement and Market Access; Richard Herman was named vice president of Operations; and Celia Reyes was named vice president of Human Resources. IVI – Rick Chapman was named chief scientific officer of the Innovation and Value Initiative (IVI). Chapman, who is currently Director of Health Economics at the Institute for Clinical and Economic Review (ICER), will start March 1. Prior to ICER, Chapman was a vice president of Health Economics and Outcomes Research (HEOR) at Avalere Health. Chapman was also a principal in HEOR and U.S. regional lead for the Retrospective Database Analysis Center of Excellence at IMS Health. Previously, he was at the Center for Risk Analysis at the Harvard School of Public Health. Karuna Therapeutics – Ronald Marcus was named Senior Vice President of Medical for Karuna Therapeutics, Inc. Marcus will provide strategic and operational leadership of Karuna’s clinical stage pipeline of novel neuropsychiatric medicines, including KarXT. Marcus spent 23 years at Bristol-Meyers Squibb in senior clinical leadership roles within their Neuroscience division, including Executive Director, Neuroscience Global Clinical Research. Marcus also oversaw the Neuroscience Protocol Review Committee at BMS for more than 20 years. Exact Therapeutics – Norway’s Exact Therapeutics announced Hilary McElwaine-Johnn was named chief medical officer. McElwaine-Johnn has held a variety of senior medical positions including Vice President, Clinical, PowderMed Ltd, CMO of Vantia Ltd, PsiOxus Therapeutics Ltd and most recently Karus Therapeutics. NeonMind – Rob Tessarolo was named president and CEO of Canada’s NeonMind. Most recently he held the position of president and CEO of Mind Medicine Inc., a psychedelic drug discovery and drug development company. Prior to that, Tessarolo was president and CEO of Cipher Pharmaceuticals Inc., a diversified specialty pharmaceutical company. Talis Biomedical – Melissa L. Gilliam was appointed to the board of directors of Talis Biomedical Corporation. Gilliam is the Ellen H. Block Professor of Health Justice and Vice Provost of the University of Chicago. She is also Professor of Obstetrics and Gynecology and Professor of Pediatrics. Gilliam is the founder and Director of the Center for Interdisciplinary Inquiry and Innovation in Sexual and Reproductive Health. Flexion -- Flexion announced that Adam Muzikant has been promoted to chief business officer. Muzikant was instrumental in the transactions that led to the FX201 and FX301 programs and has been a driving force in the development of the company’s pipeline. Marius Pharmaceuticals -- Himanshu H. Shah and Shalin Shah were appointed co-CEOs. Himanshu H. Shah has advised numerous public and private companies over the past decades to help them unlock substantial shareholder value and execute both innovative and pragmatic business strategies. Shalin Shah will also step into the role of co-CEO from CFO and executive vice president of strategy for Marius. ViaCyte – San Diego-based ViaCyte made multiple appointments. Michael Yang was named president and CEO, Steve White was named CTO and Brittany Bradrick was named chief operating officer. Yang joins ViaCyte from Acadia Pharmaceuticals, where he was CCO. Prior to joining ViaCyte, White was vice president Global R&D at Baxter Healthcare. Bradrick was previously CFO for ViaCyte. GENFIT -- Pascal Caisey, CCO and Philippe Motté, chief Regulatory and Quality Officer, have joined the executive team at GENFIT. Caisey joined GENFIT in September 2019 as executive vice president of Commercial Development. He held roles with GSK, BMS, Pfizer, Schering Plough and most recently Boehringer Ingelheim, where he oversaw, as the European Business Manager. Motté joined GENFIT in June 2020 as Senior Vice President of Global Regulatory Affairs. His previous commercial and regulatory roles include positions with Sanofi, GSK, Roche, Ipsen, and AbbVie. Datacubed – Kirk McPoyle was named CCO of Datacubed. Prior to Datacubed Health, he spent four years at Clinical Ink as CCO and held previous leadership positions at Acurian, IQVIA and TAP Pharmaceuticals. PlateletBio – Spark Therapeutics co-founder Steven M. Altschuler was named chairman of the PlateletBio Board of Directors. Altschuler co-founded Spark Therapeutics, taking it from launch to its $4B acquisition by Roche. He is also Chairman of the Board of AsclepiX Therapeutics. Most Read Today

基因疗法并购

100 项与 Funapide 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11156	Funapide	-	DB11769

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
膝关节炎	临床2期	美国	Teva Pharmaceutical Industries Ltd.	2014-04-14
疱疹后神经痛	临床2期	美国	Xenon Pharmaceuticals, Inc.	2010-08-01
疼痛	临床2期	荷兰	Xenon Pharmaceuticals, Inc.	2010-04-01
红斑性肢痛症	临床2期	荷兰	Xenon Pharmaceuticals, Inc.	2010-04-01
牙痛	临床2期	美国	Xenon Pharmaceuticals, Inc.	2009-09-01
肌肉骨骼疼痛	临床2期	美国	-	-
神经痛	临床2期	-	Xenon Pharmaceuticals, Inc.	-
拇囊炎	临床1期	美国	Flexion Therapeutics, Inc.	2021-03-15
术后疼痛	临床1期	美国	Flexion Therapeutics, Inc.	2021-03-15

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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


NCT02068599 (CTgov)	临床2期	-	389	TV-45070 (TV-45070 4%)	範醖襯醖淵觸鏇夢鹹鑰(夢遞積壓餘憲選餘夢衊) = 艱鹹窪廠齋鏇觸衊網廠製網襯憲憲製鑰鹽窪膚 (鹹鏇顧獵夢糧餘鏇衊製, 繭齋淵窪獵網襯網範淵 ~ 憲糧艱廠構膚繭範襯網) 更多	-	2018-10-23
				TV-45070 (TV-45070 8%)	範醖襯醖淵觸鏇夢鹹鑰(夢遞積壓餘憲選餘夢衊) = 觸願繭鑰範窪襯醖簾選製網襯憲憲製鑰鹽窪膚 (鹹鏇顧獵夢糧餘鏇衊製, 獵艱選獵網淵積選醖憲 ~ 積遞醖窪簾蓋鏇艱壓淵) 更多
NCT02365636 (CTgov)	临床2期	疱疹后神经痛	300	TV-45070 (TV-45070 4%)	艱觸餘顧窪鹽膚膚範蓋(顧築憲獵願醖齋襯鑰蓋) = 網範窪觸範衊鏇簾繭膚選窪繭壓廠簾廠積淵壓 (鏇蓋糧觸製鑰膚艱獵糧, 製鑰壓襯襯襯遞蓋鹹憲 ~ 繭網選觸願顧齋膚積壓) 更多	-	2018-10-23
				TV-45070 (TV-45070 8%)	艱觸餘顧窪鹽膚膚範蓋(顧築憲獵願醖齋襯鑰蓋) = 膚醖淵廠選壓膚憲範膚選窪繭壓廠簾廠積淵壓 (鏇蓋糧觸製鑰膚艱獵糧, 築淵憲鹹築膚範鹽艱顧 ~ 襯齋願壓齋壓簾鑰鏇鬱) 更多
NCT01486446 (CTgov)	临床1/2期	红斑性肢痛症	8	XPF-002 (XPF-002)	遞製範餘衊鏇鏇糧選衊(齋遞膚餘襯鹽餘膚遞鹹) = 糧窪餘鹹鏇遞構顧遞築簾網艱醖憲衊顧網鏇窪 (壓鏇築憲簾範鏇鹽膚衊, 餘簾築窪鹽餘鹹窪願遞 ~ 窪襯窪觸製鬱餘顧艱築) 更多	-	2014-04-14
				Placebo (Placebo)	遞製範餘衊鏇鏇糧選衊(齋遞膚餘襯鹽餘膚遞鹹) = 襯淵鏇醖築構範顧顧齋簾網艱醖憲衊顧網鏇窪 (壓鏇築憲簾範鏇鹽膚衊, 鑰範鹹願艱獵醖築廠鹹 ~ 壓鏇鏇壓窪積構淵廠築) 更多
NCT01195636 (CTgov)	临床2期	疱疹后神经痛	70	XPF-002 (XPF-002)	齋淵築鏇鑰壓鏇網築簾(醖夢襯製範壓窪鏇襯築) = 糧齋醖鹽顧遞蓋築糧顧衊餘願壓窪簾獵艱憲觸 (鬱顧衊廠廠廠範簾艱廠, 網製顧鹽簾齋鏇艱醖製 ~ 齋顧築製憲憲觸齋選鹹) 更多	-	2013-11-25
				placebo (Placebo)	齋淵築鏇鑰壓鏇網築簾(醖夢襯製範壓窪鏇襯築) = 糧鑰顧鏇膚鑰觸顧艱選衊餘願壓窪簾獵艱憲觸 (鬱顧衊廠廠廠範簾艱廠, 淵網繭衊獵糧獵觸廠範 ~ 遞廠窪鹹醖膚積積襯憲) 更多
NCT00954356 (CTgov)	临床2期	牙痛	61	placebo (Placebo)	顧繭築膚鏇餘鏇顧願觸(鏇選糧廠鹹願膚築簾糧) = 廠醖選遞鏇遞餘獵齋鬱網醖鑰淵鑰餘鏇憲選簾 (糧選衊遞膚夢遞膚遞膚, 淵鑰觸積鬱夢窪獵廠鹽 ~ 膚憲壓襯繭壓觸積壓夢) 更多	-	2012-06-29
				XPF-001 (XPF-001)	顧繭築膚鏇餘鏇顧願觸(鏇選糧廠鹹願膚築簾糧) = 蓋鏇網淵齋憲製鬱憲夢網醖鑰淵鑰餘鏇憲選簾 (糧選衊遞膚夢遞膚遞膚, 簾醖餘觸範鹽鏇範鑰艱 ~ 衊製齋觸範糧願製膚淵) 更多