主要目的是在已完成了2 期 M19-130 研究的SLE受试者中评价Elsubrutinib和Upadacitinib单药治疗或作为 ABBV-599（Elsubrutinib/Upadacitinib ）联合治疗的长期安全性和耐受性。次要目的是获得在RCT 研究（单药治疗和联合治疗）治疗超过48 周后的长期疗效数据，以更充分地评估每种治疗随着时间推移的获益风险。

开始日期2021-08-23

申办/合作机构

AbbVie Deutschland GmbH & Co. KG

[+2]

JPRN-jRCT2031210119

/ Not yet recruiting临床2期IIT

[M20-186] A Phase 2, Long-Term Extension (LTE) Study With Elsubrutinib and Upadacitinib Given Alone or in Combination (ABBV-599) in Subjects With Moderately to Severely Active Systemic Lupus Erythematosus Who Have Completed the M19-130 Phase 2 Randomized Controlled Trial (RCT)

开始日期2021-04-27

申办/合作机构-

NCT04451772

/ Completed临床2期

A Phase 2, Long-Term Extension (LTE) Study With Elsubrutinib and Upadacitinib Given Alone or in Combination (ABBV-599) in Subjects With Moderately to Severely Active Systemic Lupus Erythematosus Who Have Completed the M19-130 Phase 2 Randomized Controlled Trial (RCT)

Systemic Lupus Erythematosus (SLE) is an immune-mediated disease associated with inflammation of multiple organ systems. This study will evaluate how well elsubrutinib and upadacitinib given alone or as the ABBV-599 combination (elsubrutinib/upadacitinib) works within the body, in participants who completed study M19-130. This study will assess the change in disease symptoms.
ABBV-599 is an investigational drug being developed for the treatment of Systemic Lupus Erythematosus (SLE). This study is "double-blinded", which means that neither the trial participants nor the study doctors will know who will be given which study drug. Study doctors put the participants into 1 of 4 groups called treatment arms. Each group receives a different treatment. Adult participants with a diagnosis of SLE will be enrolled. Around 260 participants will be enrolled in the study in approximately 100 sites worldwide.
Participants will receive the following for up to 56 weeks:
Participants will receive oral elsubrutinib capsules and/or oral upadacitinib tablets once daily for up to 56 weeks. Participants who were receiving elsubrutinib and/or upadacitnib in M19-130 will continue to receive the same treatment in this study. Participants who were receiving placebo in M19-130 will be re-randomized to one of the 2 combination treatment arms in this study.
Arm 1: Elsubrutinib Dose A and Upadacitinib Dose A Arm 2: Elsubrutinib Dose A and Upadacitinib Dose B
There may be higher burden for participants in this trial compared to their standard of care. Participants will attend monthly visits during the course of the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.

开始日期2020-07-27

申办/合作机构

AbbVie, Inc.

100 项与 Elsubrutinib 相关的临床结果

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100 项与 Elsubrutinib 相关的转化医学

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100 项与 Elsubrutinib 相关的专利（医药）

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项与 Elsubrutinib 相关的文献（医药）

2024-12-01·INTERNATIONAL IMMUNOPHARMACOLOGY

Bruton’s tyrosine kinase: A promising target for treating systemic lupus erythematosus

Review

作者: Zhou, Yu ; Sun, Lan ; Feng, Yifan ; Ding, Qiaoyi ; Zhang, Tiantai

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disorder involving multiple organs and systems. There is growing evidence that autoreactive B cells occupy a central role in the occurrence and progression of SLE due to their ability to generate pathogenic autoantibodies. Small molecule inhibitors targeting Bruton's tyrosine kinase (BTK), a crucial intracellular kinase regulating B cell development and function, emerge as a new strategy to treat SLE in recent years and are superior to biologic agents depleting B cells in many aspects. Supportive data obtained from lupus-prone mice preliminarily demonstrated the promising therapeutic potential of BTK inhibition. However, these BTK inhibitors, including elsubrutinib, evobrutinib, etc., mostly face with unsatisfactory efficacy and certain safety issues during clinical use, driving the quest for new-generation inhibitors with improved potency and higher selectivity. This paper elaborates the importance of BTK involvement in SLE pathogenesis, reviews the clinical research progress of BTK inhibitors for SLE and discusses limitations and challenges the drugs met in development, in order to contribute to a deeper understanding of disease mechanism and provide a reference for new-generation BTK inhibitor research.

2024-01-03·MOLECULAR CANCER THERAPEUTICS

Bruton's Tyrosine Kinase Inhibitors with Distinct Binding Modes Reveal Differential Functional Impact on B-Cell Receptor Signaling

Article

作者: Lundgaard, Greta ; Tse, Chris ; Yoon, Woo Hyun ; Gururaja, Tarikere ; Pan, Chin ; Liu, Jing ; Li, Wei ; Souers, Andrew J. ; Sano, Renata ; Wang, Longcheng ; Zhai, Yongjiao ; Yang, Muhua ; Lee, Chih-Hung ; DeAnda, Felix ; Apatira, Mutiah

Abstract:

Small molecule inhibitors of Bruton's tyrosine kinase (BTK) have been approved for the treatment of multiple B-cell malignancies and are being evaluated for autoimmune and inflammatory diseases. Various BTK inhibitors (BTKi) have distinct potencies, selectivity profiles, and binding modes within the ATP-binding site. On the basis of the latter feature, BTKis can be classified into those that occupy the back-pocket, H3 pocket, and the hinge region only. Hypothesizing that differing binding modes may have differential impact on the B-cell receptor (BCR) signaling pathway, we evaluated the activities of multiple BTKis in B-cell lymphoma models in vitro and in vivo. We demonstrated that, although all three types of BTKis potently inhibited BTK-Y223 autophosphorylation and phospholipase C gamma 2 (PLCγ2)-Y1217 transphosphorylation, hinge-only binders were defective in inhibiting BTK-mediated calcium mobilization upon BCR activation. In addition, PLCγ2 activation was effectively blocked by back-pocket and H3 pocket binders but not by hinge-only binders. Further investigation using TMD8 cells deficient in Rac family small GTPase 2 (RAC2) revealed that RAC2 functioned as a bypass mechanism, allowing for residual BCR signaling and PLCγ2 activation when BTK kinase activity was fully inhibited by the hinge-only binders. These data reveal a kinase activity–independent function of BTK, involving RAC2 in transducing BCR signaling events, and provide mechanistic rationale for the selection of clinical candidates for B-cell lymphoma indications.

2022-06-01·The Lancet. Rheumatology

Safety and efficacy of elsubrutinib or upadacitinib alone or in combination (ABBV-599) in patients with rheumatoid arthritis and inadequate response or intolerance to biological therapies: a multicentre, double-blind, randomised, controlled, phase 2 trial

Article

作者: Cohen, Stanley ; Cortes-Maisonet, Gregorio ; Drescher, Edit ; Singhal, Atul ; Blanco, Ricardo ; Doan, Thao ; Housley, William ; Taylor, Peter C. ; Nader, Ahmed ; Wang, Zailong ; Fleischmann, Roy ; Lu, Wenjing ; Friedman, Alan

BACKGROUND:

ABBV-599 is a novel fixed-dose combination of the Bruton's tyrosine kinase (BTK) inhibitor elsubrutinib and the Janus kinase (JAK) inhibitor upadacitinib under investigation for the treatment of autoimmune diseases. We aimed to determine whether ABBV-599 could increase the treatment response for patients with active rheumatoid arthritis compared with inhibiting either pathway alone, while maintaining an acceptable safety profile.

METHODS:

We conducted a multicentre, double-blind, parallel-group, dose-exploratory, randomised, controlled, phase 2 trial at 75 community sites in eight countries in Europe and North America. We enrolled patients who were 18 years or older with rheumatoid arthritis and inadequate response or intolerance to biological disease-modifying antirheumatic drugs. Eligible patients were randomly assigned (3:2:2:2:2:1) via interactive response technology to receive daily, orally administered ABBV-599 (ie, upadacitinib 15 mg plus elsubrutinib 60 mg), elsubrutinib 60 mg, elsubrutinib 20 mg, elsubrutinib 5 mg, upadacitinib 15 mg, or placebo. Randomisation was stratified by the number of previous biological disease-modifying antirheumatic drugs. The investigator, study site personnel, and patients were masked throughout the study. The primary endpoint was change from baseline in disease activity score of 28 joints with C-reactive protein (DAS28-CRP) at week 12 for all patients who received a study drug. Pharmacokinetics and safety were also assessed. This study is registered with ClinicalTrials.gov, number NCT03682705.

FINDINGS:

Between Oct 8, 2018, and March 26, 2020, 242 patients were randomly assigned to receive ABBV-599 (n=62), elsubrutinib 60 mg (n=41), elsubrutinib 20 mg (n=39), elsubrutinib 5 mg (n=41), upadacitinib 15 mg (n=40), or placebo (n=19). Of the 242 patients, 204 (84%) were female, 38 (16%) were male, and 220 (91%) were White; the mean age at baseline was 58·0 years (SD 11·3). Compared with placebo, the least squares mean changes from baseline in DAS28-CRP were -1·44 (90% CI -2·03 to -0·85; p<0·0001) for ABBV-599, -0·40 (-1·03 to 0·23; p=0·29) for elsubrutinib 60 mg, -0·20 (-0·85 to 0·44; p=0·61) for elsubrutinib 20 mg, -0·21 (-0·84 to 0·41; p=0·57) for elsubrutinib 5 mg, and -1·75 (-2·38 to -1·13; p<0·0001) for upadacitinib. No significant improvements in efficacy measures for elsubrutinib alone (any dose) versus placebo were detected, despite adequate plasma exposure and target engagement. Treatment-emergent adverse events were observed in 113 (47%) of 242 patients, with similar proportions for all groups.

INTERPRETATION:

Significant improvements in disease activity metrics of rheumatoid arthritis with ABBV-599 were driven by the JAK inhibitor upadacitinib with no discernible effect by the BTK inhibitor elsubrutinib.

FUNDING:

AbbVie.

项与 Elsubrutinib 相关的新闻（医药）

2024-12-12

·药精通Bio

自免疾病: 系统性红斑狼疮 (SLE) 的靶向治疗进展

系统性红斑狼疮（SLE，Systemic lupus erythematosus）通常称为狼疮，是一种累及多系统的系统性自身免疫性疾病，具有显著的发病率和死亡率。系统性红斑狼疮患者经常会经历疾病发作和缓解的交替时期。SLE 的表现多种多样，从皮疹和关节炎到贫血和血小板减少，再到浆膜炎、肾炎、癫痫发作和精神病。据估计，大约 90% 的 SLE 患者是女性，大多数病例年龄在 15 至 44 岁之间。SLE 女性怀孕被认为是高风险，与一般人群相比，孕产妇和新生儿的发病率和死亡率较高。近年来，精细免疫表型、全基因组关联研究（GWAS）、单细胞测序、多组学分析和基因编辑的进展显着增强了对SLE发病机制的理解。这些技术突破还推动了针对免疫细胞、共刺激分子、细胞因子和信号转导途径的疗法的开发和临床研究，包括单克隆抗体、小分子药物和嵌合抗原受体（CAR-）T细胞免疫疗法。贝利木单抗（Belimumab）和阿尼鲁单抗（Anifrolumab）等治疗方法的批准为临床医生、研究人员和患者提供了更大的信心和更多的选择来治疗中度至重度系统性红斑狼疮，特别是难治性病例。１.　FDA 已批准 SLE 靶向治疗Belimumab（Benlysta） Belimumab（Benlysta）由 GSK 开发，是第一个 B 淋巴细胞刺激剂（BlyS）的靶向抑制剂。通过与 BlyS 结合，Belimumab 抑制 B 细胞（包括自身反应性 B 细胞）的存活，并减少其分化为负责产生免疫球蛋白的浆细胞，尽管它不直接与 B 细胞结合。贝利木单抗最初于 2011 年 3 月获得 FDA 批准用于治疗 SLE，是首个 SLE 靶向疗法，贝利木单抗于 2020 年 12 月获得扩大批准用于治疗狼疮性肾炎。它通常与羟氯喹（Plaquenil）和吗替麦考酚酯（CellCept）等其他药物联合使用，以增强治疗效果。Anifrolumab（Saphnelo） Saphnelo（anifrolumab）是一种全人源单克隆抗体，可与 I 型 IFN 受体的亚基 1 结合，有效阻断 I 型 IFN 的活性。I 型 IFN，例如 IFN-α、IFN-β 和 IFN-κ，是参与调节 SLE 相关炎症途径的细胞因子。在大多数成年 SLE 患者中观察到 I 型 IFN 信号传导活性增加，并且与疾病严重程度相关。作为“首创新药”I 型 IFN 受体拮抗剂，Saphnelo 代表了 SLE 治疗的重大进步。2021年8月2日，美国FDA批准Saphnelo用于治疗中重度SLE。２.　治疗 SLE 的靶向疗法正在开发中表 1. 治疗系统性红斑狼疮的靶向疗法聚乙二醇化抗体 - Dapirolizumab Dapirolizumab pegol 是一种新型研究中人源化无 Fc聚乙二醇 (PEG) 缀合的抗原结合 (Fab') 片段。它抑制 CD40L 信号传导，已被证明可以减少 B 细胞活化和自身抗体产生，减轻 IFN-I 分泌，并减弱 T 细胞和抗原呈递细胞 (APC) 活化。 2024 年 9 月 24 日，UCB 和 Biogen 联合宣布 III 期 PHOENYCS GO 研究评估 dapirolizumab pegol 治疗 SLE 的效果积极。 PHOENYCS GO 是一项多中心、随机、双盲、安慰剂对照、平行的 III 期试验，旨在评估dapirolizumab联合标准护理 (SOC) 疗法与安慰剂加 SOC 疗法在患有以下疾病的患者中的疗效和安全性，包括中度至重度系统性红斑狼疮，共有 321 名患者参与了该研究。分析显示，dapirolizumab pegol 与 SOC 相结合，达到了其主要终点。BICLA方法评估中，第 48 周时，与安慰剂加 SOC 相比，患者的中度至重度疾病活动度显著改善。BICLA 是一个既定的复合终点，用于通过患者病史、临床检查和实验室测试评估临床疾病活动性。此外，评估疾病活动和耀斑的关键次要终点显示出具有临床意义的改善。 dapirolizumab pegol 的安全性与之前的研究一致，并且与接受免疫调节治疗的 SLE 患者的预期安全结果一致。Litifilimab（利替非利单抗） Litifilimab (BIIB059) 由 Biogen 开发，是一种靶向 BDCA2 的全人源化 IgG1 mAb。通过抑制 BDCA2，它可以减少炎症细胞因子（包括 IFN-I）的产生，在调节 SLE 的病理机制中发挥着至关重要的作用。Litifilimab　是目前最先进的BDCA2靶向疗法，已进入治疗皮肤红斑狼疮（CLE）和SLE的III期临床试验。图 1. Litifilimab 的作用机制在一项涉及 SLE 参与者的 2 期试验中，在 24 周内，与安慰剂相比，litifilimab 与基线相比，肿胀和压痛关节的数量有更大程度的减少。需要更长时间和更大规模的试验来确定Litifilimab治疗 SLE 的安全性和有效性。JAK 抑制剂 - Upadacitinib Upadacitinib 是一种选择性、可逆性 JAK 抑制剂，正在研究用于治疗各种严重的免疫介导的炎症性疾病。在细胞和酶活性测定中，与 JAK2、JAK3 和 TYK2 相比，upadacitinib 对 JAK1 显示出特异的强的抑制作用。该药物已被批准用于治疗成人中度至重度类风湿性关节炎、银屑病关节炎、溃疡性结肠炎和强直性脊柱炎。 2023 年，艾伯维宣布了 upadacitinib 的 2 期临床试验取得积极结果，该试验可作为单一疗法或联合使用（elsubrutinib 60 mg 和 upadacitinib 30 mg），用于治疗继续接受标准狼疮治疗的中度至重度 SLE 成人的疗法。基于这些结果，艾伯维表示将推进upadacitinib进入SLE治疗的3期临床试验。S1P1 调节剂 - Cenerimod Cenerimod 是一种潜在的“FIC”、高选择性 S1P1 受体调节剂。这种每日一次的口服片剂正在开发用于治疗系统性红斑狼疮。2022 年 12 月，Idorsia 启动了 OPUS 项目，该项目由两项多中心、随机、双盲、安慰剂对照 3 期试验组成，旨在评估 cenerimod 与中重度 SLE 成人患者的疗效、安全性和耐受性。Cenerimod 已获得美国 FDA 授予的治疗 SLE 的快速通道资格。在 II 期临床试验中，测试的最高剂量为 4 mg，六个月后，与安慰剂相比，治疗组在主要终点（mSLEDAI-2K 评分）上显示出数值改善。然而，除了 4 mg 剂量（p＝ 0.029）外，其他组中没有观察到显着差异。此外，在第 52 周时，所有试验组的 mSLEDAI-2K 和 SRI-4 评分均未发现显著差异。细胞治疗 - KYV-101 KYV-101 是一种新型全人源抗 CD19 嵌合抗原受体 (CAR) T 细胞疗法，旨在用于 B 细胞驱动的自身免疫性疾病。它专门靶向 CD19，这是一种在 B 细胞表面表达的蛋白质。B 细胞除了与许多类型的恶性肿瘤有关，也与自身免疫性疾病相关。 References: [1] Dapirolizumab Pegol Phase 3 Data Presented at the American College of Rheumatology Shows Significant Reduction in Systemic Lupus Erythematosus Disease Activity .[2] Trial of Anti-BDCA2 Antibody Litifilimab for Systemic Lupus Erythematosus,10.1056/NEJMoa2118025 [3]Phase 2 Study of Upadacitinib (RINVOQ®) Alone or as a Combination Therapy Meets Primary and Key Secondary Endpoints in Patients with Systemic Lupus Erythematosus [4] Encouraging Phase 2 data on cenerimod – Idorsia's S1P1 receptor modulator currently investigated for SLE – presented at ACR 2019 END 免责声明：本文仅作知识交流与分享及科普目的，不涉及商业宣传，不作为相关医疗指导或用药建议。文章如有侵权请联系删除。 OTC2024类器官前沿应用与3D细胞培养论坛圆满落幕，点击图片可查看会后报告，咨询OTC2025类器官论坛请联系：王晨 180 1628 8769

免疫疗法细胞疗法临床研究临床结果

2024-11-04

·PRNewswire

Lupus Research Alliance Announces Lupus Research Highlights at ACR Convergence 2024

Sixteen presentations of preclinical studies funded by the Lupus Research Alliance (LRA) to advance understanding of lupus and potential treatment pathways, including four oral presentations Two reports by Lupus Therapeutics, the clinical affiliate of the LRA, and the Lupus Clinical Investigators Network (LuCIN) on promoting equity in lupus clinical trials, and identifying trial barriers and solutions Fifteen industry-sponsored clinical research studies supported by Lupus Therapeutics and LuCIN, including positive results from the late-breaking Phase 3 dapirolizumab pegol trial NEW YORK, Nov. 4, 2024 /PRNewswire/ -- The Lupus Research Alliance (LRA), the largest private funder of lupus research worldwide, today announced that a total of 33 studies, funded by the organization or supported by its clinical research affiliate Lupus Therapeutics, will be presented at ACR Convergence 2024. The annual meeting of the American College of Rheumatology takes place November 14-19, at the Walter E. Washington Convention Center in Washington, D.C. The LRA, which seeks to accelerate the discovery and development of patient-centered treatments and diagnostics, pursues strategies to spur advancements from "bench to bedside." LRA-supported studies presented at ACR Convergence 2024 represent the full continuum of lupus research, from foundational research exploring new avenues of knowledge, to clinical trials evaluating potential new treatments. "ACR Convergence 2024 is met with pride and excitement by the Lupus Research Alliance and Lupus Therapeutics – pride in seeing the fruits of our funding and other initiatives to accelerate drug discovery and development, and excitement as we stand on the precipice of some important advancements," said LRA President and CEO Albert T. Roy. "There are more trials in mid-to-late-stage development than ever before, including dapirolizumab pegol in Phase 3 from UCB/Biogen, a Lupus Therapeutics partner. And we are gratified to witness the volume of CAR T cell therapy approaches in clinical development, having invested in 2014 in early research suggesting this approach as a promising intervention to explore for treating lupus," Roy added. Foundational Research Funded by the LRA Sixteen studies of LRA-funded research (four oral presentations and 12 posters) will be presented. Several focus on Childhood-Onset Systemic Lupus Erythematosus (cSLE), including: a detailed characterization of the disease; the effects of fatigue on pediatric patients' mental and physical health; and the discovery of Anti-Mitochondrial Antibodies (AMA), which are linked to higher disease activity. Other studies include: the development of a precision immunotherapy to target harmful B cells in Antiphospholipid Syndrome (APS) patients; the discovery of innate signaling pathways crucial in causing inflammation in lupus patients; and the epidemiology of strokes in children and adults with lupus. ORAL PRESENTATIONS Saturday, Nov. 16 Abstract #0837: Bispecific Autoantigen-T Cell Engagers (BaiTE) to Selectively Target Autoreactive B Cells in Antiphospholipid Syndrome 3:00-3:15 PM, Room 103AB Sunday, Nov. 17 Abstract #1702: Placental Developmental Defects in a Humanized-TLR8 Mouse Model of Spontaneous Anti-Phospholipid Antibody Induced Pregnancy Loss 3:15-3:30 PM , Room 103AB Monday, Nov. 18 Xist and XChromosome Inactivation in Female Biased Autoimmunity 9:00-9:30 AM, Room 145AB Abstract #2625: Brain Injury Markers Correlate with Impaired Executive Function and Disease Activity in Children with Systemic Lupus Erythematosus 3:30-3:45 PM, Room 202AB POSTERS Saturday, Nov. 16 Poster Session A, 10:30 AM-12:30 PM, Poster Hall: Abstract #0091: Targeting Endothelial Dysfunction in Lupus Nephritis: Effect of Sepiapterin, a Drug That Restores Endothelial Nitric Oxide Synthase Function, in a Murine Model of Lupus Nephritis Abstract #0098: Anti-HSP90α as a Protective Natural Antibody Against Secondary Antiphospholipid Syndrome in Systemic Lupus Erythematosus Sunday, Nov. 17 Poster Session B, 10:30 AM-12:30 PM , Poster Hall: Abstract #1266: Anti-Mitochondrial Antibodies Associate with Disease Activity and IFNα Expression in Childhood-onset Systemic Lupus Erythematosus Abstract #1273: An Investigation of Traumatic Events and Mental Health in cSLE Abstract #1274: Comparing Performance-Based Measures and Self-Reported Questionnaires for Assessment of Executive Function for Youth with Childhood-Onset Systemic Lupus Erythematosus Abstract #1278: The Effects of Fatigue on Self-Reported Mental and Physical Health in Childhood-Onset Systemic Lupus Erythematosus: A Cross-Sectional Study Abstract #1279: Cerebrovascular Accidents in Pediatric and Adult Systemic Lupus Erythematosus: A Comparison of Epidemiology and Outcomes Abstract #1280: Abnormal Cortical Gyrification Patterns in Adolescents with Childhood-onset SLE: Early Associations with Perceived Fatigue Abstract #1504: Novel Analytes Associated with Cognitive Impairment in Patients with Systemic Lupus Erythematosus: Serum S100A8/A9, MMP-9 and IL-6 Abstract #1506: Cognitive Impairment Prevalence and Most Affected Domains in Patients with SLE by the ACR Comprehensive Neuropsychological Battery Monday, Nov. 18 Poster Session C, 10:30 AM-12:30 PM, Poster Hall: Abstract #1788: Memory B Cell Activation and Dysregulation in Systemic Lupus Erythematosus Abstract #2380: Characterizing SLE Patients into Type 1 and Type 2 Disease States: Insights from a Single Lupus Cohort Research Conducted by Lupus Therapeutics and the Lupus Clinical Investigators Network (LuCIN) Lupus Therapeutics, the clinical affiliate of the Lupus Research Alliance, oversees the Lupus Clinical Investigators Network (LuCIN), consisting of 50+ premier, leading medical research institutions in North America, comprised of 200+ providers with expertise in lupus care and clinical trials. The following studies are based on annual surveys of LuCIN investigators and research teams on promoting equity in lupus clinical trials and identifying trial barriers and solutions. POSTERS Saturday, Nov. 16 Abstract 0180: Collaborative Solutions to Lupus Trial Challenges for Underrepresented Participant Recruitment & Engagement: Perspectives from the Lupus Clinical Investigators Network (LuCIN) Poster Session A, 10:30 AM-12:30 PM, Poster Hall Sunday, Nov. 17 Abstract #1039: Through the LuCIN Lens: Defining Barriers and Forging Solutions for Lupus Clinical Trials in North America Poster Session B, 10:30 AM-12:30 PM, Poster Hall Clinical Research Supported by Lupus Therapeutics and LuCIN The primary goal of Lupus Therapeutics and LuCIN is to accelerate and enhance the quality of lupus clinical trials through clinical expertise, advisory services, patient engagement and partnership/collaboration with biopharmaceutical companies and research partners. Lupus Therapeutics and LuCIN are involved in nearly 25% of active lupus clinical trials. Fifteen Lupus Therapeutics/LuCIN-supported programs and collaborations are being presented at ACR Convergence 2024: ORAL PRESENTATIONS Sunday, Nov. 17 Abstract #1773: Safety and Efficacy of CABA-201, a Fully Human, Autologous 4-1BB Anti-CD19 CAR T Cell Therapy in Patients with Immune-Mediated Necrotizing Myopathy and Systemic Lupus Erythematosus from the RESET-MyositisTM and RESET-SLETM Clinical Trials 3:30-3:45 PM, Room 145AB Monday, Nov. 18 Abstract #2577: Efficacy and Safety of ABBV-599 (Elsubrutinib and Upadacitinib Combination) and Upadacitinib Monotherapy for the Treatment of Systemic Lupus Erythematosus: Results Through 104 Weeks in a Long-Term Extension Study 1:30-1:45 PM, Room 146AB Abstract #2580: Safety and Efficacy of Subcutaneous Ianalumab (VAY736) for up to 68 Weeks in Patients with Systemic Lupus Erythematosus: Results from Phase 2 Study 2:15-2:30 PM Room 146AB Tuesday, Nov. 19 ***LATE-BREAKING ABSTRACT*** Abstract #L16: Dapirolizumab Pegol Demonstrated Significant Improvement in Systemic Lupus Erythematosus Disease Activity: Efficacy and Safety Results of a Phase 3 Trial 8:00-9:30 AM, 146AB POSTERS Saturday, Nov. 16 Poster Session A, 10:30 AM-12:30 PM, Poster Hall: Abstract #0087: SYNCAR: An Engineered IL-2/IL-2R-system That Selectively Enhances CD19 CAR T Cells to Deplete B Cells and Provide Therapeutic Benefit in SLE and RA Mouse Models Without Lymphodepletion Abstract #0324: Correlative Studies of CABA-201, a Fully Human, Autologous 4-1BB Anti-CD19 CAR T Cell Therapy in Patients with Immune-Mediated Necrotizing Myopathy and Systemic Lupus Erythematosus from the RESET-MyositisTM and RESET-SLETM Clinical Trials Abstract #0620: Clinical Efficacy and Patient-Reported Outcomes in Anti-Ro/Sjögren's Syndrome–Related Antigen a Antibody–Positive Patients with Active SLE Treated With Deucravacitinib in the Phase 2 PAISLEY Trial Abstract #0659: Obinutuzumab Benefits Patients with Active Lupus Nephritis Irrespective of Baseline Proteinuria Severity: A Post Hoc Analysis of a Phase II Trial Abstract #0662: Deucravacitinib, a First-in-Class, Oral, Selective, Allosteric Tyrosine Kinase 2 Inhibitor, in SLE: Efficacy by Baseline Demographics and Disease Characteristics in the Phase 2 PAISLEY Trial Abstract #0671: Effect of Litifilimab on Cutaneous Lupus Disease Area and Severity Index–Activity (CLASI-A) Subcomponents and Physician Global Assessment–Skin (PGA–Skin) in Patients with Cutaneous Lupus Erythematosus (CLE) in a Phase 2 Study Sunday, Nov. 17 Poster Session B, 10:30 AM-12:30 PM, Poster Hall: Abstract #1496: Dysregulated Serum Cytokines in Association with Clinical Manifestations in Patients with Systemic Lupus Erythematosus Abstract #1552: Kinetics of Mucocutaneous and Musculoskeletal Responses to Deucravacitinib in Patients with Active SLE in the Phase 2 PAISLEY Trial Abstract #1553: Safety, Pharmacokinetics, Clinical Efficacy and Exploratory Biomarker Results from a Randomized, Double-Blind, Placebo-Controlled Phase 1b Study of Enpatoran in Active Systemic and Cutaneous Lupus Erythematosus (SLE/CLE) Monday, Nov. 18 Poster Session C, 10:30 AM-12:30 PM, Poster Hall: Abstract #2425: Ianalumab Induced Durable Depletion of Circulating B Cell Subsets and Associated Changes in B Cell and Neutrophil Transcriptomic and Proteomic Profiles in Patients with Systemic Lupus Erythematosus: 52-Week Treatment Results from a Phase 2 Trial Abstract #2430: Dapirolizumab Pegol Impacts Important Immunologic Pathways in Systemic Lupus Erythematosus: Pharmacodynamic Analysis of T Cell and Antigen Presenting Cell Pathways from a Phase 2b Trial About Lupus Lupus is a chronic, complex autoimmune disease that affects millions of people worldwide. In lupus, the immune system, meant to defend against infections, produces autoantibodies that mistake the body's own cells as foreign, causing other immune cells to attack organs such as the kidneys, brain, heart, lungs and skin, as well as blood and joints. Ninety percent of people with lupus are women, most often diagnosed between the ages of 15-45. Black, Latinx, Indigenous, Asian and Pacific Islander people are disproportionately affected by lupus and more likely to experience severe lupus symptoms. About the Lupus Research Alliance The Lupus Research Alliance is the largest non-governmental, non-profit funder of lupus research worldwide. The organization aims to transform treatment by funding the most innovative lupus research, fostering diverse scientific talent, and driving discovery toward better diagnostics, improved treatments and ultimately a cure for lupus. Because the Lupus Research Alliance's Board of Directors funds all administrative and fundraising costs, 100% of all donations goes to support lupus research programs. For more information, please visit the LRA at LupusResearch.org and on social media at: X, Facebook, LinkedIn, and Instagram. About Lupus Therapeutics Lupus Therapeutics, the clinical research affiliate of the Lupus Research Alliance, aims to accelerate the development of curative treatments for all patients living with lupus. Lupus Therapeutics collaborates with premier research institutions, biopharmaceutical partners, and those living with lupus through the unprecedented Lupus Clinical Investigators Network (LuCIN) to drive rapid and meaningful progress in treatment development. The organization elevates the patient voice, engages community stakeholders, and strives for representation of the diverse lupus community in the clinical research process with the most innovative and renowned experts throughout North America. Visit LupusTherapeutics.org for more information. This information is brought to you by the Lupus Research Alliance and is not sponsored by, nor a part of, the American College of Rheumatology. SOURCE Lupus Research Alliance WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床2期临床结果临床3期免疫疗法

2024-10-31

·凯莱英Asymchem

【行研】全球市场超百亿美元的热门靶点——BTK

BTK是BCR(B-Cell Receptor，B细胞表面抗原受体)通路的关键激酶，在B细胞抗原受体受体（BCR）的信号传导中起关键作用，而BCR信号通路对于淋巴瘤中恶性B细胞的增殖和存活至关重要。目前已发现BTK 在各种B细胞恶性肿瘤中调节着细胞增殖、存活和迁移等生命活动，BTK靶点已成为最具潜力的涉及B细胞和巨噬细胞活化的靶点之一。自从第一个BTK抑制剂伊布替尼于2013年上市以来，BTK抑制剂在血液瘤中得到了广泛应用，在该领域取得了较大成功，其疗效和安全性都得到了充分的论证，总体销售额已经达到上百亿美元。据公开资料显示，2022年全球BTK抑制剂市场规模为115亿美元，并以接近30%的增速逐年增长；据弗若斯特沙利文数据，全球BTK抑制剂市场规模预计2025年达219亿美元，2030年达251亿美元，中国BTK抑制剂的市场规模将从2022年的43亿元人民币增长至2030年的225亿元，年复合增长率达到33%。明朗和广阔的市场吸引了不少药企入局。图.全球及中国BTK抑制剂市场规模来源：Frost & Sullivan，交银国际业界习惯将BTK划分为3代产品： 1）一代BTKi为共价抑制剂：伊布替尼2013年被FDA批准上市，目前已获批MCL、CLL、WM、MZL、cGVHD共5项适应症； 2）二代BTKi同样为共价抑制剂，相较于一代产品提升了BTK的选择性因此有更好的疗效和安全性，如阿卡替尼、泽布替尼、奥布替尼； 3）三代BTKi为非共价抑制剂，可治疗对前2代BTKi耐药的C481突变。2023年礼来的吡托布替尼（Loxo-305）的3L MCL和3L CLL适应症获FDA加速批准。表1.已上市BTK抑制剂药物情况来源：根据公开资料整理全球市场来看，伊布替尼凭借先发优势和获批适应症最多，2021年达到销售峰值97.8亿美元，2022年源于竞争加剧销售额开始下滑至83.5亿美元（-14.6%）。而阿卡替尼，泽布替尼销售额高速增长，2022年阿卡替尼全球销售额达20.6亿美元（+66.2%），泽布替尼实现全球销售5.7亿美元（+159%），2023年1月泽布海外获批2L CLL/SLL适应症，带动2023前三季度全球销售额达8.7亿美元。国内市场来看，国产药品泽布替尼、奥布替尼二代BTK抑制剂凭借疗效、安全性、价格优势，公立医院市占率不断提升，且纳入医保巨额提升销售放量。以奥布替尼为例，2022年奥布替尼进入医保后，国内城市公立医院市占率从2021年2.8%提升至6.5%，截至2023上半年，市占率达12.1%。图左. 全球BTK靶点研发阶段概况图右. 中国BTK靶点研发阶段概况来源：医药魔方 2024年4月23日，赛诺菲宣布BTK 抑制剂Rilzabrutinib（SAR444671/PRN-1008）治疗持续性或慢性免疫性血小板减少症（ITP）成年患者的III期LUNA 3研究达到主要终点，并计划于今年年底前向FDA递 Rilzabrutinib的上市申请。如若Rilzabrutinib顺利获批，将成为全球第7款上市的BTK抑制剂，与已获批的BTK抑制剂的适应症不同，赛诺菲的Rilzabrutinib以ITP作为首发适应症，将是全球首款获批ITP适应症的BTK抑制剂。目前BTK抑制剂的研发方向主要为非共价BTK抑制剂，适应症也从血液瘤拓展到自免领域拓展，药物类型从小分子延伸到PROTACs类。在非共价BTK抑制剂研究领域，基于非共价的优势，目前全球的非共价（可逆）BTK抑制剂赛道也聚集了诸多企业，已有多款药物进入临床试验阶段，如LOXO-305、MK-1026、BN102（AS-1763）、HMPL-760。在适应症方面，BTK抑制剂已被证明治疗自身免疫疾病和炎症临床有效，包括原发免疫性血小板减少症（ITP）、系统性红斑狼疮（SLE）、多发性硬化症（MS）、类风湿性关节炎（Rheumatoid arthritis,RA）等，当前BTK抑制剂在自免领域的研发正如火如荼地进行。据华创证券统计，目前在自身免疫性疾病领域探索的BTK抑制剂超过20款，适应症聚焦在多发性硬化症（MS）、自发性荨麻疹、系统性红斑狼疮、类风湿性关节炎等疾病。除诺华的Remibrutinib，赛诺菲的另一款BTK抑制剂Tolebrutinib瞄准了MS，目前也在临床Ⅲ期；渤健针对MS的BIB091，艾伯维针对系统性红斑狼疮、类风湿关节炎的Elsubrutinib都已进入临床Ⅱ期。在药物类型方面，目前国内外已有多家企业开发的BTK-PROTAC进入临床阶段。NX-2127由Nurix Therapeutic开发，是first-in-class的口服BTK降解剂，目前在开展针对B细胞恶性肿瘤临床试验Ⅰ期。此外，国外还有Baylor College of Medicine开发的RC-1；Yale University的MT-802也是BTK-PROTAC产品；国内有海思科自主开发的HSK29116、百济神州开发的BGB-16673等产品。整体来说，全球针对BTK-PROTACs的临床实验尚在早期阶段，但若能成功上市，有效解决BTK患者的耐药难题， PROTACs或将成为BTK抑制剂的焦点。 References 参考资料 1.https://baijiahao.baidu.com/s?id=1774822688581233271&wfr=spider&for=pc 2.https://baijiahao.baidu.com/s?id=1798716367638420557&wfr=spider&for=pc 3.平安证券 -始于创新、强于执行力，血液瘤及自免领域管线双开花20240321 4.https://news.yaozh.com/archive/42009 5.https://xueqiu.com/6410972106/288071404?_ugc_source=ugcbaiducard

上市批准加速审批医药出海细胞疗法

100 项与 Elsubrutinib 相关的药物交易

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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
系统性红斑狼疮	临床2期	美国	AbbVie, Inc.	2019-07-25
系统性红斑狼疮	临床2期	中国	AbbVie, Inc.	2019-07-25
系统性红斑狼疮	临床2期	日本	AbbVie, Inc.	2019-07-25
系统性红斑狼疮	临床2期	阿根廷	AbbVie, Inc.	2019-07-25
系统性红斑狼疮	临床2期	澳大利亚	AbbVie, Inc.	2019-07-25
系统性红斑狼疮	临床2期	保加利亚	AbbVie, Inc.	2019-07-25
系统性红斑狼疮	临床2期	加拿大	AbbVie, Inc.	2019-07-25
系统性红斑狼疮	临床2期	哥伦比亚	AbbVie, Inc.	2019-07-25
系统性红斑狼疮	临床2期	法国	AbbVie, Inc.	2019-07-25
系统性红斑狼疮	临床2期	德国	AbbVie, Inc.	2019-07-25

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临床结果

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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


NCT04451772 (CTgov)	临床2期	系统性红斑狼疮	185	Elsubrutinib+Upadacitinib (ABBV-599 High Dose (Elsubrutinib 60 mg/Upadacitinib 30 mg) -> ABBV-599 High Dose)	廠糧膚憲鹽襯積簾願鹹(簾醖願淵網鏇鑰壓簾鏇) = 蓋醖憲築蓋醖獵糧襯憲製廠顧淵醖獵繭鏇廠遞 (製夢窪醖構網鹽廠鹽窪, 壓夢糧鑰襯獵襯膚齋製 ~ 齋夢製淵壓壓艱衊獵選) 更多	-	2025-01-14
				Placebo for Elsubrutinib+Upadacitinib (Elsubrutinib Placebo/Upadacitinib 30 mg -> Elsubrutinib Placebo/Upadacitinib 30 mg)	廠糧膚憲鹽襯積簾願鹹(簾醖願淵網鏇鑰壓簾鏇) = 鹽餘淵壓壓鹽鏇簾齋鑰製廠顧淵醖獵繭鏇廠遞 (製夢窪醖構網鹽廠鹽窪, 蓋構艱顧積鑰網網簾夢 ~ 齋遞鑰衊顧夢鬱遞鑰齋) 更多
NCT03978520 (SLEek, CTgov)	临床2期	系统性红斑狼疮	341	Placebo for upadacitinib (Elsubrutinib Placebo/Upadacitinib Placebo)	鹽膚鹽夢衊繭製夢窪窪(艱鬱獵夢廠鏇艱遞觸製) = 觸獵鏇鬱鏇鑰範憲蓋鹹糧遞艱繭齋窪鏇襯艱餘 (廠膚築齋廠選顧衊觸範, 網齋窪鹹夢廠膚壓築襯 ~ 構遞齋蓋製觸艱範鑰製) 更多	-	2023-07-21
				Elsubrutinib+Upadacitinib (ABBV-599 High Dose (Elsubrutinib 60 mg/Upadacitinib 30 mg))	鹽膚鹽夢衊繭製夢窪窪(艱鬱獵夢廠鏇艱遞觸製) = 窪壓餘蓋壓範鬱構壓簾糧遞艱繭齋窪鏇襯艱餘 (廠膚築齋廠選顧衊觸範, 構齋蓋淵簾簾鹽網鹹觸 ~ 鏇顧夢壓淵構廠壓齋鏇) 更多
NCT03978520 (SLEek, EULAR2023)	临床2期	系统性红斑狼疮	341	ABBV-599 High Dose (ELSUBRUTINIB 60 mg and UPADACITINIB 30 mg)	鑰獵襯獵廠襯鬱廠選遞(簾選蓋積廠壓廠餘憲鑰) = 觸範觸糧觸鹽簾糧遞築積遞齋築鑰壓淵製襯獵 (築鬱鹽醖構夢蓋繭繭積, (1.0 ~ 1.6)***) 更多	积极	2023-05-31
				UPADACITINIB 30 mg	鑰獵襯獵廠襯鬱廠選遞(簾選蓋積廠壓廠餘憲鑰) = 膚遞選遞觸鹹獵衊鹹鹽積遞齋築鑰壓淵製襯獵 (築鬱鹽醖構夢蓋繭繭積, (1.5 ~ 2.3)*) 更多
NCT03823378 (CTgov)	临床2期	类风湿关节炎	97	Elsubrutinib+Upadacitinib (ABBV-599 in M16-063/ABBV-599 in M16-763)	襯觸積齋顧積願範構醖(鏇選簾鹹餘顧顧鹹範築) = 製鏇遞鏇鹹鹽築餘窪鹹鑰餘艱遞窪壓築築觸齋 (獵構觸夢鬱構遞夢網醖, 範願繭艱願鬱淵網餘窪 ~ 製襯鏇淵構網壓鬱獵糧) 更多	-	2021-09-16
				Placebo for upadacitinib+Elsubrutinib (ABBV-105 60 mg/UPA Placebo)	襯觸積齋顧積願範構醖(鏇選簾鹹餘顧顧鹹範築) = 艱淵壓糧網鑰選醖觸壓鑰餘艱遞窪壓築築觸齋 (獵構觸夢鬱構遞夢網醖, 淵願繭窪醖顧窪鹹繭繭 ~ 憲範艱觸鏇製網觸製構) 更多
NCT03682705 (CTgov)	临床2期	类风湿关节炎	242	Placebo for upadacitinib (ELS Placebo/UPA Placebo)	襯鹹淵構網觸淵構憲鏇(憲鹹鏇鹹襯製醖鹹鏇蓋) = 鹽簾構壓鹹構願遞築壓淵夢鹽選繭壓觸網醖積 (網網繭鑰獵醖鑰觸醖顧, 夢夢餘積艱壓觸獵壓糧 ~ 醖廠艱範醖醖觸獵膚鏇) 更多	-	2021-05-03
				Elsubrutinib+Upadacitinib (UPA 15 mg/ELS 60 mg)	襯鹹淵構網觸淵構憲鏇(憲鹹鏇鹹襯製醖鹹鏇蓋) = 鑰憲鹽獵築蓋積築膚鬱淵夢鹽選繭壓觸網醖積 (網網繭鑰獵醖鑰觸醖顧, 廠鹹獵憲夢蓋網憲窪齋 ~ 範鏇繭範夢顧醖鬱遞構) 更多