To assess the long-term safety and tolerability of XEN496 in pediatric subjects with KCNQ2 developmental and epileptic encephalopathy (KCNQ2-DEE) who had participated in the primary study (XPF-009-301).

开始日期2021-08-17

申办/合作机构

Xenon Pharmaceuticals, Inc.

NCT04639310

/ Terminated临床3期

A Phase 3 Study of Adjunctive XEN496 in Pediatric Subjects With KCNQ2 Developmental and Epileptic Encephalopathy

To investigate the potential antiseizure effects of adjunctive XEN496 (ezogabine) compared with placebo in children with KCNQ2 Developmental and Epileptic Encephalopathy (KCNQ2-DEE).

开始日期2021-03-29

申办/合作机构

Xenon Pharmaceuticals, Inc.

CTR20182420

/ Completed临床1期

瑞替加滨片单次给药在健康受试者体内的药代动力学预试验

主要研究目的：本研究以天津红日药业股份有限公司生产的瑞替加滨片（50mg）为受试制剂，评估其在空腹条件下给药后的药代动力学初步特征。

开始日期2018-12-17

申办/合作机构

天津红日药业股份有限公司

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100 项与瑞替加滨相关的临床结果

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100 项与瑞替加滨相关的转化医学

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100 项与瑞替加滨相关的专利（医药）

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951

项与瑞替加滨相关的文献（医药）

2025-04-01·PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Potassium-sensitive loss of muscle force in the setting of reduced inward rectifier K ⁺ current: Implications for Andersen–Tawil syndrome

Article

作者: Cannon, Stephen C. ; DiFranco, Marino ; Spencer, Melissa J. ; Mokhonova, Ekaterina ; Elia, Nathaniel ; Quiñonez, Marbella ; Wu, Fenfen

Andersen–Tawil syndrome (ATS) is an ion channelopathy with variable penetrance for the triad of periodic paralysis, arrhythmia, and dysmorphia. Dominant-negative mutations of KCNJ2 encoding the Kir2.1 potassium channel subunit are found in 60% of ATS families. As with most channelopathies, episodic attacks in ATS are frequently triggered by environmental stresses: exercise for periodic paralysis or stress with adrenergic stimulation for arrhythmia. Fluctuations in K + , either low or high, are potent triggers for attacks of weakness in other variants of periodic paralysis (hypokalemic periodic paralysis or hyperkalemic periodic paralysis). For ATS, the [K + ] dependence is less clear; with reports describing weakness in high-K + or low-K + . Patient trials with controlled K + challenges are not possible, due to arrhythmias. We have developed two mouse models (genetic and pharmacologic) with reduced Kir currents, to address the question of K + -sensitive loss of force. These animal models and computational simulations both show K + -dependent weakness occurs only when Kir current is <30% of wildtype. As the Kir deficit becomes more severe, the phenotype shifts from high-K + -induced weakness to a combination where either high-K + or low-K + triggers weakness. A K + channel agonist, retigabine, protects muscle from K + -sensitive weakness in our mouse models of the skeletal muscle involvement in ATS.

2025-04-01·JOURNAL OF MEDICAL GENETICS

Genetic features and pharmacological rescue of novel Kv7.2 variants in patients with epilepsy

Article

作者: Zhang, Yi ; Yu, Shihui ; Zhang, Jiahui ; Meng, Yuhuan ; Zhang, Xue ; Mao, Di ; Song, Huilin ; Qiao, Shupei ; Sui, Shengbin ; Cao, Tianhua ; Xia, Yang ; Song, Yue ; Xie, Li ; Meng, Lingdi ; Jia, Ying ; Jing, Wenwen ; Peng, Ziyue

Background:

Increasing evidence indicates a robust correlation between epilepsy and variants of the Kv7.2 (KCNQ2) channel, which is critically involved in directing M-currents and regulating neuronal excitability within the nervous system. With the advancement of next-generation sequencing, the identification ofKCNQ2variants has surged. Nonetheless, their functional impacts are still being determined, introducing uncertainty into the diagnostic process for affected families and potentially hindering their ability to participate in targeted precision medicine trials. This study aims to elucidate the pathogenicity of these novel variants and explore potential therapeutic interventions.

Methods:

Whole-cell patch-clamp recordings, western blotting, and immunofluorescent staining were performed to elucidate the functional consequences of the identified variants. Moreover, coimmunoprecipitation techniques were conducted to explore protein interactions, thus facilitating a deeper understanding of the underlying pathogenetic mechanisms contributing to the disease. Ultimately, the effects of pharmacological interventions were evaluated in vitro using the patch-clamp technique.

Results:

Herein, we identified 12 novelKCNQ2variants, further expanding the mutational spectrum ofKCNQ2. Our investigation revealed that one gain-of-function variant (p.L102V (c.304C>G)) and three loss-of-function variants (p.H328Q (c.984C>G), p.A336V (c.1007C>T) and p.D563Efs*22 (c.1688_1689insACTT)) had different impacts on the binding of calmodulin and phosphati-dylinositol-4,5-bisphosphate, potentially altering their localisation and protein stability. Furthermore, the application of ML213, unlike Retigabine and ICA-069673, led to a significant increase in the current of p.H328Q.

Conclusion:

This study expanded the mutational spectrum ofKCNQ2and analysed the genetic and functional consequences, as well as the pharmacological rescue, of fourde novo KCNQ2variants. These findings offer valuable insights into the precise medicine ofKCNQ2-related epilepsy.

2025-03-01·CNS DRUGS

Targeting Kv7 Potassium Channels for Epilepsy

Review

作者: Taglialatela, Maurizio ; Perucca, Emilio

Voltage-gated Kv7 potassium channels, particularly Kv7.2 and Kv.7.3 channels, play a critical role in modulating susceptibility to seizures, and mutations in genes that encode these channels cause heterogeneous epilepsy phenotypes. On the basis of this evidence, activation of Kv7.2 and Kv.7.3 channels has long been considered an attractive target in the search for novel antiseizure medications. Ezogabine (retigabine), the first Kv7.2/3 activator introduced in 2011 for the treatment of focal seizures, was withdrawn from the market in 2017 due to declining use after discovery of its association with pigmentation changes in the retina, skin, and mucosae. A novel formulation of ezogabine for pediatric use (XEN496) has been recently investigated in children with KCNQ2-related developmental and epileptic encephalopathy, but the trial was terminated prematurely for reasons unrelated to safety. Among novel Kv7.2/3 openers in clinical development, azetukalner has shown dose-dependent efficacy against drug-resistant focal seizures with a good tolerability profile and no evidence of pigmentation-related adverse effects in early clinical studies, and it is now under investigation in phase III trials for the treatment of focal seizures, generalized tonic-clonic seizures, and major depressive disorder. Another Kv7.2/3 activator, BHV-7000, has completed phase I studies in healthy subjects, with excellent tolerability at plasma drug concentrations that exceed the median effective concentrations in a preclinical model of anticonvulsant activity, but no efficacy data in patients with epilepsy are available to date. Among other Kv7.2/3 activators in clinical development as potential antiseizure medications, pynegabine and CB-003 have completed phase I safety and pharmacokinetic studies, but results have not been yet reported. Overall, interest in targeting Kv7 channels for the treatment of epilepsy and for other indications remains strong. Future breakthroughs in this area could come from exploitation of mechanistic differences in the action of Kv7 activators, and from the development of molecules that combine Kv7 activation with other mechanisms of action.

项与瑞替加滨相关的新闻（医药）

2025-03-12

·PRNewswire

QurAlis Announces Topline Data From its Phase 1 Clinical Trial of QRL-101 Evaluating Biomarkers of ALS and Epilepsy in Healthy Volunteers

Results demonstrated statistically significant effects on biomarkers that predict ALS disease progression and severity Evidence of brain penetration, target engagement, and potential anti-seizure effects demonstrated through biomarkers for TMS-EMG and EEG Safety and tolerability profile consistent with previously reported results for QRL-101 QurAlis intends to advance QRL-101 into proof-of-concept studies as a potentially best-in-class treatment for both ALS and epilepsy CAMBRIDGE, Mass., March 12, 2025 /PRNewswire/ -- QurAlis Corporation ("QurAlis"), a clinical-stage biotechnology company driving scientific breakthroughs into powerful precision medicines that have the potential to alter the trajectory of neurodegenerative and neurological diseases, today announced positive topline data from QurAlis' Phase 1 proof-of-mechanism (PoM) clinical trial of QRL-101 in healthy volunteers evaluating biomarkers related to amyotrophic lateral sclerosis (ALS) and epilepsy. Topline results demonstrated a dose-dependent, statistically significant decrease in motor nerve excitability threshold tracking (mNETT) strength-duration time constant (SDTC), the co-primary endpoint of the trial related to ALS. SDTC is a well-established electrophysiological biomarker of peripheral motor excitability related to ALS, where elevation of SDTC has been clinically shown to predict faster disease progression and mortality. The decrease in SDTC observed with QRL-101 in this study was approximately 50% greater than previously reported for the Kv7 potassium channel opener ezogabine in a single-dose study in people with ALS. Additional observations for multiple secondary and exploratory endpoints related to motor nerve excitability were also significantly impacted. The clinical trial demonstrated a statistically significant impact on multiple secondary and exploratory endpoints related to epilepsy. These included transcranial magnetic stimulation electromyography (TMS-EMG) intracortical facilitation which indicates effective inhibition of cortical excitability, as well as significant increases in electroencephalography (EEG) spectral power in beta and gamma spectral bands further demonstrating cortical target engagement and brain penetration. There was minimal to no impact on the slower delta and theta EEG bands, which suggests a low potential for GABA-A receptor activation and sedation. The study did not reach statistical significance on the co-primary endpoint of TMS-EMG motor evoked potential (MEP) amplitude, another measure of corticospinal excitability. Results also demonstrated that the safety and tolerability profile of QRL-101 was consistent with previously reported study results evaluating QRL-101 to date. There were no serious adverse events or discontinuations due to adverse events reported observed in the study. "We are excited by these topline data from our biomarker study in healthy participants which suggest that QRL-101 has the potential to provide a therapeutic effect for both ALS and epilepsy," said Kasper Roet, Ph.D., CEO and co-founder of QurAlis. "Loss of Kv7.2/7.3 function from the mis-splicing of the KCNQ2 gene leading to hyperexcitability-induced neurodegeneration was one of the first genetic breakthroughs from human ALS motor neuron stem cell models made by our founders at Harvard. QurAlis was started to develop a best-in-class Kv7 ion channel opener for the treatment of hyperexcitability-induced disease progression in ALS, which occurs in about half of all people living with ALS. Elevated SDTC has been clinically linked to faster disease progression and mortality, underscoring the need for an effective treatment for this population." Dr. Roet continued, "The decrease in SDTC observed with QRL-101 in this study was approximately 50% greater than previously reported for the Kv7 opener ezogabine in a single-dose study in people with ALS. QRL-101 has the potential to be a promising therapeutic, especially considering the encouraging results from a previous study with ezogabine in ALS patients showing positive effects on both SDTC and the disease progression biomarker compound muscle action potential (CMAP). Further, based on the strong clinical validation of Kv7.2/7.3 ion channel openers in seizure reduction, the TMS-EMG intracortical facilitation together with the EEG data from this study suggest QRL-101 may have the potential to reduce both frequency and severity of seizures in people living with epilepsy without causing sedation. We are encouraged by these results and look forward to advancing the clinical program for QRL-101 in both ALS and epilepsy so that we can fulfill our mission of bringing much-needed precision medicine options to patients." Kv7.2/7.3 is a voltage-gated potassium channel whose role is crucial for the regulation of both neuronal excitability and membrane potential. QRL-101 is a potentially best-in-class selective Kv7.2/7.3 ion channel opener for the treatment of hyperexcitability-induced disease progression in ALS, which occurs in both sporadic and genetic forms of ALS, with the majority caused by the mis-splicing of the KCNQ2 gene in the pre-mRNA. Kv7 is also a clinically validated target to regulate the hyperexcitable state in epilepsy. In vivo and in vitro studies have demonstrated that QRL-101 is more potent in threshold track studies and exhibits the potential for fewer clinical adverse events that ezogabine, a less selective, first-generation, Kv7.2/7.3 channel opener. The Phase 1 PoM study (QRL-101-05, NCT06681441) was a randomized, double-blind, placebo-controlled, three-way crossover trial. The study was conducted at the Centre for Human Drug Research, an early-phase Contract Research Organization based in Leiden, The Netherlands. The study evaluated two dose levels of QRL-101 versus placebo in healthy volunteers, assessing: Co-primary endpoints: Motor nerve excitability (mNETT SDTC; ALS biomarker) Cortical excitability (TMS-EMG MEP amplitude; epilepsy biomarker) Secondary endpoints: Additional TMS-EMG cortical excitability measures Resting-state pharmaco-EEG Safety, tolerability, and pharmacokinetics (PK) Additional QRL-101 clinical trials include: QRL-101-01 (NCT05667779) was a first-in-human, single-ascending dose clinical trial in 88 healthy participants. In this clinical trial, QRL-101 was shown to be well tolerated. The study completed in late 2023 and results from QRL-101-01 supported a tolerable dose range for subsequent studies. QRL-101-03 (NCT06532396) is a randomized, double-blind, placebo-controlled, multiple-ascending dose clinical trial evaluating the safety, tolerability, and PK of QRL-101 in up to 60 healthy participants. QRL-101-04 (NCT06714396) is a Phase 1 PoM single-dose, placebo-controlled clinical trial designed to evaluate the safety and tolerability of QRL-101 in people living with ALS. QRL-101-04 is expected to enroll approximately 12 participants with ALS and will evaluate the impact of QRL-101 on mNETT. QRL-101-06 is a Phase 1 randomized, open-label, single dose, cross-over study to evaluate the PK of three formulations of QRL-101 in a fasted condition or in the presence of a high fat meal in healthy participants. More information about the QRL-101 clinical trials can be found at . About QurAlis Corporation At QurAlis, we are neuro pioneers on a quest to cure, boldly seeking to translate scientific breakthroughs into powerful precision medicines. We work collaboratively with a relentless pursuit of knowledge, precise attention to craft, and compassion to discover and develop medicines that have the potential to transform the lives of people living with neurodegenerative and neurological diseases. QurAlis is the leader in development of precision therapies for amyotrophic lateral sclerosis (ALS). In addition to ALS, QurAlis is advancing a robust precision medicine pipeline to bring effective disease-modifying therapeutics to patients suffering from severe diseases defined by genetics and clinical biomarkers. For more information, please visit or follow us on X @QurAlisCo or LinkedIn. SOURCE QurAlis WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床1期临床结果

2025-02-06

·化学经纬

书籍分享||新药化学全合成路线手册

内容介绍本书归纳和综述了新药的化学合成路线。覆盖范围为近5年美国FDA批准上市的新分子实体药共109个。针对每一个药物，本书给出了药物简介，药物化学结构信息，产品上市信息，药品专利保护和市场独占权保护信息，化学全合成路线和参考文献等。这些合成路线大多是目前制药工业中正在使用的化学合成工艺，有较高的实用性和学术价值。对参与反应的起始原料、中间体、反应产物都给出了详细的化学结构。每一步化学合成反应都给出了重要的化学试剂、催化剂、所使用的溶剂、合成反应条件及文献出处等。本书的特点是：作者从浩如烟海的科技文献中，精心挑选出最新、最有实用价值的合成方法，汇编成化学合成路线图，内容简洁，深入浅出，逻辑性强，容易理解，以最少的篇幅表达最多的技术信息，可帮助读者很快找到他们需要的药物合成方法及最可靠的原始科学论文。读者对象： 1.任何从事与化学合成、药物合成、精细化工相关专业的科研人员、企业管理人员。 2.有机化学专业、药学专业、生物制药专业等大专院校的高年级学生、研究生、教师及科研人员。 3.从事客户委托的药物原料与药物中间体合成的科研人员、企业管理人员。编辑推荐对于制药企业而言,一个好的药物全合成路线, 可以大大缩短生产周期,简化生产工艺,降低生产成本,节约能源,减少或消除对环境的化学污染与排放。本书为了顺应我国近年来生物制药及医药工业飞速发展的潮流编写的，详细介绍了近五年美国FDA批准上市的所有（109个）新分子实体药的化学全合成路线。这些全合成路线多数是国外制药厂目前正在使用的工艺，其经济效益及社会效益都是极为显著，因此本书既有较高的科学价值又有很大的实用性。作者简介陈清奇，旅美药学家和化学家，担任美国MedKoo生物医药科研公司总裁，同时兼任美国数家生物制药公司的技术顾问，中国国内数个大学的客座教授。研究领域为药物化学，纳米医学体外诊断技术。书籍目录 Abiraterone Acetate（醋酸阿比特龙）001 Aclidinium Bromide（阿克利溴铵）006 Afatinib（阿法替尼）009 Alcaftadine（阿卡他定）014 Alogliptin（阿格列汀）017 Apixaban（阿哌沙班）022 Apremilast（阿普斯特）028 Avanafil（阿伐那非）033 Axitinib（阿西替尼）038 Azilsartan Kamedoxomil（阿齐沙坦酯钾盐）044 Bazedoxifene（巴多昔芬）048 Bedaquiline（贝达喹啉）053 Belinostat（贝利司他）060 Boceprevir（波西普韦）064 Bosutinib（博舒替尼）071 Cabozantinib（卡博替尼）075 Canagliflozin（卡格列净）078 Carfilzomib（卡非佐米）083 Ceftaroline Fosamil（头孢洛林酯）087 Ceftolozane（噻呋特啰嗪）094 Ceritinib（色瑞替尼）098 Clobazam（氯巴占）101 Cobicistat（可比司他）104 Crizotinib（克里唑蒂尼）112 Dabigatran Etexilate Mesylate（甲磺酸达比加群酯）118 Dabrafenib（达拉菲尼）123 Dapagliflozin（达格列净）127 Dasabuvir（达沙布韦）132 Deferiprone（去铁酮）136 Dienogest（地诺孕素）138 Dolutegravir（度鲁特韦）141 Droxidopa（屈昔多巴）145 Efinaconazole（艾氟康唑）149 Eliglustat（依利格鲁司特）152 Elvitegravir（埃替格韦）155 Empagliflozin（依帕列净）161 Enzalutamide（恩杂鲁胺）166 Eribulin Mesylate（甲磺酸艾日布林）168 Eslicarbazepine Acetate（艾利西平醋酸酯）175 Estradiol Valerate（雌二醇戊酸酯）180 Ezogabine（依佐加滨）185 Finafloxacin（非那沙星）193 Fingolimod Hydrochloride（盐酸芬戈莫德）197 Florbetapir F 18（氟比他匹）205 Flutemetamol F 18（富特米他）211 Gabapentin Enacarbil（加巴喷丁恩那卡比）214 Gadobutrol（钆布醇）218 Gadoterate Meglumine（钆特酸葡甲胺）224 Ibrutinib（依鲁替尼）227 Icatibant（艾替班特）232 Idelalisib（艾代拉里斯）234 Indacaterol （茚达特罗）236 Ingenol Mebutate（巨大戟醇甲基丁烯酸酯）240 Ioflupane 123I（碘[123I]氟潘）242 Ivacaftor（依瓦卡特）247 Ledipasvir（雷迪帕韦）250 Linaclotide（利那洛肽）259 Linagliptin（利拉利汀）261 Lomitapide（洛美他派）267 Lorcaserin（氯卡色林）270 Lucinactant（芦西纳坦）274 Luliconazole（卢立康唑）276 Lurasidone（鲁拉西酮）279 Macitentan（马西替坦）283 Miltefosine（米替福新）286 Mipomersen Sodium（米泊美生钠）290 Mirabegron（米拉贝隆）292 Naloxegol（纳罗克格）296 Netupitant（奈妥吡坦）299 Nintedanib（尼达尼布）303 Olaparib（奥拉帕尼）307 Olodaterol（奥达特罗）311 Omacetaxine Mepesuccinate（高三尖杉酯碱）315 Ombitasvir（艾姆伯韦）319 Ospemifene（奥培米芬）323 Paritaprevir（帕瑞它韦）327 Pasireotide（帕瑞肽）331 Peramivir（帕拉米韦）333 Perampanel（吡仑帕奈）337 Pirfenidone（吡非尼酮）343 Pomalidomide（泊马度胺）345 Ponatinib（泊那替尼）351 Regorafenib（瑞戈非尼）355 Rilpivirine（利匹韦林）357 Riociguat（利奥西呱）366 Rivaroxaban（利伐沙班）370 Roflumilast（罗氟司特）378 Ruxolitinib（鲁索替尼）384 Simeprevir（司美匹韦）388 Sofosbuvir（索非布韦）396 Suvorexant（苏沃雷生）401 Tafluprost（他氟前列腺素）405 Tasimelteon（他司美琼）409 Tavaborole（它瓦波罗）413 Tedizolid Phosphate（磷酸特地唑胺）415 Telaprevir（替拉瑞韦）418 Teriflunomide（特立氟胺）426 Ticagrelor（替格瑞洛）430 Tofacitinib（托法替尼）438 Trametinib（曲美替尼）443 Umeclidinium（芜地溴铵）447 Vandetanib（凡德他尼）450 Vemurafenib（威罗菲尼）456 Vilanterol（维兰特罗）460 Vilazodone Hydrochloride（盐酸维拉佐酮）463 Vismodegib（维莫德吉）468 Vorapaxar（沃拉帕沙）470 Vortioxetine（沃替西汀）473 附录1本书使用的期刊名称缩写表477 附录2专利文献代码481 附录3美国药品专利中的用途代码定义484 附录4美国药品市场独占权代码定义530 附录5美国FDA于2010—2014批准上市的药物名单563 英文索引607 中文索引611 CAS登记号索引613 下载方式现在，这份资料分享给大家。小编在公众号设置了自动回复功能，在公众号后台回复关键词：新药全合成 ●书籍分享||有机氧化反应原理与应用 ●书籍分享||有机卤化反应原理及应用 ●推荐合成书籍【有机缩合反应原理与应用】 ●推荐合成书籍【有机环合反应原理与应用】 ●书籍分享||有机还原反应原理与应用 ●ChemDraw使用让你从化学菜鸟变成老鸟 ●干货分享||有机合成: 策略与控制 ●干货分享||有机合成工艺研发-副反应抑制法 ●基础有机化学(邢其毅)第3、4版教材+习题解析 ●ChemDrawV20最新版详细安装图文教程 ●干货分享||核磁共振二维谱 ●书籍分享||全合成中的经典:更多的目标、战略和方法 ●书籍分享||实用药物化学 ●书籍分享||基于模仿创新的小分子药物发明 ●书籍分享||制药工艺开发-目前的化学与工程挑战 ●书籍分享||手性合成:不对称反应及其应用(第5版) ●书籍分享||新药研发案例研究--明星药物如何从实验室走向市场 ●书籍分享||英汉·汉英化学化工词汇 ●书籍分享||有机化学结构与功能（第四版） ●书籍分享||过渡金属有机化学(原著第6版） ●重磅书籍分享||不对称催化基础 ●书籍分享||药物设计学-唐赟

上市批准高管变更

2024-12-06

·PRNewswire

Biohaven Presents New Data with BHV-7000 Once-Daily Extended-Release Formulation Demonstrating Excellent Safety Profile and Nonclinical Data Updates at American Epilepsy Society 2024 Annual Meeting

Reported expanded safety results from BHV-7000 Phase 1 multiple ascending dose studies, including the once-daily extended-release formulation being evaluated in ongoing Phase 2 and 3 clinical studies, demonstrating excellent tolerability at all doses evaluated without central nervous system (CNS) adverse effects typically associated with other anti-seizure medications (ASMs), such as somnolence and cognitive/mood disturbances. Qualitative assessment of online social media platforms and forums provided a unique perspective of the unmet needs that people with epilepsy are vocalizing outside of the clinical setting, including the negative impact that ASM associated adverse events have on their quality of life. Additional nonclinical data presentations included characterization of BHV-7000 using optical electrophysiology as well as beneficial effects of BHV-7000 on pathogenic developmental epileptic encephalopathy-associated KCNQ2 variants NEW HAVEN, Conn., Dec. 6, 2024 /PRNewswire/ -- Biohaven Ltd. (NYSE: BHVN) announced today that it is presenting expanded safety data from BHV-7000 multiple-dose studies at the American Epilepsy Society (AES) 2024 Annual Meeting, taking place December 6-10, 2024, in Los Angeles, California. Additional poster presentations highlight BHV-7000 nonclinical data and unmet needs that persist for people living with epilepsy, including the negative impact of adverse effects associated with current ASMs. Jason Lerner, M.D., Medical Director and Epilepsy Clinical Lead at Biohaven, commented, "We are very excited to share the expanded safety results with the once-daily extended-release formulation being evaluated in ongoing Phase 2 and 3 clinical studies. We are encouraged to see BHV-7000 continue to demonstrate favorable safety and tolerability without dose-limiting toxicities or CNS adverse events commonly associated with other ASMs, such as somnolence. These results paired with previously demonstrated CNS target engagement in our Phase 1 EEG study and a nonclinical profile showing BHV-7000 is a selective Kv7.2/7.3 activator that dials out GABAA activation provide compelling rationale for why BHV-7000 offers a differentiated profile from other treatments currently available or in development." Dr. Lerner continued, "The evidence to date with BHV-7000 represents a potential paradigm shift in the treatment of epilepsy as many patients continue to be burdened by adverse events and do not achieve adequate seizure control with existing medications. As we continue advancing 5 ongoing pivotal Phase 2/3 trials with BHV-7000, including studies in focal epilepsy and idiopathic generalized epilepsy, Biohaven remains committed to developing novel, efficacious, and well-tolerated therapies for people living with epilepsy." In addition to 4 poster presentations at AES, Biohaven will be presenting 1 poster at the Partners Against Mortality (PAME) 2024 Conference in Los Angeles on Thursday, December 5th highlighting the patient-centric Phase 2/3 BHV-7000 study in idiopathic generalized epilepsy. American Epilepsy Society 2024 Annual Meeting Presentation Highlights: Poster 1.486: Phase 1 Multiple Ascending Dose Studies Demonstrate Safety and Tolerability of BHV-7000, a Novel Kv7 Potassium Channel Activator BHV-7000 is a selective Kv7.2/7.3 activator that was safe and well-tolerated at dose levels up to 120 mg daily for 15 days with no dose-limiting toxicities; 120 mg exceeds the doses being evaluated in ongoing Phase 2 and 3 clinical studies of up to 75 mg daily in focal epilepsy, idiopathic generalized epilepsy, bipolar mania, and major depressive disorder. There were low rates of CNS-related adverse events and no somnolence or cognitive/mood disturbances reported. Most AEs were mild and resolved spontaneously; and there were no serious adverse events or severe adverse events. New data with the BHV-7000 once-daily extended-release formulation demonstrated excellent tolerability. Poster 1.512: A Qualitative Assessment of the Epilepsy Patient Experience Through Social Media and Web-based Forums While seizure freedom remains the primary goal of epilepsy treatment, additional unmet needs of people living with epilepsy were assessed by investigating the patient experience directly through social media and online platforms where patients discuss epilepsy outside of a clinical setting. Patient perspectives and unmet needs were identified across 3 areas: antiseizure medication-associated adverse events, mental health, and stigma. The 4 most frequently discussed ASM associated adverse events included: sleepiness, insomnia, mood changes, and cognitive effects; comments from patients captured the negative impact these adverse events have on their quality of life. People with epilepsy also reported a range of challenges with mental health, and the stigma associated with epilepsy pressured patients to remain silent about their struggles. Poster 1.534: Pharmacological Characterization of BHV-7000, a Novel and Selective Activator of Kv7 Channels, Using All-optical Electrophysiology The acute and chronic pharmacological effects of BHV-7000 on the excitability of primary rat cortical neurons were evaluated using the all-optical electrophysiology platform Optopatch (Quiver Biosciences), which measures neuronal activity with single-cell and single action potential resolution. Concentration-dependent dampening of neuronal excitability was observed, consistent with previous data with BHV-7000 in other experimental paradigms. Overall, BHV-7000 demonstrated potent in vitro effects to reduce neuronal activity impacting a diverse set of Optopatch functional features across the stimulus protocol, including spike timing and spike shape features in different stimulus periods, which indicates lower neuronal excitability near action potential threshold. Poster 1.431: BHV-7000 Is a Potent M-current Activator with Efficacy on Multiple Epilepsy-associated KCNQ2 Variants This in vitro study assessed the effects of BHV-7000 on 50 loss-of-function KCNQ2 variants. BHV-7000 rescued current density in all tested pathogenic KCNQ2 variants. Current density was restored to wild-type (WT) levels with BHV-7000 for most variants. These findings support the potential therapeutic value of BHV-7000 in KCNQ2-related epilepsy associated with a wide range of pathogenic KCNQ2 variants. Partners Against Mortality (PAME) 2024 Conference Highlights: PAME Poster 41: A Modern Design for a Phase 2/3 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Efficacy and Safety of BHV-7000 in Idiopathic Generalized Epilepsy (IGE) With Generalized Tonic–Clonic Seizures (SHINE) Epilepsy studies have traditionally been double-blind, placebo-controlled, change-from-baseline endpoint studies; in these studies, subjects receiving placebo for a fixed treatment duration remain at risk for continued seizures, injury, and Sudden Unexpected Death in Epilepsy (SUDEP). SHINE (NCT06425159) is an innovative, ongoing registrational study in IGE with the selective Kv7 activator BHV-7000 with an efficient, patient-centric design utilizing an FDA-endorsed time to event endpoint that decreases time on placebo, potentially reducing the risk of exposure to additional seizures, injury, and SUDEP. Full posters will be available on the Posters and Presentations page at: . About BHV-7000 BHV-7000 is a novel and selective activator of Kv7.2/Kv7.3, a key ion channel involved in neuronal signaling and in regulating the hyperexcitable state, that is being developed for the treatment of epilepsy and mood disorders. BHV-7000 was rationally developed as a potent activator of heteromeric Kv7.2/7.3 potassium channels, the molecular substrate that underlies the M-current (IKM). BHV-7000 is highly differentiated from ezogabine (known as retigabine in Europe), a Kv7 activator that was previously approved for adjunctive treatment of partial-onset seizures in adults. In comparison with ezogabine, BHV-7000 belongs to a significantly different structural class and differentiates from ezogabine in key properties, including pharmacology, plasma stability and stability to photooxidation. In addition, BHV-7000 does not exhibit GABAA receptor positive allosteric molecular activity as seen with ezogabine and similar compounds, which may contribute to the poor tolerability of ezogabine. This lack of GABAA receptor activity may translate to improved tolerability by reducing the typical dose dependent side effect profile often seen in patients receiving ezogabine and other anti-seizure medications. About Biohaven Biohaven is a biopharmaceutical company focused on the discovery, development, and commercialization of life-changing treatments in key therapeutic areas, including immunology, neuroscience, and oncology. The company is advancing its innovative portfolio of therapeutics, leveraging its proven drug development experience and multiple proprietary drug development platforms. Biohaven's extensive clinical and nonclinical programs include Kv7 ion channel modulation for epilepsy and mood disorders; extracellular protein degradation for immunological diseases; TRPM3 antagonism for migraine and neuropathic pain; TYK2/JAK1 inhibition for neuroinflammatory disorders; glutamate modulation for OCD and SCA (spinocerebellar ataxia); myostatin inhibition for neuromuscular and metabolic diseases, including SMA and obesity; antibody recruiting bispecific molecules and antibody drug conjugates for cancer. For more information, visit . Forward-looking Statements This news release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. The use of certain words, including "continue", "plan", "will", "believe", "may", "expect", "anticipate" and similar expressions, is intended to identify forward-looking statements. Investors are cautioned that any forward-looking statements, including statements regarding the future development, timing and potential marketing approval and commercialization of development candidates, are not guarantees of future performance or results and involve substantial risks and uncertainties. Actual results, developments and events may differ materially from those in the forward-looking statements as a result of various factors including: the expected timing, commencement and outcomes of Biohaven's planned and ongoing clinical trials; the timing of planned interactions and filings with the FDA; the timing and outcome of expected regulatory filings; complying with applicable U.S. regulatory requirements; the potential commercialization of Biohaven's product candidates; and the effectiveness and safety of Biohaven's product candidates. Additional important factors to be considered in connection with forward-looking statements are described in Biohaven's filings with the Securities and Exchange Commission, including within the sections titled "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations". The forward-looking statements are made as of the date of this news release, and Biohaven does not undertake any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law. Investor Contact: Jennifer Porcelli Vice President, Investor Relations [email protected] +1 (201) 248-0741 Media Contact: Mike Beyer Sam Brown Inc. [email protected] +1 (312) 961-2502 SOURCE Biohaven Ltd. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床结果临床1期上市批准临床2期

100 项与瑞替加滨相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D09569	瑞替加滨	N03AX21	DB04953

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适应症	国家/地区	公司	日期
癫痫部分性发作	欧盟	Glaxo Group Ltd.	2011-03-27
癫痫部分性发作	冰岛	Glaxo Group Ltd.	2011-03-27
癫痫部分性发作	列支敦士登	Glaxo Group Ltd.	2011-03-27
癫痫部分性发作	挪威	Glaxo Group Ltd.	2011-03-27

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适应症	最高研发状态	国家/地区	公司	日期
癫痫综合征	临床3期	美国	Xenon Pharmaceuticals, Inc.	2021-03-29
癫痫综合征	临床3期	澳大利亚	Xenon Pharmaceuticals, Inc.	2021-03-29
癫痫综合征	临床3期	比利时	Xenon Pharmaceuticals, Inc.	2021-03-29
癫痫综合征	临床3期	意大利	Xenon Pharmaceuticals, Inc.	2021-03-29
癫痫综合征	临床3期	西班牙	Xenon Pharmaceuticals, Inc.	2021-03-29
KCNQ2相关性癫痫性脑病	临床3期	美国	Xenon Pharmaceuticals, Inc.	2021-03-29
KCNQ2相关性癫痫性脑病	临床3期	澳大利亚	Xenon Pharmaceuticals, Inc.	2021-03-29
KCNQ2相关性癫痫性脑病	临床3期	比利时	Xenon Pharmaceuticals, Inc.	2021-03-29
KCNQ2相关性癫痫性脑病	临床3期	意大利	Xenon Pharmaceuticals, Inc.	2021-03-29
KCNQ2相关性癫痫性脑病	临床3期	西班牙	Xenon Pharmaceuticals, Inc.	2021-03-29

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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


NCT04912856 (EPIK-OLE, CTgov)	临床3期	癫痫发作 \| KCNQ2相关性癫痫性脑病 \| 癫痫综合征	8	XEN496 (Group 1: XEN496 Treatment in Preceding Study)	選觸築鹽醖遞淵積夢廠 = 網觸廠艱範製淵鹽艱鏇製窪積鹽膚蓋製鏇壓築 (窪蓋窪蓋製簾糧齋鏇衊, 構鏇淵憲觸鏇範積壓壓 ~ 蓋襯鹹繭鏇夢鏇憲願簾) 更多	-	2025-03-25
				Placebo (Group 2: Placebo Treatment in Preceding Study)	選觸築鹽醖遞淵積夢廠 = 獵齋鏇鬱襯憲顧遞製簾製窪積鹽膚蓋製鏇壓築 (窪蓋窪蓋製簾糧齋鏇衊, 廠艱淵製選壓餘衊構繭 ~ 壓構積膚齋糧壓鏇選衊) 更多
NCT04639310 (EPIK, CTgov)	临床3期	癫痫发作 \| KCNQ2相关性癫痫性脑病 \| 癫痫综合征	8	XEN496 (XEN496)	蓋廠遞鬱範構齋壓積遞(窪窪憲壓網糧衊構遞範) = 鑰鬱鏇獵壓憲餘願鏇淵艱齋獵衊顧鏇艱餘鏇糧 (齋積廠獵願製鑰築遞獵, 23.49) 更多	-	2024-08-23
				Placebo (Placebo)	蓋廠遞鬱範構齋壓積遞(窪窪憲壓網糧衊構遞範) = 鏇願夢觸願鏇夢憲獵膚艱齋獵衊顧鏇艱餘鏇糧 (齋積廠獵願製鑰築遞獵, 46.84) 更多
NCT03043560 (CTgov)	临床2期	快感缺乏 \| 重度抑郁症	45	Ezogabine (Ezogabine)	鏇醖齋簾選廠窪醖憲蓋(觸製夢繭遞艱積積蓋膚) = 衊廠鏇繭膚襯鬱膚窪蓋襯鑰鬱鏇鏇鹹顧壓積襯 (遞顧觸憲觸觸壓顧鏇觸, 0.69) 更多	-	2020-10-23
				Placebos (Placebo)	鏇醖齋簾選廠窪醖憲蓋(觸製夢繭遞艱積積蓋膚) = 鹽構鬱顧選壓築鏇鹽觸襯鑰鬱鏇鏇鹹顧壓積襯 (遞顧觸憲觸觸壓顧鏇觸, 0.79) 更多
SFN2019	N/A	-	-	Retigabine	鏇齋製構衊醖壓醖範鏇(積廠壓壓衊憲積窪積範) = 餘範壓醖網糧築鹹淵鏇顧膚製鏇積鏇遞淵窪鏇 (壓鏇鑰醖鹽糧獵齋遞築 )	-	2019-10-21
				CPRET-46	鏇齋製構衊醖壓醖範鏇(積廠壓壓衊憲積窪積範) = 壓憲醖糧淵鹽鑰廠醖壓顧膚製鏇積鏇遞淵窪鏇 (壓鏇鑰醖鹽糧獵齋遞築 )
NCT02450552 (CTgov)	临床2期	肌萎缩侧索硬化	65	Ezogabine (Oral Ezogabine 900 mg/Day)	餘窪鬱積艱壓廠願衊壓(壓夢製範鬱範齋鑰衊網) = 醖襯製醖廠糧獵獵積獵鹽膚網鏇鑰築簾淵簾淵 (衊憲廠構窪憲廠繭顧範, 1.108) 更多	-	2019-08-28
				Ezogabine (Oral Ezogabine 600 mg/Day)	餘窪鬱積艱壓廠願衊壓(壓夢製範鬱範齋鑰衊網) = 膚襯鹹憲鏇鏇淵獵鏇淵鹽膚網鏇鑰築簾淵簾淵 (衊憲廠構窪憲廠繭顧範, 1.302) 更多
NCT01777139 (CTgov)	临床3期	癫痫发作 \| 癫痫	30	Retigabine IR	衊夢齋製鏇願獵構鹽鏇(壓鬱繭願簾醖艱膚鑰膚) = 顧鹽鹽簾選餘遞餘糧蓋膚鹽築獵壓淵蓋獵網衊 (遞淵鬱鹹獵遞鬱鑰齋鏇, 2.68) 更多	-	2019-04-22
NCT02149836 (CTgov)	临床2期	中度重度抑郁症 \| 重度抑郁症	18	ezogabine	願蓋製鹽簾鑰憲選築蓋(糧願膚觸觸膚蓋簾窪選) = 衊壓糧鏇構醖製齋襯鹹壓積築鏇醖鑰壓憲壓繭 (遞鏇願廠鏇壓壓觸窪壓, 4.93) 更多	-	2019-04-16
Retigabine and Mexiletine-2 Studies (AAN2019)	N/A	肌萎缩侧索硬化	138	Retigabine	夢願壓襯顧鬱積膚壓積(壓構願餘網獵淵鑰膚積) = 遞網夢衊築醖遞窪憲範夢繭襯襯鹽願鏇夢選網 (醖鏇衊鬱衊繭選觸簾築, 37.5) 更多	-	2019-04-09
				Retigabine	夢願壓襯顧鬱積膚壓積(壓構願餘網獵淵鑰膚積) = 夢簾築憲遞築壓壓積製夢繭襯襯鹽願鏇夢選網 (醖鏇衊鬱衊繭選觸簾築, 46.7) 更多
NCT00310388 (CTgov)	临床3期	癫痫部分性发作	376	Retigabine (Retigabine)	構製鏇製鏇淵鹽糧觸壓 = 艱鏇夢獵範糧餘鏇範鹹壓築鏇蓋憲糧鬱壓範壓 (艱齋衊憲範獵糧鹹糧鏇, 積願繭窪艱鹽艱繭壓遞 ~ 鏇鹽簾醖憲積簾夢繭淵) 更多	-	2018-06-06
				retigabine (SFUCP)	鬱鏇襯襯鹽夢網衊選膚 = 鑰鏇願構鬱蓋繭壓鹹窪憲齋鏇顧顧鬱觸淵構鬱 (夢繭鹹築淵糧憲餘顧衊, 觸選壓願糧醖淵醖餘蓋 ~ 襯願襯衊簾鑰襯憲糧餘) 更多
NCT01336621 (IR, CTgov)	临床3期	癫痫发作 \| 癫痫部分性发作	98	Retigabine IR	鹽觸蓋衊醖鏇鏇鏇齋製 = 選窪鏇鏇顧壓憲網餘糧壓廠築廠糧觸壓醖選網 (醖鏇窪鑰簾壓獵廠蓋顧, 構窪鹹鏇觸築淵選製艱 ~ 衊醖醖餘遞淵鬱製鹹範) 更多	-	2018-02-26