A Phase III Multicenter Randomized, Double-Blind, Double-Dummy, Parallel-Group Study To Evaluate The Efficacy And Safety Of Fenebrutinib Compared With Teriflunomide In Adult Patients With Relapsing Multiple Sclerosis

开始日期2023-02-28

申办/合作机构

Hoffmann-La Roche, Inc.

100 项与 Fenebrutinib 相关的临床结果

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100 项与 Fenebrutinib 相关的转化医学

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100 项与 Fenebrutinib 相关的专利（医药）

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项与 Fenebrutinib 相关的文献（医药）

2023-12-01·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.

2023-06-08·Journal of medicinal chemistry1区 · 医学

Discovery of Novel Bruton's Tyrosine Kinase PROTACs with Enhanced Selectivity and Cellular Efficacy.

1区 · 医学

Article

作者: Daryaee, Fereidoon ; Tonge, Peter J ; Rodriguez-Santamaria, Jose A ; Wang, Nan ; Lannigan, William G ; Davoodi, Shabnam ; Corrionero, Ana ; Haley, John D ; Alfonso, Patricia ; Li, Yi-Qian

Bruton's tyrosine kinase (BTK) is a target for treating B-cell malignancies and autoimmune diseases, and several BTK inhibitors are already approved for use in humans. Heterobivalent BTK protein degraders are also in development, based on the premise that proteolysis targeting chimeras (PROTACs) may provide additional therapeutic benefits. However, most BTK PROTACs are based on the BTK inhibitor ibrutinib raising concerns about their selectivity profiles, given the known off-target effects of ibrutinib. Here, we disclose the discovery and in vitro characterization of BTK PROTACs based on the selective BTK inhibitor GDC-0853 and the cereblon recruitment ligand pomalidomide. PTD10 is a highly potent BTK degrader (DC₅₀ 0.5 nM) that inhibited cell growth and induced apoptosis at lower concentrations than the two parent molecules, as well as three previously reported BTK PROTACs, and had improved selectivity compared to ibrutinib-based BTK PROTACs.

2023-03-01·Annals of surgery1区 · 医学

Inhibition of Bruton’s Tyrosine Kinase Activity Attenuates Hemorrhagic Shock-Induced Multiple Organ Dysfunction in Rats

1区 · 医学

Article

作者: Coldewey, Sina M ; Ramos, Hanna Pillmann ; Aimaretti, Eleonora ; Patel, Nikita M ; Thiemermann, Christoph ; Sordi, Regina ; Alves, Gustavo Ferreira ; Collino, Massimo ; Oliveira, Filipe R M B

Objective::

The aim of this study was to investigate (a) the potential of the Bruton's tyrosine kinase (BTK) inhibitors acalabrutinib and fenebrutinib to reduce multiple organ dysfunction syndrome (MODS) in acute (short-term and long-term follow-up) hemorrhagic shock (HS) rat models and (b) whether treatment with either acalabrutinib or fenebrutinib attenuates BTK, NF-κB and NLRP3 activation in HS.

Background::

The MODS caused by an excessive systemic inflammatory response following trauma is associated with a high morbidity and mortality. The protein BTK is known to play a role in the activation of the NLRP3 inflammasome, which is a key component of the innate inflammatory response. However, its role in trauma-hemorrhage is unknown.

Methods::

Acute HS rat models were performed to determine the influence of acalabrutinib or fenebrutinib on MODS. The activation of BTK, NF-κB and NLRP3 pathways were analyzed by western blot in the kidney.

Results::

We demonstrated that (a) HS caused organ injury and/or dysfunction and hypotension (post-resuscitation) in rats, while (b) treatment of HS-rats with either acalabrutinib or fenebrutinib attenuated the organ injury and dysfunction in acute HS models and (c) reduced the activation of BTK, NF- kB and NLRP3 pathways in the kidney.

Conclusion::

Our results point to a role of BTK in the pathophysiology of organ injury and dysfunction caused by trauma/hemorrhage and indicate that BTK inhibitors may be repurposed as a potential therapeutic approach for MODS after trauma and/or hemorrhage.

项与 Fenebrutinib 相关的新闻（医药）

2024-04-02

·PRNewswire

Global Leaders in Cancer Research and Biotech Join The Mark Foundation for Cancer Research's Scientific Advisory and Industry Advisory Committees

Professors Sarah-Jane Dawson, Johanna Joyce, and Charles Swanton join The Mark Foundation's Scientific Advisory Committee; veteran biotech leader Wendy Young joins the Industry Advisory Committee NEW YORK, April 2, 2024 /PRNewswire/ -- The Mark Foundation for Cancer Research, a leading nonprofit dedicated to advancing research that transforms the prevention, diagnosis, and treatment of cancer, proudly announces the appointment of new members to its Scientific Advisory and Industry Advisory Committees. Joining The Mark Foundation Scientific Advisory Committee are distinguished cancer research and clinical oncology experts Sarah-Jane Dawson, MBBS, PhD, of Peter MacCallum Cancer Centre and Centre for Cancer Research University of Melbourne, Australia; Johanna Joyce, PhD, of the University of Lausanne, Switzerland and Ludwig Institute for Cancer Research; and Charles Swanton, MBPhD, of the Francis Crick Institute and University College London. All three are highly accomplished investigators in their respective fields of study and are past recipients of prestigious Mark Foundation ASPIRE awards that supported innovative cancer research projects in their labs. Chaired by Ross Levine, MD, of Memorial Sloan Kettering Cancer Center, the Scientific Advisory Committee is comprised of a stellar group of internationally renowned cancer research experts including Scott Armstrong, MD, PhD, of Dana-Farber Cancer Institute; Catherine Bollard, MBChB, MD, of Children's National Hospital; Elaine Mardis, PhD, of Nationwide Children's Hospital, Daniel Nomura, PhD, of University of California, Berkeley, and E. John Wherry, PhD, of University of Pennsylvania. The committee assists the foundation in reviewing its scientific goals and grant applications, as well as providing strategic advice and support for its research programs and investments. "As the foundation accelerates discovery and development of new cancer therapeutics and diagnostics by funding trailblazing science globally, it is critical to engage with the world's leading experts," said Ross Levine, MD. "The outstanding researchers on our advisory committees provide invaluable guidance and insight to help steer its programs toward success and impact." "The Mark Foundation's funding of high-risk, high-impact research is essential in the quest to achieve real breakthroughs in cancer research," said Johanna Joyce, PhD. "I am honored to join the Scientific Advisory Committee, to support the next generations of scientists and projects that will revolutionize treatments for patients." Joining The Mark Foundation Industry Advisory Committee is Wendy Young, PhD, an experienced biopharma and life science executive with a strong track record of drug discovery success. The Industry Advisory Committee, including active members Hans Bitter, PhD; Pamela Carroll, PhD; Dan Hicklin, PhD; and Markus Renschler, MD, brings together highly accomplished biotechnology and pharmaceutical R&D leaders to help advise the foundation's unique approach to funding drug discovery research and to investing in early-stage oncology companies developing cutting edge therapeutics and diagnostics. "We are thrilled and honored to welcome all of these distinguished scientists to our advisory committees," said Ryan Schoenfeld, PhD, CEO of The Mark Foundation . "Their extensive experience will greatly benefit our commitment to funding high-impact cancer research and bringing discoveries to patients." New Advisory Committee Member brief biographies: Sarah-Jane Dawson, MBBS, FRACP, PhD is a professor and clinician-scientist at the Peter MacCallum Cancer Centre and Centre for Cancer Research at the University of Melbourne. She is the co-program head of the Cancer Biology and Therapeutics Program and Group Leader of the Molecular Biomarkers and Translational Genomics Laboratory. Professor Dawson is also a fellow of the Australian Academy of Health and Medical Sciences. Her research program centers on developing noninvasive blood-based biomarkers ("liquid biopsies") for clinical application, including early detection, risk stratification and disease monitoring in cancer management to improve patient outcomes. Johanna Joyce, PhD, FAACR is a Full Professor at the University of Lausanne, Switzerland, and Full Member of the international Ludwig Institute for Cancer Research. She previously served as the inaugural Executive Director of the multi-institutional Agora Cancer Centre for translational research in Lausanne until 2021. Prior to relocating her lab to Switzerland in 2016, she was a Full Member at Memorial Sloan Kettering Cancer Center and a Full Professor at Weill Cornell Medical School in New York. Professor Joyce's research investigates the microenvironment in which a tumor arises and the critical influence that non-cancerous immune and stromal cells can have on tumor progression, metastasis, and therapeutic response. Charles Swanton, MBPhD, FRCP, FMedSci, FAACR, FRS is Deputy Clinical Director at the Francis Crick Institute and Senior Principal Investigator of the Cancer Evolution and Genome Instability Laboratory. He is also the Royal Society Napier Professor in Cancer and a thoracic oncologist at University College London Hospitals, Chief Clinician of Cancer Research UK, and Chief Investigator of the TRACERx clinical study to decipher lung cancer evolution. Professor Swanton's research focuses on the branched evolutionary histories of solid tumors, processes that drive cancer cell-to-cell variation in the form of new cancer mutations or chromosomal instabilities, and the impact of such cancer diversity on effective immune surveillance and clinical outcome. Wendy Young, PhD is a biotech executive with more than 30 years of experience in the discovery and development of new medicines for patients. She currently serves as a Board Member and Scientific Advisor at several biotech companies and is an Advisor at Google Ventures. Previously, Wendy was the Senior Vice President, Small Molecule Drug Discovery, at Genentech where she actively built and led the research & discovery organization. Under her leadership, more than 25 clinical candidates progressed into development. Additionally, Wendy led the BTK discovery program and is co-inventor of fenebrutinib, which is currently in Phase 3 trials for multiple sclerosis. Prior to joining Genentech, Wendy held leadership roles at Celera Genomics and Scios, a J&J company. Follow these links for more on the entire Mark Foundation Scientific Advisory Committee and Industry Advisory Committee. About The Mark Foundation for Cancer Research The Mark Foundation for Cancer Research, a charitable organization based in New York City, actively partners with scientists worldwide to accelerate research that will transform cancer prevention, diagnosis, and treatment. Since 2017, The Mark Foundation has awarded over $220 million in grants to investigators at more than 100 academic institutions across 16 countries, with research programs focusing on early career support, team science collaboration, new technology innovation, and therapeutics discovery. Additionally, The Mark Foundation maintains a growing portfolio of investments in early-stage cancer diagnostics and therapeutics companies, including several that have transitioned from grantee projects into commercial development. To learn more, please visit . Contact: Linda Heaney [email protected] SOURCE The Mark Foundation for Cancer Research

高管变更临床3期

2024-03-20

·精准药物

氧杂环丁烷在药物发现中的应用

1背景当前药物化学项目集中于更多更具挑战性的生物靶点，候选药物的分子复杂性大大增加。为此，药物研究者们不断寻找创新的功能分子基团以应对这一挑战。今天我们要分享的是伦敦帝国理工学院化学系分子科学研究中心发表在Journal of Medicinal Chemistry上的文章：Oxetanes in Drug Discovery Campaigns。文章介绍了氧杂环丁烷在药物发现中的应用以及应用中的一些优缺点。四元杂环因其具有低分子量，高极性和特异的三维属性而深受研究者们的欢迎，其中氧杂环丁烷基团被报道的更多（图1）。图1. (a) 具有生物活性的四元杂环的例子；（b）文献中报道四元杂环的数量变化氧杂环丁烷基团在天然产物中常有出现，最著名的有FDA批准的紫杉醇（图2a），虽然氧杂环丁烷被证明不是紫杉醇生物活性的必要结构，但含氧杂环丁烷基团的类似物的亲和力和细胞毒性低于紫杉醇的母体结构。图2. (a) 紫杉醇；(b) gem-二甲基和羰基衍生物的等排体 3,3-二取代的氧杂环丁烷可以作为gem-二甲基和羰基的等排体（图2b），Carreira 团队和罗氏公司合作证明氧杂环丁烷可以作为gem-二甲基的等排体来阻断候选药物中C-H活性位点的代谢 [1]；氧杂环丁烷还可以作为羰基的等排体用来改善药物分子的代谢稳定性及提高药物分子的水溶性等性质。2应用举例氧杂环丁烷在专利和学术期刊中广泛出现，目前有七种包含氧杂环丁烷的候选药物正在进行临床试验（图3a-3g）。七种候选药物中有超过50%的结构是氨基-氧杂环丁烷，其中氧杂环丁烷基团可以减弱氨基的碱度。此外，七种化合物中有6种化合物的氧杂环丁烷是3位取代，因为3位取代的稳定性和可合成性更高。通常在药物设计的后期引入氧杂环丁烷来改善先导化合物的PK性质（logD、溶解度、清除率或碱度等）。图3a. Crenolanib[2] 图3b. Fenebrutinib[3]图3b Fenebrutinib中氧杂环丁烷的引入降低了化合物4的pKaH，对化合物的溶解度和药代动力学特性也有一定的益处。图3c. Ziresovir[4]图3c 中Ziresovir，在研发后期通过引入氧杂环丁烷来降低化合物5中氨基的碱度，氧杂环丁烷小体积的特性也有助于降低分布体积，避免药物在组织中堆积，降低了毒性风险。图3d. Lanraplenib[5]图3d 中Entospletinib 由于其不充分的溶解度，与质子泵抑制剂不良的相互作用以及吗啉环氧化导致的高代谢清除率退出了临床开发。在后期优化阶段引入4-乙基哌嗪替换吗啉改善了化合物的代谢稳定性，随后引入氧杂环丁烷替代乙基，降低了化合物的碱度，提高了在 pH 2 和 Caco-2 渗透性下的溶解度。图3e. Danuglipron[6]图3e Danuglipron 中氧杂环丁烷作为一个小的极性头被引入，它增加了化合物的活性，没有对 LogD 和其他物理化学性质（如清除率和毒性）产生负面影响。图3f. GDC-0349[7]图3f 化合物7有较差的游离血浆清除率和避免由细胞色素P450酶类（CYP酶）时间依赖性抑制（TDl），这可能导致药物存在潜在的毒性问题。将嘧啶环换成烷基确实将CYP抑制降低了10倍以上，但心脏毒性增高（hERG：IC50= 8.5 μM），这与叔烷基胺碱度增加有关（pKaH= 7.6）。GDC-0349 在氮上引入氧杂环丁烷取代基降低了pKaH，同时降低了hERG毒性，与化合物7相比，游离血浆清除率也降低了10倍。图3g. PF-06821497[8]图3g中先导化合物8是一种有效的EZH2抑制剂，但代谢稳定性差且溶解度不足。可通过降低LogD和增加立体性来改善这两种特性。最后化合物9引入了甲氧基和氧杂环丁烷，显著改善了代谢和溶解度特性，并使化合物更适合蛋白口袋。图4. 化合物PF-06821497与EZH2的共晶体结构新引入的氧杂环丁烷立体中心对结合很重要，化合物PF-06821497与 EZH2 复合物的共晶结构表明（图4），氧杂环丁烷取代基在蛋白空腔中占据了一个确定的空间，氧杂环丁烷中的CH 基团和两个酪氨酸侧链之间存在两个潜在的 CH−π相互作用。3小结氧杂环丁烷基团在药物发现中有非常重要的应用，研究表明，氧杂环丁烷的稳定性与其取代模式密切相关，其中3,3-二取代最稳定。研究者们揭示了氧杂环丁烷在药物研发中的许多潜在优势，但也发现了很多的挑战。氧杂环丁烷的潜在优势1.氧杂环丁烷的诱导吸电子效应可以降低相邻基团的pKaH （α位降低约2.7、β位降低约1.9、γ位降低约0.7、δ位降低约0.3），可通过引入氧杂环丁烷来减少或消除药物化合物的碱性。2.氧杂环丁烷中sp3杂化的碳原子增加了化合物的立体性，这种构象效应可以增加化合物的水溶性。3.氧杂环丁烷的体积小，极性大，可用于阻断代谢不稳定的位点，并且不会显著增加化合物的分子量和亲脂性。4.氧杂环丁烷可以作为羰基官能团的生物等排体，这可能有助于规避羰基特异性酶降解，提高水溶性，获得新的IP空间。5.氧杂环丁烷适度的环应变可以引导通过活性药物成分（APIs）代谢而被微粒体环氧化物水解酶（mEH）降解，从而避免由CYP酶清除导致的肝毒性。氧杂环丁烷的潜在劣势，面临的挑战及未来的方向1.氧杂环丁烷的合成仍然具有挑战性。2.氧杂环丁烷构建模块的选择是有限的，这种约束影响了药物化合物中氧杂环丁烷结构的取代模式。3.氧杂环丁烷在酸性条件或高温条件下是不稳定的，所以预测给定的氧杂环丁烷取代模式的稳定性是具有挑战性的。4.氧杂环丁烷在严苛条件下的潜在不稳定性可能成为多步大规模合成的问题，所以通常氧杂环丁烷仅在药物开发的最后阶段引入，以补救一些有问题的物理化学性质，如溶解度或代谢稳定性。5.氧杂环丁烷化合物相关性质的数据集有限，限制了基于数据的预测。参考文献（上下滑动可查看更多）本文：Rojas, J. Oxetanes in Drug Discovery Campaigns. J. Med. Chem. 2023, 66, 12697–12709.[1]. Wuitschik, G.; etal. Oxetanes as Promising Modules in Drug Discovery. Angew. Chem., Int. Ed. 2006, 45, 7736−7739.[2]. Smith, C. C.; etal. Crenolanib Is a Selective Type I Pan-FLT3 Inhibitor. Proc. Natl. Acad. Sci. U. S. A. 2014, 111, 5319−5324.[3]. Crawford, J. J.; Zhang, H. In ACS Symposium Series; American Chemical Society, 2019; Vol. 1332, pp 239−266.[4]. Zheng, X.; etal. Discovery of Benzoazepinequinoline (BAQ) Derivatives as Novel, Potent, Orally Bioavailable Respiratory Syncytial Virus Fusion Inhibitors. J. Med. Chem. 2018, 61, 10228−10241.[5]. Blomgren, P.; etal. Discovery of Lanraplenib (GS-9876): A Once-Daily Spleen Tyrosine Kinase Inhibitor for Autoimmune Diseases. ACS Med. Chem. Lett. 2020, 11, 506−513.[6]. Griffith, D. A.; etal. A Small-Molecule Oral Agonist of the Human Glucagon-like Peptide-1 Receptor. J. Med. Chem. 2022, 65, 8208−8226.[7]. Pei, Z.; etal. Discovery and Biological Profiling of Potent and Selective mTOR Inhibitor GDC-0349. ACS Med. Chem. Lett. 2013, 4, 103−107.[8]. Kung, P.-P.; etal. Optimization of Orally Bioavailable Enhancer of Zeste Homolog 2 (EZH2) Inhibitors Using Ligand and Property-Based Design Strategies: Identification of Development Candidate (R)-5,8-Dichloro-7-(Methoxy(Oxetan-3-yl)Methyl)-2-((4- Methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3,4-dihy-droisoquinolin-1(2H)-one (PF-06821497). J. Med. Chem. 2018, 61, 650−665.声明：发表/转载本文仅仅是出于传播信息的需要，并不意味着代表本公众号观点或证实其内容的真实性。据此内容作出的任何判断，后果自负。若有侵权，告知必删！长按关注本公众号粉丝群/投稿/授权/广告等请联系公众号助手觉得本文好看，请点这里↓

免疫疗法

2024-03-11

·BioSpace

FDA Rejects Viatris, Mapi’s Long-Acting Multiple Sclerosis Injection

Pictured: A nerve cell attacked by the immune system/iStock, peterschreiber.media The FDA has rejected Viatris and Mapi Pharma’s investigational formulation of glatiramer acetate, dubbed GA Depot 40, for the treatment of relapsing forms of multiple sclerosis, the companies announced on Monday. Details of the FDA’s rejection were scant and the partners only said that they are currently reviewing the Complete Response Letter to better determine the “appropriate next steps” for GA Depot 40. “The companies continue to believe in the potential of the product to provide an important new treatment advancement for patients with multiple sclerosis,” according to the announcement. Glatiramer acetate, the active ingredient of GA Depot 40 is an immunomodulator that targets the inflammatory pathways underpinning multiple sclerosis (MS). The drug itself cannot cross the blood-brain barrier but exerts its effects through peripheral helper cells, which can then potentially enter the brain and reduce inflammation within the central nervous system. Originally developed by Teva Pharmaceuticals, glatiramer acetate was first approved in the U.S. in 1996 for the treatment of relapsing forms of MS. It carries the brand name Copaxone. Viatris and Israel-based partner Mapi were proposing their investigational long-acting formulation of glatiramer acetate, which is designed to be given via an intramuscular injection every four weeks. The partners supported their New Drug Application, which the FDA accepted in August 2023, with Phase III data obtained from more than 1,000 patients who received a total of 13 doses of either 40-mg GA Depot or placebo. Results showed that the long-acting formulation could cut the annualized relapse rate by 30.1% versus placebo, an effect that was statistically significant with a p-value of 0.0066. GA Depot also offered patients a preferable dosing schedule and elicited fewer injection site reactions as compared with other products. At the time, Viatris President Rajiv Malik said in a statement that GA depot, if approved, could “improve patient experience through fewer injections, greater tolerability and increased compliance.” Monday’s rejection continues biopharma’s losing streak in the MS space. Last week, Merck KGaA announced that it was abandoning the development of its BTK inhibitor evobrutinib in MS. The decision comes after the candidate failed two Phase III trials in December 2023, unable to significantly reduce annualized relapse rate versus teriflunomide. Other BTK inhibitors have also stumbled in MS. Sanofi’s tolebrutinib was put under partial clinical hold in June 2022 due to drug-induced liver injury. Roche’s candidate fenebrutinib ran into the same problem in December 2023, when the FDA also put a regulatory pause on the BTK inhibitor for potential liver injury. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

临床3期上市批准临床结果

100 项与 Fenebrutinib 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11457	-	-	DB14785

研发状态

适应症	最高研发状态	国家/地区	公司
多发性硬化症	临床3期	中国台湾更多	罗氏（中国）投资有限公司更多
原发性进行性多发性硬化	临床3期	意大利更多	Hoffmann-La Roche, Inc. 更多
复发性多发性硬化	临床3期	格鲁吉亚更多	Hoffmann-La Roche, Inc. 更多
类风湿关节炎	终止	日本更多	Chugai Pharmaceutical Co., Ltd. 更多
系统性红斑狼疮	终止	巴西更多	Genentech, Inc. 更多

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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


FENhance (Biospace) 人工标引	临床3期	复发性多发性硬化	-	fenebrutinib	窪夢獵網獵積襯築衊夢(衊簾顧繭簾淵願鹹齋顧) = 顧簾製觸築襯鬱築簾壓築鏇襯襯積窪築顧窪鏇 (鹽餘鑰鹽廠窪觸膚蓋構 )	不佳	2023-12-05
NCT05119569 (FENopta, ECTRIMS2023) 人工标引	临床2期	多发性硬化症	106	Fenebrutinib 200 mg	醖製鹹積範願壓簾淵積(製遞網構鑰憲餘蓋遞醖) = 憲憲鏇齋膚齋鏇願獵鬱齋選糧鹽繭憲襯鑰獵壓 (糧襯窪選鹹簾淵糧簾壓 ) 更多	积极	2023-10-17
				Placebo	醖製鹹積範願壓簾淵積(製遞網構鑰憲餘蓋遞醖) = 繭餘顧艱鏇夢蓋獵觸鹽齋選糧鹽繭憲襯鑰獵壓 (糧襯窪選鹹簾淵糧簾壓 ) 更多
NCT03407482 (CTgov)	临床2期	系统性红斑狼疮	160	GDC-0853	鑰壓艱鹽壓構觸獵襯憲(製願繭淵製鑰鏇簾蓋窪) = 壓鹹鹽艱觸積鑰膚憲構廠餘鏇製鏇艱廠蓋夢範 (積獵餘鹹鏇襯鑰積範簾, 醖憲遞襯齋廠壓鏇鏇淵 ~ 膚蓋淵膚遞鑰鹽簾鏇構) 更多	-	2020-12-19
NCT03137069 (CTgov)	临床2期	慢性荨麻疹	134	Placebo (Cohort 1: Placebo)	簾選簾築艱衊廠鑰觸網(繭鑰醖繭鹹觸範簾衊夢) = 遞顧網淵選選鬱製顧廠顧構鹽齋襯鏇範觸齋淵 (繭艱淵繭窪顧蓋繭鏇鹽, 憲構鏇廠顧壓齋艱鏇選 ~ 糧願衊蓋構簾襯憲鑰獵) 更多	-	2020-09-29
				GDC-0853 (Cohort 1: GDC-0853 200mg BID)	簾選簾築艱衊廠鑰觸網(繭鑰醖繭鹹觸範簾衊夢) = 構鏇醖餘築糧網鑰範選顧構鹽齋襯鏇範觸齋淵 (繭艱淵繭窪顧蓋繭鏇鹽, 膚窪艱網壓襯衊鑰構鹽 ~ 糧淵願獵醖繭憲餘鹹遞) 更多
NCT03693625 (CTgov)	临床2期	慢性荨麻疹	31	GDC-0853 (Parent Study: GDC-0853)	繭願膚遞糧繭願願餘積(選憲餘鬱艱衊選鹽鬱選) = 蓋膚製餘襯膚廠鬱範網顧襯願網獵繭餘憲艱獵 (鹹築鏇築願範獵鬱夢積, 醖齋網觸選積積衊製鏇 ~ 範獵遞齋製願廠醖窪簾) 更多	-	2020-09-25
				GDC-0853 (Parent Study: Placebo)	繭願膚遞糧繭願願餘積(選憲餘鬱艱衊選鹽鬱選) = 築構鏇觸齋築構窪積齋顧襯願網獵繭餘憲艱獵 (鹹築鏇築願範獵鬱夢積, 顧窪壓製範範鏇簾齋製 ~ 構構醖壓築獵窪膚淵構) 更多
NCT02983227 (CTgov)	临床2期	类风湿关节炎	496	GDC-0853 (GDC-0853 (200mg BID) Cohort 1)	構膚鹹蓋壓夢願膚膚鹽(積窪繭觸窪獵窪醖網夢) = 觸襯窪憲鑰築願鑰窪衊衊鏇築膚簾膚醖獵窪壓 (繭鏇糧遞膚積構獵廠夢, 網淵製憲簾衊膚鑰淵願 ~ 糧膚膚餘鏇憲遞艱簾艱) 更多	-	2020-08-03
				GDC-0853 (GDC-0853 (200mg BID) Cohort 2)	構膚鹹蓋壓夢願膚膚鹽(積窪繭觸窪獵窪醖網夢) = 窪遞壓糧淵築觸選築醖衊鏇築膚簾膚醖獵窪壓 (繭鏇糧遞膚積構獵廠夢, 醖蓋範壓衊齋簾膚鬱網 ~ 齋艱簾醖廠夢網蓋憲窪) 更多
NCT02908100 (CTgov)	临床2期	系统性红斑狼疮	260	placebo (Placebo)	壓餘衊繭糧壓簾鏇艱餘(願範鬱廠顧鏇構網鹹膚) = 繭襯遞繭積窪壓糧夢蓋膚壓齋壓憲構鹹齋廠襯 (膚鏇鑰製製膚夢膚憲簾, 蓋構獵積遞襯壓鬱願蓋 ~ 糧廠顧網廠鏇衊艱廠艱) 更多	-	2020-07-07
				GDC-0853 (GDC-0853 (150mg) QD)	壓餘衊繭糧壓簾鏇艱餘(願範鬱廠顧鏇構網鹹膚) = 願齋鬱選廠獵積鑰齋鬱膚壓齋壓憲構鹹齋廠襯 (膚鏇鑰製製膚夢膚憲簾, 蓋憲鹽艱構構網夢繭夢 ~ 醖鹽築網積範鏇醖鬱獵) 更多
NCT02833350 (CTgov)	临床2期	类风湿关节炎	578	Placebo+GDC-0853+Folic Acid+MTX (Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo)	構範鹽蓋鹹願繭積鏇鑰(窪繭糧選齋鹽簾淵鹹壓) = 廠壓鏇鏇襯壓蓋窪構蓋衊選夢膚鏇糧衊鏇繭餘 (製艱膚廠鬱製齋窪範鏇, 餘膚艱繭製鏇襯壓蓋鬱 ~ 蓋鑰構衊窪積鑰衊願膚) 更多	-	2019-09-10
				Placebo+GDC-0853+Folic Acid+MTX (Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo)	構範鹽蓋鹹願繭積鏇鑰(窪繭糧選齋鹽簾淵鹹壓) = 願淵鬱構衊齋鑰網鏇窪衊選夢膚鏇糧衊鏇繭餘 (製艱膚廠鬱製齋窪範鏇, 繭鹽鬱淵鹹醖齋膚艱觸 ~ 餘範鏇鏇壓齋襯廠構遞) 更多
EULAR2019	临床2期	-	-	Fenebrutinib 50 mg QD	觸艱遞構艱鬱鹽衊網衊(膚窪顧廠積餘鏇蓋夢膚) = 獵構衊積鹽製鹽膚糧艱鹽鬱構鹽餘醖鬱鹹遞廠 (淵選襯蓋衊壓觸餘廠壓, (6% ~ 29%))	-	2019-06-12
				Fenebrutinib 150 mg QD	觸艱遞構艱鬱鹽衊網衊(膚窪顧廠積餘鏇蓋夢膚) = 夢構膚壓壓鹹蓋夢築衊鹽鬱構鹽餘醖鬱鹹遞廠 (淵選襯蓋衊壓觸餘廠壓, (19% ~ 36%))
EULAR2019	N/A	类风湿关节炎 rheumatoid factor \| total IgM \| CCL4 ... 更多	-	Fenebrutinib 50 mg qD	憲蓋範鹽衊廠構醖積衊(艱壓糧鬱構顧淵構顧淵) = 鏇鹹壓夢選鹹簾觸獵餘鹹醖襯構遞鏇獵鬱網遞 (鏇築齋醖構淵襯廠製範 ) 更多	积极	2019-06-12
				Fenebrutinib 150 mg qD	憲蓋範鹽衊廠構醖積衊(艱壓糧鬱構顧淵構顧淵) = 鏇蓋獵齋鬱壓壓構齋鹹鹹醖襯構遞鏇獵鬱網遞 (鏇築齋醖構淵襯廠製範 ) 更多