本研究（即核心期）的目的是在H1抗组胺药（H1-AH）控制不佳的12至 < 18岁慢性自发性荨麻疹青少年患者中评估remibrutinib（LOU064）vs. 安慰剂的疗效、药代动力学和安全性。开放性扩展（OLE）期的目的是收集完成核心期（即24周治疗）后的青少年接受remibrutinib治疗的长期疗效、安全性和耐受性数据。诺华还将通过该扩展期履行承诺，即为参加前一个核心期的受试者提供试验后供药。长期无治疗随访（LTTFFU）期的目的是收集该人群在OLE 期接受末次治疗后最长3年的安全性数据。

开始日期2024-05-07

申办/合作机构

诺华（中国）生物医学研究有限公司

CTR20240112 / Recruiting临床3期

一项评价remibrutinib（LOU064）在H1抗组胺药控制不佳的慢性诱导性荨麻疹（CINDU）成人患者中治疗52周的疗效、安全性和耐受性的多中心、随机、双盲、安慰剂对照、篮式研究（含开放性扩展期）

本研究的目的是评价remibrutinib相比安慰剂治疗H1抗组胺药控制不佳的CINDU成人患者的疗效、安全性和耐受性。

开始日期2024-03-26

申办/合作机构

诺华（中国）生物医学研究有限公司

CTRI/2024/01/061150 / Recruiting临床3期

A multicenter, double-blind, placebo-controlled, randomized withdrawal and open-label extension study followed by long-term open-label treatment cycles to assess the efficacy, safety and tolerability of remibrutinib (LOU064) in adult chronic spontaneous urticaria patients who completed the preceding remibrutinib Phase 3 studies. - LOU064 Roll over

开始日期2024-02-05

申办/合作机构

Novartis Healthcare Pvt Ltd.

100 项与 Remibrutinib 相关的临床结果

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100 项与 Remibrutinib 相关的转化医学

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100 项与 Remibrutinib 相关的专利（医药）

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项与 Remibrutinib 相关的文献（医药）

2024-03-01·Annals of the rheumatic diseases

Efficacy and safety of remibrutinib, a selective potent oral BTK inhibitor, in Sjögren’s syndrome: results from a randomised, double-blind, placebo-controlled phase 2 trial

Article

作者: Cenni, Bruno ; Kaul, Martin ; Hanser, Malika ; Papas, Athena S ; Grioni, Andrea ; Gergely, Peter ; Tseng, Jui-Cheng ; Szántó, Antónia ; Pylvaenaeinen, Ilona ; Hillenbrand, Rainer ; Ferrero, Enrico ; Abdallah, Nasri ; Avrameas, Alexandre ; Siegel, Richard M ; Dörner, Thomas ; Santos Da Costa, Aida

Objectives:

To evaluate the safety and efficacy of remibrutinib in patients with moderate-to-severe Sjögren’s syndrome (SjS) in a phase 2 randomised, double-blind trial (NCT04035668; LOUiSSE (LOU064 in Sjögren’s Syndrome) study).

Methods:

Eligible patients fulfilling 2016 American College of Rheumatology/European League Against Rheumatism (EULAR) criteria for SjS, positive for anti-Ro/Sjögren’s syndrome-related antigen A antibodies, with moderate-to-severe disease activity (EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) (based on weighted score) ≥ 5, EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) ≥ 5) received remibrutinib (100 mg) either one or two times a day, or placebo for the 24-week study treatment period. The primary endpoint was change from baseline in ESSDAI at week 24. Key secondary endpoints included change from baseline in ESSDAI over time, change from baseline in ESSPRI over time and safety of remibrutinib in SjS. Key exploratory endpoints included changes to the salivary flow rate, soluble biomarkers, blood transcriptomic and serum proteomic profiles.

Results:

Remibrutinib significantly improved ESSDAI score in patients with SjS over 24 weeks compared with placebo (ΔESSDAI −2.86, p=0.003). No treatment effect was observed in ESSPRI score (ΔESSPRI 0.17, p=0.663). There was a trend towards improvement of unstimulated salivary flow with remibrutinib compared with placebo over 24 weeks. Remibrutinib had a favourable safety profile in patients with SjS over 24 weeks. Remibrutinib induced significant changes in gene expression in blood, and serum protein abundance compared with placebo.

Conclusions:

These data show preliminary efficacy and favourable safety of remibrutinib in a phase 2 trial for SjS.

2023-12-01·Biomedical chromatography : BMC

Metabolite profiling of remibrutinib in rat and human liver microsomes using liquid chromatography combined with benchtop orbitrap high‐resolution mass spectrometry

Article

作者: Lu, Lingpan ; Li, Wenyuan ; Liu, Jinhai ; Qiu, Mingheng ; Qiao, Min ; Lai, Xinxin

Abstract:

Remibrutinib is a potent and highly selective covalent Bruton's tyrosine kinase inhibitor that is undergoing clinical development for the treatment of autoimmune diseases. The present study was undertaken to investigate the in vitro metabolism of remibrutinib and to propose its biotransformation pathways. The metabolites were generated by incubating remibrutinib (2 μm) with human and rat liver microsomes at 37°C for 30 min. Ultra‐high‐performance liquid chromatography combined with benchtop orbitrap high‐resolution mass spectrometry was used to identify and characterize the metabolites of remibrutinib. Compound Discoverer software was employed to process the acquired data. In rat liver microsomes, a total of 18 metabolites have been identified and characterized among which three (M8, M12 and M13) were identified as the most abundant metabolites. In human liver microsomes, a total of 16 metabolites have been identified, and M8 and M12 were identified as the predominant metabolites. All the metabolites were nicotinamide adenine dinucleotide phosphate dependent. The major metabolic changes were found to be oxygenation, dealkylation, demethylation, epoxidation and hydrolysis. The present study comprehensively reports the in vitro metabolism of remibrutinib mentioning 20 metabolites. These findings will help investigation of remibrutinib disposition and safety evaluation.

2023-12-01·The Journal of allergy and clinical immunology

BTK signaling—a crucial link in the pathophysiology of chronic spontaneous urticaria

Review

作者: Maurer, Marcus ; Saini, Sarbjit S ; Bernstein, Jonathan A

Chronic spontaneous urticaria (CSU) is an inflammatory skin disorder that manifests with itchy wheals, angioedema, or both for more than 6 weeks. Mast cells and basophils are the key pathogenic drivers of CSU; their activation results in histamine and cytokine release with subsequent dermal inflammation. Two overlapping mechanisms of mast cell and basophil activation have been proposed in CSU: type I autoimmunity, also called autoallergy, which is mediated via IgE against various autoallergens, and type IIb autoimmunity, which is mediated predominantly via IgG directed against the IgE receptor FcεRI or FcεRI-bound IgE. Both mechanisms involve cross-linking of FcεRI and activation of downstream signaling pathways, and they may co-occur in the same patient. In addition, B-cell receptor signaling has been postulated to play a key role in CSU by generating autoreactive B cells and autoantibody production. A cornerstone of FcεRI and B-cell receptor signaling is Bruton tyrosine kinase (BTK), making BTK inhibition a clear therapeutic target in CSU. The potential application of early-generation BTK inhibitors, including ibrutinib, in allergic and autoimmune diseases is limited owing to their unfavorable benefit-risk profile. However, novel BTK inhibitors with improved selectivity and safety profiles have been developed and are under clinical investigation in autoimmune diseases, including CSU. In phase 2 trials, the BTK inhibitors remibrutinib and fenebrutinib have demonstrated rapid and sustained improvements in CSU disease activity. With phase 3 studies of remibrutinib ongoing, it is hoped that BTK inhibitors will present an effective, well-tolerated option for patients with antihistamine-refractory CSU, a phenotype that presents a considerable clinical challenge.

项与 Remibrutinib 相关的新闻（医药）

2024-06-03

·E药经理人

152亿！强生“提刀”杀入“自免一哥”抢位赛！与诺华赛诺菲艾伯维相互“围剿”，谁赢？

当下，自身免疫赛道成为了商业化端群雄逐鹿、研发端龙争虎斗的新高地。撰文| 润屿撰文| 顿河芳晨刚过去的5月，数笔大并购带来了一个极为关键的信号：药企“诸神之战”，已正式转移至了自免领域。全球营收NO.1的强生“提刀”杀入，不到半个月时间狂掷152亿收购自免资产。渤健完成超10亿美元并购，目的在于用一个在肿瘤界必争的靶点CD38，去开发自免适应证。 2023年畅销药TOP10排位赛上，销售额排名前六的产品中，有一半来自自免领域，强生、赛诺菲与艾伯维之间暗流涌动。礼来等MNC正探索PD-1在自免领域的价值，CAR-T也开始拥抱自免赛道、“自免CAR-T第一股”已以较大募资规模登陆纳斯达克…… 从MNC的明争暗逐，到资本的看好，自免已成为众兵家必争之地。而在这场大战中，最精彩的莫过于：艾伯维、赛诺菲、强生、诺华都在称自己为“自免一哥”。到底谁是真正的“一哥”？“四强”纷纷把拿手好戏搬上了舞台。 “一哥”之辩自免舞台，“四强”登场，率先开启了一场口头上的“博弈”。刚刚先后以8.5亿美元现金和12.5亿美元收购了两家自免Biotech的强生，直接点燃导火索，称最新收购的自免产品与赛诺菲/再生元的度普利尤单抗，以及与艾伯维乌帕替尼比起来，或更具独特优势，且能治疗更多适应证。赛诺菲、艾伯维表面淡定，但或许内心在想：你的自免业务只是曾经辉煌，但现在，请在自免板块收入上先打败我再说。谈到自免领域收入，艾伯维率先会心一笑。即使药王修美乐专利到期，但2023年仍旧无人超越它在自免领域的吸金能力。艾伯维的“出战”语录是：请记住，我只培养冠军。曾经的修美乐可以统领一个时代，现在的Skyrizi（瑞莎珠单抗）和乌帕替尼，是绝对的种子选手。“自免一哥”非我莫属。但听到艾伯维的这一番发言，赛诺菲不干了：别老药新药一起算，全球TNF-α抑制剂整体销售已经疲软，度普利尤单抗才是自免新靶点核心药物中最畅销的。而且不是我骄傲，度普利尤单抗是我们推出的第一个免疫学药物，如此成绩，不配一个“一哥”头衔？这时，在一角坐观竞争的诺华站了起来：能担“一哥”者，考验的是破冰的胆量和能力。司库奇尤单抗一路用“头对头”试验，PK掉了其他银屑病玩家。关键是，我还能在一度“冰封”的中国自免创新药市场，把这一产品卖到最好，让中国的自免赛道被点燃。前者修美乐没能做起来，而后续进入中国的自免新药复刻我的曲线。另外，我们的自免管线数量布局，也是数一数二的。整体来看，艾伯维、强生、诺华、赛诺菲的强劲增长动力，均以自免药物为支撑，而四家MNC在自免领域各有优势。但从自免业务收入、上市药物销售额、研发布局力度和丰富度、以及技术积累与积淀等各个细分维度来看，“自免一哥”在各自的语境里，早已称王。难分伯仲论当下自免业务整体收入，艾伯维还是妥妥的“一哥”。2023年，一款老药修美乐，加上“双子星”——乌帕替尼和Skyrizi，三个产品创造了260亿美元的营收。即使赛诺菲和诺华两者自免业务（按主要产品来算）合力对打还是打不过。但论单个产品收入，最亮眼的不是艾伯维，反倒是赛诺菲。赛诺菲IL-4R产品度普利尤单抗，是全球首个治疗中重度特应性皮炎（AD）的生物制剂。2023年，度普利尤单抗大卖115.57亿美元，在十大畅销药中排名第五。这款药的存在，首先证明了IL-4Rα单抗在中重度AD系统治疗靶向药中最具综合优势，无论是能覆盖的人群、2型炎症，还是安全性；再是凭一举之力奠定了赛诺菲在自免领域的地位。最关键的，这款药是新靶点自免药物中，目前最畅销的一款。论积淀，强生是 “老大哥”。手握四张“王牌”的强生，其自免创新产品商业化之旅比艾伯维早了好几年。TNF-a抑制剂英夫利昔单抗是全球上市最早的两大自免产品之一，另外，还有百亿美元炸弹乌司奴单抗、Tremfya（古塞奇尤单抗）和Simponi（戈利木单抗）三大自免产品。2023年，尽管强生最大的产品亮点已转移至肿瘤领域，然而从营收贡献来看，自免仍是其第一大业务板块，总收入在180亿美元。论自免领域研发战略布局最妥当、产品接力节奏最为紧密的，是诺华。在全球，诺华司库奇尤单抗是销售额达50亿美元的重磅炸弹，在银屑病治疗领域，该产品通过一连串的“头对头”临床试验，PK掉了一众对手。海外多项头对头临床试验数据显示，IL-17 单抗产品司库奇尤单抗，优于辉瑞/安进的依那西普（TNF-α 单抗）和强生乌司奴单抗（IL-12/23 单抗）。目前，司库奇尤单抗治疗化脓性汗腺炎（HS）适应证在美国FDA及欧盟均已获批；重磅在研BTK抑制剂remibrutinib关于治疗慢性自发性荨麻疹（CSU）患者的III期临床试验在近日公布了积极数据，诺华打算自今年下半年开始向全球监管单位提交remibrutinib用于CSU的批准申请；在干燥综合征领域，诺华抗B细胞活化因子受体（BAFF-R）全人源单克隆抗体Ianalumab（VAY736）也是目前全球进展最快，且唯一进入临床III期的靶向BAFF-R抑制剂。而论管线布局，“自免”标签最鲜明的，是艾伯维和赛诺菲。前者梦想囊获自免多个子赛道“大满贯”，后者紧握手里的自免王牌，正在筹谋一盘自免大棋。但两者夯实自免领域实力的路径和阶段都不一样。艾伯维继续坚持采用“爆款策略”，当修美乐遭遇专利悬崖危机时，已巧妙找到了接下来的高增长引擎：口服JAK1抑制剂乌帕替尼和IL-23单抗Skyrizi（瑞莎珠单抗），艾伯维预计两者2027年合计收入将达到270亿美元。尤其是Skyrizi，有望成为第二个百亿“药王”，自2019年全球首次获批之后，基本上以50%左右的年增长率迅速放量。两大产品的适应证布局与拓展之快，而且艾伯维对其进行了银屑病和特应性皮炎等多个大适应证的“头对头”研究，并挑战成功。赛诺菲尚且还在度普利尤单抗大单品“上分”时代。但2024年及未来，赛诺菲将聚焦于自免领域展开布局版图。 “一哥”之战背后产品PK，市场之争，“一哥”之战背后，整个自免赛道被赋予了前所未有的“生命力”。 2023年，从所有畅销药营收来看，自免领域创新药的销售体量，已十分接近于肿瘤领域。但不论从患者规模、用药周期，还是从渗透率来讲，自免都还是一个等待被挖掘的超级蓝海赛道，有着广泛未被激活的市场需求，这一赛道几乎占据了所有能够诞生重磅炸弹药物的必备因素：患者基数大、生存期长、用药时间长，一个领域包含百余种不同疾病。而且难得的是，尽管TNF-α抑制剂一类自免药物销售增速集体趋缓，但近7年，以IL-23、IL-17、JAK、IL4/13 等新靶点重磅药物，其销售集体以高增长态势，展现出了自免赛道独特的“魅力”，且为中国的自免市场引入活力与生机。典型如诺华的司库奇尤单抗。兴业证券显示，司库奇尤单抗在诺华的强力推动下，在国内2020年、2021年、2022年的销售额分别约5亿元、15亿元和45亿元，占据了国内银屑病生物制剂的主要市场份额，国内银屑患者对于IL-17单抗熟悉度最高。而“自免四强”在激烈竞争过程中，其实机遇和危机并存，“青黄不接”等风险正倒逼他们通过并购、BD等方式，打造更多自免后备军和全新想象力，这再度为自免行业的快速发展，带来了“刺激”。强生是最典型的例子，作为业内“老大哥”，他同时面临着核心产品专利到期、FIC产品在遭遇“头对头”挑战后棋逢对手等问题。但在本月，强生已经在焦虑之下，彰显了大闯自免新路的决心。 2023年，强生自免板块业务占比有所下滑。英夫利昔单抗销售额降幅尤其严重；古赛奇尤单抗身处于IL-23抑制剂这一天花板自免赛道，但作为全球首款IL-23单抗药物，其在2023年增速放缓；乌司奴单抗终于突破百亿美元门槛，但其在美国的主要专利正式在2023年到期。作为核心自免上市产品最丰富、积淀最深的MNC，强生有些急于找回自免高地。于是，2024年，强生的新突破口，定在了进军中重度特应性皮炎和中重度哮喘治疗领域，同时，发挥其打造双抗产品的优势。 5月17日，强生收购自免双抗疗法公司 Proteologix，囊获一款靶向 IL-13 和 TSLP 的双抗，用于治疗中重度特应性皮炎和中重度哮喘，以及另一款靶向 IL-13 和 IL-22 的双抗产品，也用于治疗中重度特应性皮炎。5 月 28 日，强生再度宣布收购另一家自免Biotech，后者的核心资产仍旧双抗药物，适应证同样面向特应性皮炎。但双抗自免产品，能行吗？还需要最终验证。另外，努力打造下一个“药王”的艾伯维，同样也有些焦虑。艾伯维营收主要来源于五大疾病领域，但自免占据了绝对的收入大头。虽然Skyrizi和乌帕替尼大有修美乐接班者之势，但要实现自免“全满贯”，还得继续填补后备力量，同时坚守好爆款专利。今年以来，艾伯维不止一次与免疫治疗公司达成合作，寻找FIC产品。回复“V”，了解电子期刊详情精彩推荐 CM10 | 集采 | 国谈 | 医保动态 | 药审 | 人才 | 薪资 | 榜单 | CAR-T | PD-1 | mRNA | 单抗 | 商业化 | 国际化｜猎药人系列专题 | 出海启思会 | 声音·责任 | 创百汇 | E药经理人理事会 | 微解药直播 | 大国新药 | 营销硬观点 | 投资人去哪儿 | 分析师看赛道 | 药事每周谈 | 医药界·E药经理人 | 中国医药手册创新100强榜单 | 恒瑞 | 中国生物制药 | 百济 | 石药 | 信达 | 君实 | 复宏汉霖｜翰森 | 康方生物 | 上海医药 | 和黄医药 | 东阳光药 | 荣昌 | 亚盛医药 | 齐鲁制药 | 康宁杰瑞 | 贝达药业 | 微芯生物 | 复星医药｜再鼎医药｜亚虹医药跨国药企50强榜单 | 辉瑞 | 艾伯维 | 诺华 | 强生 | 罗氏 | BMS | 默克 | 赛诺菲 | AZ | GSK | 武田 | 吉利德科学 | 礼来 | 安进 | 诺和诺德 | 拜耳 | 莫德纳 | BI | 晖致 | 再生元

并购免疫疗法细胞疗法专利到期

2024-06-02

·药明康德

一周见效，疗效持续一年！诺华潜在“first-in-class”小分子抑制剂3期积极数据公布

▎药明康德内容团队编辑日前，诺华（Novartis）公布关键3期REMIX-1和REMIX-2试验的最新长期疗效数据，这两项试验评估其在研布鲁顿酪氨酸激酶（BTK）抑制剂remibrutinib在H1抗组胺药不能充分控制症状的慢性自发性荨麻疹（CSU）患者中的疗效与安全性。分析显示，患者最早在接受remibrutinib治疗一周后其CSU症状便获得改善，并持续至52周。诺华打算自2024年下半年开始向全球监管单位提交remibrutinib用于CSU的批准申请，并继续检视该药物用于治疗多种免疫介导疾病的作用。慢性自发性荨麻疹是一种难以预测的严重皮肤疾病，影响0.5-1%的全球人群。其特征为出现瘙痒、疼痛性荨麻疹、或/和肿胀，持续至少6周，且发生原因未知。由于CSU的严重程度和不可预测性，对患者的生活质量造成严重影响。H1抗组胺药是CSU的一线治疗药物，然而约60%患者的症状通过单用抗组胺药的控制结果不佳，在用药后持续存在CSU症状。BTK是组胺释放的核心酶，当自发激活时，在CSU相关的衰弱症状中起关键作用。在试验第52周所评估的最新3期REMIX-1和REMIX-2长期数据显示：如同之前第12周的数据，在第24周时，remibrutinib与安慰剂相比显著改善患者症状，包括在每周荨麻疹活动评分（UAS7）、每周瘙痒严重程度评分（ISS7）和每周荨麻疹严重程度评分（HSS7）上皆有所改善。第24周时，接受安慰剂治疗的患者转换为接受remibrutinib治疗；患者最早在转换药物后第1周观察到疾病缓解，并持续至研究结束（治疗28周）。根据第52周的评估，几乎一半的患者完全无瘙痒和荨麻疹症状（UAS7=0）。Remibrutinib的耐受性良好，并在长达52周的时间内表现出有利和一致的安全性特征。▲Remibrutinib分子结构式（图片来源：PubChem）Remibrutinib是一种潜在“first-in-class”的高选择性、口服BTK抑制剂，可阻断BTK级联反应，并阻止组胺释放引起的瘙痒、荨麻疹/伤痕和肿胀。它在几种免疫介导的疾病中显示出良好的安全性特征，包括多发性硬化、化脓性汗腺炎和食物过敏。▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料：[1] Novartis Phase III data confirm sustained efficacy and long-term safety of oral remibrutinib in chronic spontaneous urticaria. Retrieved May 31, 2024 from https://www.globenewswire.com/news-release/2024/05/30/2891212/0/en/Novartis-Phase-III-data-confirm-sustained-efficacy-and-long-term-safety-of-oral-remibrutinib-in-chronic-spontaneous-urticaria.html免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

临床3期临床结果上市批准临床成功

2024-05-31

·GlobeNewswire-Health Care

Novartis Phase III data confirm sustained efficacy and long-term safety of oral remibrutinib in chronic spontaneous urticaria

Patients treated with remibrutinib experienced improvements in weekly urticaria activity scores (UAS7) observed as early as Week 1 and sustained to 1 year (Week 52)1 Remibrutinib, an oral Bruton’s tyrosine kinase inhibitor, demonstrated a favorable and consistent safety profile up to 1 year, including balanced liver function tests versus placebo1 Novartis intends to submit remibrutinib for approval in chronic spontaneous urticaria (CSU) to global health authorities starting in H2 2024, and continues to investigate remibrutinib in multiple immune-mediated conditions Data reaffirm the first-in-class potential of remibrutinib for the more than 50% of patients with CSU uncontrolled by H1-antihistamines who continue to live with painful and debilitating symptoms1,2 May 31, 2024 – Novartis today announced new data that confirm the long-term efficacy and safety of remibrutinib, a highly selective Bruton’s tyrosine kinase (BTK) inhibitor, in chronic spontaneous urticaria (CSU)1. In the pivotal Phase III studies, REMIX-1 and REMIX-2, remibrutinib treatment showed significant symptom improvement early, which was sustained up to Week 52, in patients with CSU who remained symptomatic despite second-generation H1-antihistamine use1. These data are being presented at the 2024 European Academy of Allergy and Clinical Immunology (EAACI) Congress in Valencia, Spain, May 31–June 3. “A large majority of people with CSU are living with uncontrolled and debilitating symptoms, often trying to manage the condition by cycling through antihistamines at higher doses with no lasting respite, impacting heavily on their day-to-day lives,” said Martin Metz, Professor of Dermatology, Charité – Universitätsmedizin Berlin, Germany. “Remibrutinib has become an important investigational treatment for CSU as it blocks the BTK cascade and inhibits the release of histamine. These data show that remibrutinib has the potential to offer patients and physicians a well-tolerated oral treatment that provides early and lasting efficacy.” New long-term Phase III REMIX-1 and REMIX-2 data assessed at Week 52 show that1: Significant improvements with remibrutinib versus placebo, as previously shown at Week 12, were confirmed at Week 24, including in weekly urticaria activity score (UAS7), weekly itch severity score (ISS7), and weekly hive severity score (HSS7) At Week 24, patients receiving placebo were transitioned to remibrutinib; responses with remibrutinib were observed as early as the first week after switching and were sustained until the end of the study (28 weeks of treatment) Almost half of patients were completely free of itch and hives (UAS7=0) as assessed at Week 52 “Living with CSU can be very distressing due to its unpredictable nature and never knowing when a flare-up may happen. Symptoms can occur on the face, throat, hands, and feet, and people may experience burning and pain on their skin,” said Tonya Winders, President and CEO, Global Allergy and Airways Patient Platform. “Unfortunately, many people continue to cope with uncontrolled symptoms. We welcome further research advancing our knowledge about chronic spontaneous urticaria.” Remibrutinib was well-tolerated and demonstrated a favorable and consistent safety profile up to 52 weeks, including balanced liver function tests versus placebo1. Adverse events (AEs), including serious AEs and treatment discontinuations due to AEs, were comparable between remibrutinib and placebo during the 24-week placebo-controlled period1. In addition, exposure-adjusted rates did not increase with long-term treatment1. Liver transaminase elevations were balanced across the remibrutinib and placebo treatment groups; all were asymptomatic, transient, and reversible1. None of the serious AEs were considered related to study medication by investigators. “Urticaria is a disease that significantly impacts patients' quality of life and there is an urgent need for new treatment options,” said Angelika Jahreis, Global Head, Development, Immunology, Novartis. “The 52-week REMIX-1 and REMIX-2 Phase III data are significant as many patients who had moderate to severe urticaria at study start were completely free of itch and hives after 52 weeks of treatment and remibrutinib, a highly selective oral BTK inhibitor, continued to be well tolerated. These exciting long-term data will be submitted to global health authorities later this year.” In addition to CSU, remibrutinib is being investigated in several other immune-mediated conditions, such as hidradenitis suppurativa, where it met its primary endpoint in a Phase II study3. It is also being investigated in food allergy, chronic inducible urticaria, and multiple sclerosis4-8. Novartis will submit remibrutinib for approval in CSU to global health authorities starting in H2 2024. Remibrutinib is an investigational, highly selective, covalent, oral BTK inhibitor that blocks the BTK cascade and prevents the release of histamine that causes itchy hives (wheals) and swelling9-11. When remibrutinib is used alongside standard-dose antihistamines, it results in a “two-pronged approach” where two parts of the inflammatory pathway are targeted, with remibrutinib inhibiting histamine release and antihistamines inhibiting histamine receptors, reducing CSU symptoms12,13. In the pivotal Phase III studies, REMIX-1 and REMIX-2, remibrutinib met all primary endpoints in patients with CSU who remained symptomatic despite second-generation H1-antihistamine use1. Treatment with remibrutinib showed significant symptom improvement early, which was sustained up to Week 521. Remibrutinib has been shown to be well-tolerated, with a favorable safety profile up to 52 weeks, including balanced liver function tests versus placebo1. Most commonly (≥5%) observed AEs in the Phase III REMIX studies were respiratory tract infections (including COVID-19 and nasopharyngitis) and headache, all comparable with placebo1,14. If approved in CSU, remibrutinib would offer an effective oral option within the Novartis immunology portfolio, which currently includes Xolair® (omalizumab), the first and only injectable biologic indicated for CSU15. In the US, Novartis Pharmaceuticals Corporation and Genentech, a member of the Roche Group, work together to develop and co-promote Xolair. In addition to CSU, remibrutinib is being investigated in several other immune-mediated conditions and has the potential to be a pipeline in a product4-8. REMIX-1 (NCT05030311) and REMIX-2 (NCT05032157) are two identically designed, global, multicenter, randomized, double-blind, parallel-group, placebo-controlled Phase III studies, with REMIX-1 consisting of 470 participants and REMIX-2 consisting of 455 participants16,17. Both studies are designed to establish the efficacy, safety, and tolerability of twice-daily remibrutinib 25 mg treatment in adult participants with CSU that is inadequately controlled by second-generation H1-antihistamines compared with placebo1,16,17. The primary outcome measures were absolute change from baseline in weekly urticaria activity score (UAS7) as well as weekly itch severity score (ISS7) and weekly hive severity score (HSS7) at Week 1216,17. All participants were on a stable, local label-approved dose of a second-generation H1-antihistamine throughout the entire study16,17. CSU is the medical term for chronic hives that last for 6 weeks or longer, where the underlying cause is internal rather than exposure to any allergen or external trigger2,11,18. CSU affects approximately 40 million people worldwide2,19. It is characterized by the sudden appearance of itchy hives (wheals) and/or deep tissue swelling (angioedema, which can occur on the face, throat, hands, and feet)11,20. CSU affects all ages but occurs most frequently between the ages of 20–40 years, with women affected nearly twice as often as men2. CSU causes significant emotional distress, with the majority of patients suffering from sleep deprivation, and high rates of mental disorders, such as anxiety or depression, as well as impacting on their work productivity2. Antihistamines are often prescribed for CSU as they block histamine receptors and prevent the pro-inflammatory action of histamine, which causes itching and swelling13,18. However, more than 50% of people with CSU are uncontrolled by H1-antihistamines alone2. Novartis is an innovative medicines company. Every day, we work to reimagine medicine to improve and extend people’s lives so that patients, healthcare professionals and societies are empowered in the face of serious disease. Our medicines reach more than 250 million people worldwide. References Metz M, Giménez-Arnau A, Hide M, et al. Long-term efficacy and safety of remibrutinib in patients with chronic spontaneous urticaria in the Phase 3 REMIX-1 and REMIX-2 studies. Presented as a late oral abstract session on clinical trials at EAACI 2024; May 31-June 3, 2024; Valencia, Spain. Maurer M, Weller K, Bindslev-Jensen C, et al. Unmet clinical needs in chronic spontaneous urticaria. A GA²LEN task force report. Allergy 2011; 66: 317-330. Kimball A, Prens E, Bechara F, et al. Efficacy and safety of the oral Bruton’s tyrosine kinase inhibitor, remibrutinib, in patients with moderate to severe hidradenitis suppurativa in a randomized, phase 2, double-blind, placebo-controlled platform study. Presented as a late-breaking abstract at the American Academy of Dermatology Annual Meeting; March 8-12, 2024; San Diego, California. ClinicalTrials.gov. NCT05147220. Efficacy and safety of remibrutinib compared to teriflunomide in participants with relapsing multiple sclerosis. Available from: https://clinicaltrials.gov/study/NCT05147220 [Last accessed: May 2024]. ClinicalTrials.gov. NCT05156281. Efficacy and safety of remibrutinib compared to teriflunomide in participants with relapsing multiple sclerosis (RMS) (REMODEL-2). Available from: https://clinicaltrials.gov/study/NCT05156281 [Last accessed: May 2024]. ClinicalTrials.gov. NCT03827798. Study of efficacy and safety of investigational treatments in patients with moderate to severe hidradenitis suppurativa. Available from: https://clinicaltrials.gov/ct2/show/NCT03827798. [Last accessed: May 2024]. ClinicalTrials.gov. NCT05432388. Study of efficacy, safety and tolerability of remibrutinib in adult participants with an allergy to peanuts. Available from: https://clinicaltrials.gov/study/NCT05432388 [Last accessed: May 2024]. ClinicalTrials.gov. NCT05976243. Study to investigate efficacy, safety, and tolerability of remibrutinib compared with placebo in adults with CINDU inadequately controlled by H1-antihistamines. Available from: https://clinicaltrials.gov/study/NCT05976243. [Last accessed: May 2024]. Maurer M, Berger W, Giménez-Arnau A, et al. Remibrutinib, a novel BTK inhibitor, demonstrates promising efficacy and safety in chronic spontaneous urticaria. J Allergy Clin Immunol 2022; 150: 1498-1506. Angst D, Gessier F, Janser P, et al. Discovery of LOU064 (remibrutinib), a potent and highly selective covalent inhibitor of Bruton's Tyrosine Kinase. J Med Chem 2020; 63: 5102-5118. Powell RJ, Leech SC, Till S, et al. BSACI guideline for the management of chronic urticaria and angioedema. Clin Exp Allergy 2015; 45: 547-565. Jain V, Giménez-Arnau A, Hayama K, et al. Remibrutinib demonstrates favorable safety profile and sustained efficacy in chronic spontaneous urticaria over 52 weeks. J Allergy Clin Immunol 2024; 153: 479-486. Patient. Antihistamines. Last updated 12 October 2022. Available from: https://patient.info/allergies-blood-immune/allergies/antihistamines [Last accessed: May 2024]. Novartis. Data on file. Genentech USA, Inc. and Novartis Pharmaceuticals Corporation. Xolair Omalizumab. Chronic Spontaneous Urticaria (CSU). Available from: https://www.xolair.com/chronic-spontaneous-urticaria.html [Last accessed: May 2024]. ClinicalTrials.gov. NCT05030311. A Phase 3 study of efficacy and safety of remibrutinib in the treatment of CSU in adults inadequately controlled by H1 antihistamines (REMIX-1). Available from: https://clinicaltrials.gov/study/NCT05030311 [Last accessed: May 2024]. ClinicalTrials.gov. NCT05032157. A Phase 3 study of efficacy and safety of remibrutinib in the treatment of CSU in adults inadequately controlled by H1- antihistamines (REMIX-2). Available from: https://clinicaltrials.gov/study/NCT05032157 [Last accessed: May 2024]. Zuberbier T, Abdul Latiff AH, Abuzakouk M, et al. The international EAACI/GA²LEN/EuroGuiDerm/APAAACI guideline for the definition, classification, diagnosis, and management of urticaria. Allergy 2022; 77: 734-766. The content above comes from the network. if any infringement, please contact us to modify.

临床结果临床3期

100 项与 Remibrutinib 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
复发性多发性硬化	临床3期	美国	Novartis Pharmaceuticals Corp.	2021-12-13
复发性多发性硬化	临床3期	美国	诺华（中国）生物医学研究有限公司	2021-12-13
复发性多发性硬化	临床3期	中国	Novartis Pharmaceuticals Corp.	2021-12-13
复发性多发性硬化	临床3期	日本	Novartis Pharmaceuticals Corp.	2021-12-13
复发性多发性硬化	临床3期	日本	诺华（中国）生物医学研究有限公司	2021-12-13
复发性多发性硬化	临床3期	阿根廷	Novartis Pharmaceuticals Corp.	2021-12-13
复发性多发性硬化	临床3期	阿根廷	诺华（中国）生物医学研究有限公司	2021-12-13
复发性多发性硬化	临床3期	巴西	诺华（中国）生物医学研究有限公司	2021-12-13
复发性多发性硬化	临床3期	巴西	Novartis Pharmaceuticals Corp.	2021-12-13
复发性多发性硬化	临床3期	保加利亚	诺华（中国）生物医学研究有限公司	2021-12-13

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临床结果

适应症

分期

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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


NCT05032157 (REMIX-2, GlobeNewswire) 人工标引	临床3期	慢性荨麻疹	455	Remibrutinib	選醖鑰築簾襯製簾顧糧(艱齋齋醖遞鹽膚蓋鑰艱) = Almost half of patients were completely free of itch and hives (UAS7=0) as assessed at Week 52 壓廠獵糧鏇繭齋艱糧膚 (艱鏇淵艱顧網窪憲醖顧 ) 更多	积极	2024-05-30
				Placebo
NCT05030311 (REMIX-1, GlobeNewswire) 人工标引	临床3期	慢性荨麻疹	470	Remibrutinib	願鹹窪齋選艱糧齋獵選(衊廠範壓選構鏇繭繭願) = Almost half of patients were completely free of itch and hives (UAS7=0) as assessed at Week 52 憲夢壓鑰鑰選繭選壓淵 (鏇廠顧積選鹽鏇襯憲夢 ) 更多	积极	2024-05-30
				Placebo
NEWS 人工标引	临床2期	化脓性汗腺炎	66	Remibrutinib 25 mg	鏇顧壓夢糧製鏇範選鹹(積膚構鹽糧膚鬱觸簾壓) = 鏇積製壓願積壓蓋獵鹹淵鏇蓋觸餘鑰構壓鬱願 (構鑰衊鑰糧鏇製蓋艱鏇 ) 更多	积极	2024-03-09
				Remibrutinib 100 mg	鏇顧壓夢糧製鏇範選鹹(積膚構鹽糧膚鬱觸簾壓) = 築遞選範網網構壓積膚淵鏇蓋觸餘鑰構壓鬱願 (構鑰衊鑰糧鏇製蓋艱鏇 ) 更多
NEWS 人工标引	临床2期	化脓性汗腺炎	77	Remibrutinib 100 mg	鹹願鑰築選選製鹽醖艱(觸鏇餘憲鹽鏇鹽鹹簾獵) = 憲鏇願廠膚鹽窪憲壓願醖壓築廠鏇餘網鹽網鏇 (糧顧鬱齋夢蓋糧鏇衊構 ) 更多	积极	2024-03-09
				Remibrutinib 25 mg	鹹願鑰築選選製鹽醖艱(觸鏇餘憲鹽鏇鹽鹹簾獵) = 遞艱積膚鑰廠廠艱構構醖壓築廠鏇餘網鹽網鏇 (糧顧鬱齋夢蓋糧鏇衊構 ) 更多
NCT05032157 \| NCT05030311 (REMIX-1, GlobeNewswire) 人工标引	临床3期	慢性荨麻疹	462	remibrutinib (REMIX-1)	醖醖範夢願糧齋願膚衊(夢鹹蓋夢遞膚艱壓餘範) = 鹽鹹繭夢襯繭艱鹽願壓膚淵積鏇鑰艱艱廠憲艱 (鹽築糧網襯醖壓築鹹餘, 0.7) 达到更多	积极	2023-11-09
				Placebo (REMIX-1)	醖醖範夢願糧齋願膚衊(夢鹹蓋夢遞膚艱壓餘範) = 鹽選壓製艱範衊壓築築膚淵積鏇鑰艱艱廠憲艱 (鹽築糧網襯醖壓築鹹餘, 1.0) 达到更多
NCT03926611 (Phase 2b study, EADV2023)	临床2期	慢性荨麻疹	309	Remibrutinib 10 mg once daily	齋鬱鬱選顧繭獵壓淵醖(醖糧範醖衊觸選襯糧觸) = 襯壓淵壓範壓築鏇鹹廠鏇鹽選積膚壓壓憲範淵 (範襯夢選繭顧窪範選艱 ) 更多	-	2023-10-11
				Remibrutinib 35 mg once daily	齋鬱鬱選顧繭獵壓淵醖(醖糧範醖衊觸選襯糧觸) = 觸衊膚觸窪鑰網膚醖憲鏇鹽選積膚壓壓憲範淵 (範襯夢選繭顧窪範選艱 ) 更多
NCT03926611 (Phase 2b study, EADV2023)	临床2期	慢性荨麻疹	311	Remibrutinib 10 mg once daily	壓構積醖餘蓋製鹽鹽顧(憲築餘選鏇膚艱顧繭觸) = 觸顧繭構齋淵遞遞獵醖遞餘顧構遞襯齋鹹蓋觸 (廠繭鏇艱築簾範鏇淵鏇 )	积极	2023-10-11
				Remibrutinib 35 mg once daily	壓構積醖餘蓋製鹽鹽顧(憲築餘選鏇膚艱顧繭觸) = 壓積齋築鏇膚齋積鹽憲遞餘顧構遞襯齋鹹蓋觸 (廠繭鏇艱築簾範鏇淵鏇 )
NCT05032157 \| NCT05030311 (REMIX-2, Corporate Publications) 人工标引	临床3期	慢性荨麻疹	925	remibrutinib	淵獵窪襯鬱構積衊鹹醖(繭鑰鹽鑰壓窪築範鹹遞) = Both Phase III studies met their primary endpoint of absolute change from baseline in weekly urticaria activity score (UAS7) at Week 12, demonstrating clinically meaningful and statistically significant improvements in disease activity. The studies will continue until Week 52. Remibrutinib also demonstrated a rapid onset of action as illustrated by the improvement of UAS7 at Week 2 in the REMIX-1 and REMIX-2 studies. 鏇範艱構糧鏇鑰觸鏇醖 (簾淵膚膚鑰顧壓範觸夢 ) 达到	积极	2023-08-09
				placebo
NCT04035668 (CTgov)	临床2期	干燥综合征	73	Remibrutinib+placebo (Remibrutinib 100 mg qd)	觸觸鹹壓遞鹽願糧餘醖(窪夢襯顧蓋憲醖鑰願壓) = 繭襯鬱鑰網鹽構艱觸艱夢醖選積觸範顧範獵窪 (鑰觸觸餘製蓋網選齋遞, 鑰鹹獵鹹醖艱鑰鑰鑰顧 ~ 窪製選鹹艱遞鑰簾範糧) 更多	-	2022-12-20
				Remibrutinib (Remibrutinib 100 mg Bid)	觸觸鹹壓遞鹽願糧餘醖(窪夢襯顧蓋憲醖鑰願壓) = 鹹蓋窪鑰網觸構製網淵夢醖選積觸範顧範獵窪 (鑰觸觸餘製蓋網選齋遞, 壓顧蓋蓋製築鹽糧襯構 ~ 廠鏇蓋簾顧鹽膚艱齋願) 更多
NCT03926611 (Pubmed) 人工标引	临床2期	慢性荨麻疹	311	Remibrutinib 10 mg once daily	艱願壓艱齋壓範衊鏇觸(醖夢顧襯鹹壓蓋淵鑰鬱) = 鬱蓋網膚壓製觸製壓窪鹹顧襯壓鏇積艱淵繭顧 (壓觸膚遞廠餘製鹽糧鏇 )	积极	2022-09-09
				Remibrutinib 35 mg once daily	艱願壓艱齋壓範衊鏇觸(醖夢顧襯鹹壓蓋淵鑰鬱) = 襯積艱獵顧積憲淵艱鏇鹹顧襯壓鏇積艱淵繭顧 (壓觸膚遞廠餘製鹽糧鏇 )