A Phase 1, First-time-in-human, Three-part Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of GSK4527363 in Healthy Participants (Part A), Participants With Active Systemic Lupus Erythematosus (Part B), and Healthy Participants of Chinese and Japanese Descent (Part C)

This study will assess the safety, tolerability, pharmacokinetics, pharmacodynamics and immunogenicity of GSK4527363 in healthy participants (Part A), participants with active SLE (Part B), and healthy participants of Chinese and Japanese descent (Part C).

开始日期2024-09-02

申办/合作机构

GSK Plc

NCT06572384 / Recruiting临床3期

A Phase 3, Randomized, Double-Blind, Placebo Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Belimumab Administered Subcutaneously in Adults With Interstitial Lung Disease (ILD) Associated With Connective Tissue Disease (CTD)

Interstitial lung disease (ILD) is a lung condition resulting in inflammation and stiffening of the lung, often associated with connective tissue diseases (CTDs). ILD causes reduction in lung volume, shortness of breath, cough and fatigue therefore has high impact on quality of life and is also the leading cause of death in participants with these conditions. The study will assess whether treatment of CTD-ILD participants with belimumab in addition to standard therapy will result in the stabilization and/or improvement of lung function and improve symptoms associated with ILD with an acceptable safety profile.

开始日期2024-08-26

申办/合作机构

GSK Plc

NCT06411249 / Recruiting临床4期

A Phase 4, Multicenter, Prospective, Open-Label Study Describing the Efficacy and Safety of Belimumab Administered Subcutaneously in Adult Participants With Early Systemic Lupus Erythematosus

This is a prospective, open-label, single arm 3-year clinical study to describe the short-term and long-term efficacy and safety of belimumab in participants with autoantibody positive early SLE with ongoing disease activity despite stable initial SLE therapy.

开始日期2024-06-04

申办/合作机构

GSK Plc

100 项与贝利尤单抗相关的临床结果

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100 项与贝利尤单抗相关的转化医学

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100 项与贝利尤单抗相关的专利（医药）

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1,161

项与贝利尤单抗相关的文献（医药）

2024-12-31·RENAL FAILURE

Efficacy and safety of biologics, multitarget therapy, and standard therapy for lupus nephritis: a systematic review and network meta-analysis

Review

作者: Li, Zhen-Qiong ; Tian, Gui-Qing

OBJECTIVE:

This study aimed to compare the efficacy and safety of biologics, multitarget therapy, and standard therapy for the induction of lupus nephritis.

METHODS:

A systematic search of electronic databases (EMBASE, Web of Science, PubMed, Cochrane Library, and ClinicalTrials.gov) was conducted from inception to 30 August 2023. Our study included randomized controlled trials enrolling adult lupus nephritis patients treated with biologics or multitarget therapy, in comparison with standard therapy. The primary outcomes were the rates of complete renal remission (CRR) and serious adverse events (SAE). Stata 15.0 was used to conduct the network meta-analysis.

RESULTS:

Ten randomized controlled trials with a total of 1989 patients met the inclusion criteria. The network meta-analysis indicated that compared with standard therapy, multitarget therapy, obinutuzumab, belimumab, and voclosporin therapy demonstrated superior efficacy in achieving complete renal remission. Among these options, multitarget therapy had the greatest effect (OR = 2.78, 95% CI = 1.81-4.26). Regarding safety, it was observed that there were no significant statistical differences among the various treatment options. Cluster analysis revealed that both obinutuzumab and belimumab exhibited good efficacy and safety.

CONCLUSIONS:

belimumab and obinutuzumab stood out as promising treatments due to their good performance in terms of efficacy and safety. Multitarget therapy may be the most effective approach for treating lupus nephritis. However, since the study population consists exclusively of Asian patients, further research is needed to verify the efficacy of multitarget therapy in lupus nephritis patients of non-Asian descent.

2024-10-01·ENVIRONMENTAL POLLUTION

Efficacy of anthocyanin, kaolinite and cabbage leaves-derived biochar for simultaneous removal of lead, copper and metoprolol from water

Article

作者: Sarmah, Ajit K ; Karkoosh, Hasan ; Vithanage, Meththika ; Reguyal, Febelyn

Simultaneous removal of toxic elements and pharmaceutical compounds at environmentally relevant concentrations in aqueous solution is challenging. Modification of biochar using environmental materials has attracted significant attention in wastewater treatment, while pristine biochar has several limitations in the simultaneous removal of Lead (Pb²⁺), Copper (Cu²⁺), and metoprolol. We investigated the efficacy of biochar composites using waste cabbage leaves-derived biochar with kaolinite, and anthocyanin for simultaneous removal of Pb²⁺, Cu²⁺, and metoprolol from water. Using ball milling, the surface area and functional groups of adsorbents were improved via breaking the biochar grains into ultrafine particles. Ball-milled biochar derived from waste cabbage leaves significantly increased Pb²⁺, Cu²⁺, and metoprolol adsorption by 105, 71, and 213%, respectively. Results of Brunauer Emmett Teller surface area, Fourier transform infrared and X-ray photoelectron spectroscopies showed that surface area of non-milled biochar improved nearly ten-fold following ball-milling, while several oxygen containing acidic functional groups also increased. The adsorbents resulted in high removal efficiency for Pb²⁺ (162.9 mg/g) and Cu²⁺ (48.5 mg/g) in ball milled-kaolinite composite biochar (BMKB) and 76.3 mg/g (metoprolol), respectively in ball milled-anthocyanin composite biochar (BMAB). The simultaneous sorption of Pb²⁺, Cu²⁺, and metoprolol in an aqueous solution to BMAB and BMKB, showed that the adsorption capacity followed the order of Pb²⁺ >Cu²⁺ > metoprolol in both types of ball-milled biochars. BMKB achieved a high adsorption capacity for Pb²⁺ and Cu²⁺ (59 mg/g and 50 mg/g), respectively, while BMAB exhibited an adsorption capacity 22.3 mg/g for metoprolol. It was postulated that sorption of Pb²⁺, Cu²⁺ and metoprolol involved multiple adsorption mechanisms namely surface complexation, π-π interaction, H-bond, pore filling, and ion bridging. The findings of this study revealed that ball milling is a potential technology in producing a highlyefficient adsorbent to remediate multi-contaminants in aqueous solution.

2024-09-01·Neurology-Neuroimmunology & Neuroinflammation

Relapsing-Remitting Immunotherapy Responsive Small-Fiber Neuropathy

Article

作者: Oaklander, Anne Louise ; Wilder-Smith, Einar P. ; Dietliker, Nadja ; Allen, Julia

OBJECTIVES:

To expand understanding of the pathogenesis, presentations, and treatment of initially idiopathic small fiber polyneuropathy (SFN).

METHODS:

We longitudinally readministered validated metrics to track disease course and treatment responses in a previously healthy woman with acute, postinfectious, skin biopsy-confirmed, idiopathic SFN.

RESULTS:

During 5 years, viral respiratory infections triggered 3 separated episodes of acute, disabling burning hand, foot, and face pain (erythromelalgia). The initial 2 resolved with high-dose prednisone, and the third responded to repeated immunoglobulin treatments. Pregnancy with miscarriage triggered a fourth exacerbation refractory to corticosteroids and cyclosporin. Immunoglobulins restored total remission for 2 months; then, 2 rituximab doses slightly improved later flaring. Subsequently, daratumumab initiated 100-day remission later maintained by belimumab, initiated to permit another pregnancy. Remission continued after gestational week 13 all-treatment withdrawal. A week 30 fifth flare responded to plasmapheresis, with healthy birth at week 40. At 11-week postpartum, as symptoms returned, restarting belimumab restored remission maintained during ≥19 months of breastfeeding.

DISCUSSION:

This decade of tracking characterizes a relapsing-remitting course of SFN with initially separated monophasic episodes becoming more confluent, as with multiple sclerosis. This tempo and responsiveness to 5 immunotherapies suggest dysimmune causality. Validated metrics helped define the course and track treatment efficacy, particularly during pregnancy and breastfeeding.

CLASSIFICATION OF EVIDENCE:

This is a single observational study without controls. This provides Class IV evidence.

154

项与贝利尤单抗相关的新闻（医药）

2024-09-19

·CPHI制药在线

浅谈系统性硬化病治疗进展，在研疗法作用靶点、药物类型多样

关注并星标CPHI制药在线系统性硬化病（SSc），又称硬皮病，是一种以局限性或弥漫性皮肤及内脏器官纤维化或硬化为特征的自身免疫性结缔组织病，2018年5月被列入中国第一批罕见病目录。SSc常累及全身多系统，包括胃肠道、心脏、肺、肾等脏器，其中肺部受累是SSc是常见且严重的内脏损害之一，主要表现为肺间质病变（ILD）和肺动脉高压（PAH），这两者占SSc相关死亡原因的60%。根据皮肤受累范围及临床特点，SSc可分为四型：局限皮肤型SSc、弥漫皮肤型SSc、重叠综合征和无皮肤硬化型SSc。流行病学数据显示：SSc的全球总患病率为17.6/10万，发病高峰年龄在 45~65岁，女性发病率高于男性，但男性SSc患者往往病情较重，更易出现弥漫性皮肤病变、指端溃疡和肺动脉高压（PAH），预后相对较差。 SSc治疗现状 SSc发病机制复杂，包括自身免疫学说、血管病学说和胶原合成异常学说等。但由于病因未明，SSc长期以来缺乏有效的治疗手段。临床上主要通过免疫药物及一些对症治疗来控制疾病进展，环磷酰胺、甲氨蝶呤、长春新碱等免疫抑制剂抑制来免疫系统的异常反应，减轻炎症和纤维化等病理过程。硫唑嘌呤等免疫调节剂调节免疫系统的功能，减轻自身免疫反应。此外，临床上还使用非甾体抗炎药、钙剂、免疫球蛋白及糖皮质激素等对症支持来控制病情。 2019年9月，FDA批准勃林格殷格翰的Ofev（nintedanib，尼达尼布）用于延缓系统性硬化症相关间质性肺病（SSc-ILD）成人患者的肺功能下降。该药是一种口服小分子酪氨酸激酶抑制剂，通过竞争性抑制成纤维细胞生长因子受体、血管内皮生长因子受体、血小板源性生长因子受体等受体酪氨酸激酶，阻断对成纤维细胞的增殖、迁徙和转换起关键作用的信号传导，从而抑制肺纤维化病变。 2021年3月，FDA批准罗氏IL-6受体抑制剂Actemra/RoActemra（tocilizumab，托珠单抗）皮下注射液，用于延缓SSc-ILD成人患者肺功能下降的速度。这使Actemra/RoActemra成为FDA批准的第一款用于治疗SSc-ILD的生物疗法。在研SSc药物进展据不完全统计，目前全球已出现多款在研SSc新药，详见下表。在研SSc新药作用靶点多样，且药物类型也非常多样化，涉及化药、单抗、干细胞疗法等。具体品种来看，Anifrolumab是一款首创Ⅰ型干扰素受体（IFNAR1）拮抗剂，已被批准用于治疗系统性红斑狼疮。研究表明，I型干扰素能够直接影响T细胞的增殖与活化，因此，Anifrolumab作为一种中和干扰素的药物，能够减少SSc患者T细胞的活化与增值，从而达到治疗SSc的目的。目前，Anifrolumab治疗SSc的3期临床试验正在进行中。贝利尤单抗是GSK研发的一款靶向B淋巴细胞刺激因子（BLyS）的单克隆抗体，通过特异性结合BLyS抑制B细胞的存活和增殖，其静脉注射剂已被批准成人和儿童系统性红斑狼疮，以及活动性狼疮肾炎。与静脉注射相比，贝利尤单抗的皮下注射剂型具有缩短治疗时间和提高治疗便利性的潜力。目前，贝利尤单抗皮下注射液正在国内开展一项针对SSc-ILD成人患者的国际多中心（含中国）2/3期研究。 Amlitelimab由赛诺菲与ImmuNext合作开发，是一种皮下注射的全人源化、非耗竭性单克隆抗体，通过与OX40L结合，旨在恢复促炎及调节性T细胞之间的免疫稳态，从而有潜力治疗许多免疫介导及炎症性疾病。此外，amlitelimab在抑制T细胞依赖性炎症的同时，不会导致免疫细胞的清除，从而潜在避免了免疫抑制的副作用。Amlitelimab被开发用于治疗特应性皮炎、哮喘、多发性硬化、化脓性汗腺炎、SSc等自免疾病，其中针对SSc相关间质性肺疾病（SSc-ILD）的临床试验处于2期阶段。 BI 685509是一种不依赖一氧化氮的可溶性鸟苷酸环化酶（sGC）刺激剂，可增加环磷酸鸟苷（cGMP）的产生。cGMP升高与血管舒张、血管床中的适当内皮功能以及抗纤维化、抗增殖和抗炎作用相关。BI 685509可能针对导致SSc表现的基础血管病变和纤维化。目前，BI 685509针对SSc的临床试验处于2期阶段。 FT011是一种口服药物，旨在阻断GPR68蛋白受体的活性。GPR68是一种特定的G蛋白偶联受体(GPCR)，可介导与炎症和纤维化相关的信号通路，其在健康组织中处于沉默状态，但在受伤或患病后被激活。证据表明：GPR68在导致炎症和纤维化的多个下游通路中发挥作用。临床试验数据显示：FT011在改善肺功能和缓解身体残疾方面表现出显著疗效。2024年7月，FT011被EMA授予孤儿药资格，用于SSc。 RY_SW01是一款人脐带间充质干细胞来源的干细胞疗法。与传统疗法相比，脐带间充质干细胞（MSCs）可以通过多通路进行免疫调节，并分泌细胞因子达到抗纤维化的作用；安全性方面，不会引起类似免疫抑制剂带来的不良反应。2023年8月，RY_SW01治疗SSc的临床试验申请获CDE批准。 CABA-201是Cabaletta Bio开发的一款使用4-1BB共刺激信号的全人源CD19 CAR-T疗法，有望成为B细胞驱动的自身免疫性疾病的潜在治疗方法。2024年1月，CABA-201治疗SSc的1期临床试验启动。2024年3月，该药被FDA授予治疗SSc的孤儿药资格。 VUM02是中源协和自主研发的冷冻保存型干细胞制剂，是由经筛选的健康新生儿脐带组织通过体外分离、扩增、收获、冻存后制备的人脐带源间充质干细胞（UC-MSC）候选药物。2024年9月，VUM02治疗SSc的临床试验申请获CDE批准。 RJMty19是瑞顺生物基于人源化CD19-CAR全球专利开发的一款创新现货通用型第二代DNT细胞治疗候选药物被，被开发用药治疗难治性系统性红斑狼疮、复发/难治性B细胞非霍奇金巴瘤、CD19阳性成人复发/难治性B细胞急性淋巴细胞白血病和SSc等。今年9月，RJMty19治疗SSc的临床试验申请获CDE批准。此外，Blinatumomab也被开发用于治疗SSc。该药是一种双特异性抗体结构，通过结合T细胞上的CD3和B细胞上的CD19，介导T细胞与B细胞的相互作用，导致后者被前者破坏。Blinatumomab已被证实能引起血液肿瘤患者的B细胞耗竭及免疫球蛋白水平下降。 2024年6月，来自德国慕尼黑大学附属医院(LMU)血液科的Marion Subklewe等人在《European Journal Of Cancer》杂志上发表了题为"Application of blinatumomab, a bispecific anti-CD3/CD19 T-cell engager, in treating severe systemic sclerosis: A case study"的案例研究论文结果显示：Blinatumomab安全有效，治疗过程中所有剂量下的耐受性良好，SSc患者的症状得到有效改善。总结整体来看，近些年罕见病系统性硬化症（SSc)的治疗进展有限，最新获批的两款药物--尼达尼布、托珠单抗也仅被批准用于延缓系统性硬化症相关间质性肺病（SSc-ILD）成人患者的肺功能下降，并不能从根上治愈SSc。纵观在研SSc药物，其作用靶点非常多样，这从一定程度上可以看出SSc的发病机制并不十分明确。期待在药企的不懈努力下，SSc治疗早日迎来重大突破。 END END END END 【智药研习社直播预告】来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com ▼更多制药资讯，请关注CPHI制药在线▼ 点击阅读原文，进入智药研习社~

临床研究细胞疗法免疫疗法临床申请

2024-09-17

·FiercePharma

Lupus landscape 'poised for evolution' as US doctors eagerly await new entrants

Biogen's litifilimab "stands out as an especially strong competitor" to Benlysta and Saphnelo, according to Spherix Global Insights analysts. New biologics such as GSK's Benlysta and AstraZeneca's Saphnelo, along with off-label drugs, have been the mainstay for systemic lupus erythematosus (SLE) treatment for many years. However, the landscape may be about to change with the introduction of new medicines and indications from other approved treatments.That's according to Spherix Global Insights analysts who spoke to 101 U.S. rheumatologists about current and future treatments for SLE, a landscape they see as “poised for evolution.”There are several types of lupus, with SLE the most common. The condition is caused by an autoimmune disease in which the immune system attacks its own tissues, causing widespread inflammation and tissue damage. Organ damage can occur in up to 48% of people living with lupus, most within five years of diagnosis, with lupus flares also upping the risk of organ damage.GSK’s SLE drug Benlysta, which was approved by the FDA in 2011, has now become a blockbuster medicine, while AstraZeneca’s new challenger Saphnelo, FDA-approved in 2021, remains some way behind the market leader in Benlysta in terms of sales.Doctors have also relied on off-label use of other older medicines, including rituximab. However, Spherix found in a 2023 report, this use has begun to lose favor among rheumatologists as they turn to newer biologics.Now, Spherix has found that an experimental drug from Biogen, litifilimab, “stands out as an especially strong competitor” to Benlysta and Saphnelo, according to its report. Talking to rheumatologists, Spherix analysts said that they believe litifilimab’s latest midstage data, notably its 26% improvement in SRI-4 response (a measurement on how well a patient responds to treatment) over placebo, “demonstrates a superior treatment profile compared to existing biologics and other promising therapies.”There is also hope from new indications from already-approved drugs in the form of AbbVie’s blockbuster immunology drug Rinvoq, which is in phase 3 testing for SLE, and Bristol Myers Squibb’s Sotyktu, which presented positive data in SLE at the start of the year.Spherix found that these oral therapies “offer convenience for patients and may appeal to rheumatologists seeking alternative treatment options.”Getting patients to stay on them, however, can be a “challenge,” while black box warnings on JAKs (i.e., Rinvoq) “may prevent use in earlier lines of SLE treatment,” according to Spherix. Despite that, rheumatologists “are most eager to see Rinvoq approved for SLE, followed by Sotyktu and litifilimab, all of which are believed to be potentially effective for skin manifestations,” the report found.There are also other investigational contenders in the form of UCB Pharma’s dapirolizumab pegol and Idorsia’s cenerimod.All new entrants must, however, be mindful of the “dominance” of Benlysta, the analysts conclude, which “remains a preferred choice” in both SLE and lupus nephritis.

临床结果上市批准临床3期

2024-09-13

·Insight数据库

恒瑞、智翔金泰、康诺亚......国产自免药物「爆发了」!

近期，国产自免药物正上演着一场精彩的「速度与激情」。先是恒瑞医药、智翔金泰两款国产 IL-17A 单抗率先冲线、获得上市批准，接着恒瑞的 JAK1 抑制剂艾玛昔替尼在国内提交新适应症（用于治疗斑秃）的上市申请，康诺亚的司普奇拜单抗也在昨日获批上市，成为首个国产 IL-4Rα 靶向药物，可见国产自免药物迎来了密集收获期。更引人注目的是，还有不少国内药企在积极布局自免领域潜力新靶点。这让人不禁遐想，国产自免药物的未来究竟还有多少令人期待的惊喜？迎密集收获期国产自免药物新纪元此前，自免领域的主流药物是以艾伯维的阿达木单抗等为代表的 TNF-α抑制剂。而今，白介素（IL）和 JAK 靶向药物成为了新一代的自免药物。以白介素抑制剂为例，目前全球已获批上市的靶点类型，包括 IL-4R、IL-17A、IL-12/IL-23 等，而且各个细分赛道都诞生了年销售额超 10 亿美元的「重磅炸弹药物」，甚至是年销售额超百亿美元的「超级重磅炸弹」。 2023 年自免领域销售额头部产品图片来源：Insight 数据库整理现如今，国内药企也在这一领域迎来了密集收获期。 IL-4R 药物领域的头部产品是赛诺菲/再生元的度普利尤单抗，2023 年销售额高达 115.89 亿美元，尤其 2024 年上半年销售额约 66.6 亿美元，超越阿达木单抗、强生的乌司奴单抗，成为新一代自免「药王」。值得一提的是，国产首款 IL-4R 单抗已经诞生：康诺亚/石药集团的司普奇拜单抗（CM310）昨日获批上市，成为国产首款 IL-4R 单抗。根据非头对头研究数据显示，司普奇拜单抗治疗特应性皮炎的疗效优于度普利尤单抗。巨大的市场蛋糕，注定了这一领域竞争激烈。根据 Insight 数据库，目前还有 8 款国产 IL-4R 单抗处于Ⅲ期临床，包括康方生物的曼多奇单抗、智翔金泰 GR1802、恒瑞医药 SHR-1819、三生国健 SSGJ-611、康乃德生物 CBP-201 等。 IL-4R 单抗国内研发进度图片来源：Insight 数据库，统计截止 20240912 IL-17 单抗领域的头部产品是诺华的司库奇尤单抗，2023 年销售额达 49.8 亿美元。不久前，两款国产 IL-17A 单抗相继获批上市，打破了既往外资药企垄断的局面，分别是恒瑞医药的夫那奇珠单抗、智翔金泰的赛力奇单抗，均用于治疗中重度斑块状银屑病。此外，还有不少国产 IL-17A 单抗进入Ⅲ期临床，包括康方生物 AK111（古莫奇单抗）、君实生物 JS005、三生国健 SSGJ-608、荃信生物 QX002N、丽珠医药/鑫康合 XKH004。而且，百奥泰、石药集团和甘李药业还布局了司库奇尤单抗生物类似药，市场竞争激烈。 IL-12/IL-23 靶点的竞争同样激烈，这一领域的头部产品是强生 IL-12/23 抑制剂乌司奴单抗，2023 年销售额达 108.58 亿美元，以及艾伯维 IL-23 抑制剂瑞莎珠单抗，2023 年销售额同比增长 50.3% 至 77.63 亿美元。不过，由于专利到期的影响，2024 年上半年乌司奴单抗的销售额仅同比微增 1.8% 至 53.36 亿美元。反过来，瑞莎珠单抗今年上半年销售额继续同比大增 46% 至 47.35 亿美元。国内方面，也有不少药物临近商业化，其中康方生物 IL-12/23 单抗 AK101（依若奇单抗）、艾伯维 IL-23 抑制剂利生奇珠单抗均已申报上市，信达生物 IL-23p19 抗体匹康奇拜单抗（IBI112）正在递交上市申请，礼来 IL-23p19 抑制剂 mirikizumab 正在开展Ⅲ期临床。今年 4 月，翰森制药斥资超 11 亿元引进荃信生物 IL-23p19 抑制剂 QX004N 在大中华区的权益，目前该药正在开展针对银屑病的Ⅱ期临床和针对克罗恩病的Ⅰa 期临床试验。另外，乌司奴单抗生物类似药方面，百奥泰、华东医药/荃信生物均已申报上市，石药集团 SYSA-1902 也已处于Ⅲ期临床。国产 JAK 抑制剂：迪哲领跑，泽璟、恒瑞接力除白介素抑制剂外，JAK 抑制剂也是新一代的热门自免药物。目前，全球已有近 20 款 JAK 抑制剂获批上市，其中头部产品包括诺华/Incyte 的芦可替尼、艾伯维的乌帕替尼，2023 年销售额分别达 43 亿美元、39.7 亿美元。 2024 年上半年，乌帕替尼销售额继续同比增长 57.3% 至 25.23 亿美元，仅次于诺华的 IL-17 单抗司库奇尤单抗（28.52 亿美元），同期芦可替尼的销售额也达到 24.34 亿美元。国内方面，JAK 抑制剂市场竞争相当激烈。据 Insight 数据库显示，截止 2024 年 9 月 12 日，已有 10 款 JAK 抑制剂在中国获批上市，4 款 JAK 抑制剂处于 NDA 阶段，另外还有 53 款 JAK 靶点的临床阶段药品，主要适应症集中于类风湿关节炎、特异性皮炎等自免疾病。 JAK 抑制剂国内研发进度图片来源：Insight 数据库国产 JAK 抑制剂方面，迪哲医药的戈利昔替尼进度处于第一梯队（已获批上市），已于今年 6 月获批上市，单药适用于既往至少接受过一线系统性治疗的复发或难治的外周 T 细胞淋巴瘤（r/r PTCL）成人患者。但是其适应症布局主要集中在肿瘤领域，自免相关领域适应症尚未进入临床阶段。 PTCL 在所有非霍奇金淋巴瘤中生存率最低，r/r PTCL 患者的生存预后极差，针对这一群体的既往单药治疗效果极为有限，3 年生存率仅为 23%，中位总生存期（OS）仅 5.8 个月，并且该领域近十年没有创新药上市。由此，戈利昔替尼成为了全球首个且唯一作用于 JAK/STAT 通路的治疗 r/r PTCL 的新药物，突破了这一领域的临床治疗瓶颈。进度处于第二梯队（已申报上市）的国产 JAK 抑制剂，包括恒瑞医药的艾玛昔替尼（SHR0302）、泽璟制药的吉卡昔替尼（曾用名：杰克替尼）。艾玛昔替尼是恒瑞自研的新一代高选择性 JAK1 抑制剂，对 JAK1 的选择性是对 JAK2 的 16 倍，目前已在国内递交了 4 项适应症的上市申请，包括用于强直性脊柱炎、特应性皮炎、类风湿关节炎和斑秃，其中前 3 项适应症有望于 2025 年上半年获批上市，目前在自免领域是国产 JAK 抑制剂中进展最快的。吉卡昔替尼是一种新型 JAK 和 ACVR1 双抑制剂类药物，对 Janus 激酶包括 JAK1、JAK2、JAK3 和 TYK2 具有显著的抑制作用，目前除已提交治疗中、高危骨髓纤维化的上市申请外，针对斑秃、特应性皮炎、强直性脊柱炎、特发性肺纤维化、斑块状银屑病等适应症均已处于 II 期临床及以上阶段。此外，国内其他在研的 JAK 抑制剂，还包括信达生物的伊他替尼（Itacitinib）、先声药业/凌科药业的 LNK01001、科伦药业 KL130008 等。潜力新靶点层出不穷自免药物研发的故事还未结束。从 TNF-α逐渐被白介素、JAK 替代，自免药物靶点呈现出明显的代际更迭。如今，自免领域还在不断冒出潜力新靶点，吸引了跨国制药巨头和国内药企的目光。这几年，MNC 巨头频繁布局炎症性肠病（IBD）等存在巨大未满足需求的自免疾病。 IBD 终生可复发，被称为「不死的癌症」，主要包括溃疡性结肠炎（UC）和克罗恩病（CD）两种类型，目前尚无根治 IBD 的方法，且患者人数庞大。据流行病学数据显示，目前全球约有 600-800 万 IBD 患者，主要集中在欧美地区。目前，MNC 巨头在 IBD 领域的布局方向主要集中在 TL1A 和整合素 α4β7。例如，默沙东豪掷 108 亿美元收购 Prometheus Biosciences，拿下了治疗 UC 的 TL1A 单抗 PRA023；罗氏斥资 72.5 亿美元收购 Telavant，获得了治疗 IBD 的潜在首创新型 TL1A 抗体 RVT-3101。尤其是 α4β7 靶点已诞生了大药，武田制药的 α4β7 整合素抑制剂 Entyvio（维得利珠单抗）2023 年销售额超过 50 亿美元，而且在针对 UC 的头对头试验中击败了阿达木单抗。基于此，礼来进行了频繁布局，先是以 24 亿美元收购 Dice Therapeutics，获得口服α4β7 项目和 IL-17 小分子抑制剂，后又斥资 32 亿美元收购 Morphic Therapeutics，拿下口服α4β7 整合素小分子抑制剂 MORF-057。尽管当前国内药企鲜有布局 IBD 领域，但管线也深受 MNC 巨头青睐。今年 6 月，「自免一哥」艾伯维斥资超 17 亿美元引进了明济生物的临床前 TL1A 单抗 FG-M701，其中首付款达 1.5 亿美元，足见这类药物的市场潜力。全球 IBD 领域在研的热门靶点图片来源：Insight 数据库除 TL1A、α4β7 外，其他自免类药物靶点也层出不穷，并已验证了成药性，包括靶向 CD80/CD86 的阿巴西普，靶向 PDE-4 的阿普米司特、罗氟司特、克立硼罗，靶向 BAFF 的贝利尤单抗、泰它西普（BAFF/APRIL）等。目前，也有一些国内药企布局这类管线，其中济川药业引进恒翼生物的 PDE-4 抑制剂 HPP737。以及海南海灵的 PDE-4 抑制剂 Hemay005，均已处于 III 期临床。另外，荣昌生物的泰它西普是全球首款、同类首创 BLyS/APRIL 双靶点新型重组 TACI-Fc 融合蛋白新药，可「双管齐下」阻止 B 细胞的异常分化和成熟，从而治疗自免疾病，目前已获批治疗系统性红斑狼疮、类风湿关节炎，针对重症肌无力、原发性干燥综合症、免疫球蛋白 A 肾病（IgAN）和视神经脊髓炎频谱系疾病均已处于 III 期临床。结语国产自免药物的密集收获仅是序幕，商业化大战才是检验成果的试金石。在各个细分赛道上，国内药企需面对外资巨头的强劲挑战，以及国内同行的激烈竞争。与此同时，潜力新靶点的不断涌现，也为国产自免药物的崛起提供了无限可能，未来或许还有更多惊喜等待揭晓。封面来源：企业 Logo 免责声明：本文仅作信息分享，不代表 Insight 立场和观点，也不作治疗方案推荐和介绍。如有需求，请咨询和联系正规医疗机构。编辑：vvy PR 稿对接：微信 insightxb 投稿：微信 insightxb；邮箱 insight@dxy.cn 多样化功能、可溯源数据…… Insight 数据库网页版等你体验点击阅读原文，立刻解锁！

上市批准临床3期生物类似药并购

100 项与贝利尤单抗相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D03068	贝利尤单抗	L04AA26	DB08879

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
狼疮性肾炎	欧盟	GlaxoSmithKline (Ireland) Ltd.	2011-07-13
狼疮性肾炎	冰岛	GlaxoSmithKline (Ireland) Ltd.	2011-07-13
狼疮性肾炎	列支敦士登	GlaxoSmithKline (Ireland) Ltd.	2011-07-13
狼疮性肾炎	挪威	GlaxoSmithKline (Ireland) Ltd.	2011-07-13
系统性红斑狼疮	美国	GlaxoSmithKline LLC	2011-03-09

未上市

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
结缔组织病	临床3期	美国	GSK Plc	2024-08-26
结缔组织病	临床3期	中国	GSK Plc	2024-08-26
结缔组织病	临床3期	日本	GSK Plc	2024-08-26
结缔组织病	临床3期	阿根廷	GSK Plc	2024-08-26
结缔组织病	临床3期	澳大利亚	GSK Plc	2024-08-26
结缔组织病	临床3期	比利时	GSK Plc	2024-08-26
结缔组织病	临床3期	巴西	GSK Plc	2024-08-26
结缔组织病	临床3期	加拿大	GSK Plc	2024-08-26
结缔组织病	临床3期	法国	GSK Plc	2024-08-26
结缔组织病	临床3期	德国	GSK Plc	2024-08-26

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


EULAR2024	N/A	-	54	Belimumab	醖構憲範夢鏇簾鏇襯簾(鏇積築築選壓鏇鬱網餘) = 壓廠鑰鑰鑰夢遞網壓顧糧遞積獵築繭壓鹹齋鹽 (襯構遞餘鑰糧淵憲範夢 ) 更多	积极	2024-06-05
EULAR2024	N/A	怀孕	17	Belimumab	繭鹹積範襯夢餘膚齋窪(範觸選衊醖壓築廠遞築) = 製齋壓衊鹽鹹積蓋壓範選壓顧顧繭壓製構艱膚 (糧築齋醖壓範鬱鏇網蓋 ) 更多	积极	2024-06-05
				Non-Belimumab	壓製範積顧積壓獵壓膚(繭顧壓膚鹽艱壓廠鏇鏇) = 糧觸糧膚艱鹹願觸憲獵鏇鏇憲鑰鹹蓋願簾築齋 (餘鹽鑰襯淵糧觸積蓋築 ) 更多
EULAR2024	N/A	系统性红斑狼疮 BAFF cytokine	1,137	Belimumab	衊餘夢網鏇夢鹽憲製憲(衊壓蓋壓鑰構窪構願糧) = 艱築構糧廠鬱糧憲蓋範淵鬱糧觸製齋觸積蓋鹽 (顧膚艱窪鹹艱製觸夢醖 ) 更多	积极	2024-06-05
				Belimumab (Standard of Care)	衊餘夢網鏇夢鹽憲製憲(衊壓蓋壓鑰構窪構願糧) = 夢顧餘遞膚製築鑰窪鑰淵鬱糧觸製齋觸積蓋鹽 (顧膚艱窪鹹艱製觸夢醖 ) 更多
EULAR2024	N/A	狼疮	-	Belimumab	膚膚簾獵顧觸鑰窪膚憲(遞遞顧膚選鹽鹽淵衊積) = 壓醖範積鹽衊憲顧範製淵憲鏇衊壓窪衊積艱醖 (鹽願淵鬱構鹽網範窪選 )	积极	2024-06-05
EULAR2024	N/A	狼疮性肾炎 \| 系统性红斑狼疮	106	Subcutaneous Belimumab	醖鹹鹹鏇鹹憲遞觸鬱襯(襯餘憲蓋築襯餘繭積範) = PSL reduction ≥5 mg was achievable in active disease and positive C1q-binding immune complex 夢醖鏇選願齋艱壓憲繭 (製觸顧積壓範襯膚鬱餘 ) 更多	积极	2024-06-05
EULAR2024	N/A	-	-	Belimumab	網範遞醖鬱壓鹽獵築簾(襯簾襯鏇製夢遞顧廠繭) = 範壓壓膚齋製範齋遞壓鹽窪構鹽膚觸選蓋觸齋 (築廠範廠鬱廠鹽積壓鹽, 6.3)	-	2024-06-05
				Control (no belimumab exposure)	網範遞醖鬱壓鹽獵築簾(襯簾襯鏇製夢遞顧廠繭) = 衊網顧網鹽夢鑰範鏇艱鹽窪構鹽膚觸選蓋觸齋 (築廠範廠鬱廠鹽積壓鹽, 6.5)
EULAR2024	N/A	系统性红斑狼疮维持 anti-ds DNA \| RNP \| Sm ... 更多	69	Belimumab (BE)	築構獵鑰遞觸築鹽構鏇(壓壓顧鹹簾窪艱夢夢鏇) = 憲願鹹衊遞壓鹽積襯願願鬱齋築鏇餘願構夢遞 (夢壓鏇憲醖鹹築醖獵醖 ) 更多	积极	2024-06-05
EULAR2024	临床3期	系统性红斑狼疮 baseline SLE disease duration \| baseline Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) score \| baseline immunosuppressant (IS) use	3,086	Belimumab	願膚鬱廠壓遞繭齋鏇淵(築窪夢夢築膚鹽鹽網憲): OR = 1.7 (95% CI, 1.46 ~ 1.98), P-Value = <0.0001	积极	2024-06-05
				Placebo
EULAR2024	N/A	系统性红斑狼疮	-	Belimumab	壓襯構選簾遞製構膚鏇(窪衊餘窪淵艱鏇壓鏇選): HR = 0.72 (95% CI, 0.62 ~ 0.83), P-Value = <0.0001 更多	-	2024-06-05
				Placebo
NCT02347891 (BIM, CTgov)	临床2/3期	肌炎	17	Belimumab (Arm 1 (Belimumab + SoC (Randomized Phase and Open Label Phase))	憲鹽齋衊廠築醖憲築簾(築鹹鬱醖鏇選鏇範夢構) = 遞壓艱選膚構積獵蓋鬱蓋齋觸夢鑰網淵糧衊網 (構齋獵夢衊淵鹽襯鬱網, 繭餘鬱齋範鑰願製獵淵 ~ 獵壓糧鏇鬱夢蓋觸鏇壓) 更多	-	2024-02-09
				Placebo+Belimumab (Arm 2 (Placebo + SoC (Randomized Phase) Followed by Belimumab + SoC (Open Label Phase))	憲鹽齋衊廠築醖憲築簾(築鹹鬱醖鏇選鏇範夢構) = 淵範簾簾製範廠網淵網蓋齋觸夢鑰網淵糧衊網 (構齋獵夢衊淵鹽襯鬱網, 憲醖鹽憲選遞構願窪夢 ~ 糧構鏇餘餘鏇觸夢艱獵) 更多