A Randomized, Open-Label, 2-Arm, 2-Part, Parallel Group Study to Assess the Pharmacokinetic Comparability of Subcutaneously Administered Litifilimab (BIIB059) Delivered by 3 Devices (Pre-Filled Syringe, Autoinjector, or On-Body Injector) in Healthy Participants

In this study, researchers will learn how the body processes litifilimab when it is given under the skin in 3 different ways. Currently, ongoing studies utilize pre-filled syringes (PFS) that can deliver litifilimab subcutaneously (SC), also known as under the skin.
In this study, researchers want to learn more about new ways of delivering litifilimab SC using either an autoinjector (AI) or an on-body injector (OBI):
Both devices are designed to deliver litifilimab in an automatic way, especially helping patients who may not be able to use their hands very well, or who may be afraid of needles. While the AI is handheld, the OBI device works by being placed on the skin and can help deliver the highest amount of litifilimab through a single injection. The main objective of this study is to learn how the body processes litifilimab after using the AI device or the OBI device, as compared to using the PFS method.
The main questions researchers want to answer are:
* What is the highest amount of litifilimab found in the blood after dosing? How much total litifilimab is found in the blood throughout the study? Researchers will also learn more about: Any medical problems the participants have during the study
* Any injection site pain or reactions the participants may have. Any skin reactions to the OBI device
* Any changes in the participants' overall health after receiving litifilimab.
This study will be done as follows:
* Participants will be screened to check if they can join the study. The screening period will be up to 4 weeks, after which selected participants will check into their study research center.
* Participants will be randomly assigned to be in Part 1 or Part 2 of the study:
* Part 1: Participants will receive SC injection(s) of litifilimab through either the AI device or through PFS.
* Part 2: Participants will receive SC injection(s) of litifilimab through the OBI device or through PFS.
* Participants will remain at their study research center for the first 8 days. After that, there will be a follow-up period for 17 weeks during which participants return to the center a total of 6 times.
Each participant will be in the study for about 22 weeks.

开始日期2025-01-02

申办/合作机构

Biogen, Inc.

NCT06044337

/ Enrolling by invitation临床3期

A Multicenter, Open-Label, Single-Arm, Phase 3, Long-Term Extension Study to Evaluate Continuous Safety and Efficacy of BIIB059 (Litifilimab) in Adult Participants With Active Subacute Cutaneous Lupus Erythematosus and/or Chronic Cutaneous Lupus Erythematosus With or Without Systemic Manifestations and Refractory and/or Intolerant to Antimalarial Therapy

In this study, researchers will learn more about a study drug called BIIB059 (litifilimab) in participants with cutaneous lupus erythematosus (CLE). The study will focus on participants who have either active subacute CLE or chronic CLE, or both. They may also have systemic lupus erythematosus (SLE). The participants did not respond to antimalarial therapy or had problems with the treatment that made it hard to continue.
The study will enroll only those participants who have completed treatment with litifilimab in the parent study, 230LE301.
The main objective of the study is to learn more about the long-term safety of litifilimab.
The main question researchers want to answer is:
* How many participants have adverse events and serious adverse events after taking litifilimab? Adverse events are health problems that may or may not be caused by the study drug.
Researchers will also learn more about the effect of litifilimab on CLE. They will do this by measuring the symptoms of CLE over time using a variety of scoring tools. These include the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI), the Cutaneous Lupus Activity of Investigator's Global Assessment-Revised (CLA-IGA-R), and the SELENA-SLEDAI Flare Index (SFI).
Researchers will look at how litifilimab and CLE affect the quality of life of participants using a group of questionnaires. They will also look at how litifilimab affects laboratory tests and how participants' immune systems respond to litifilimab.
The study will be done as follows:
* The last visit of parent study 230LE301 will be the first visit of study 230LE305.
* All participants will receive litifilimab as an injection under the skin once every 4 weeks. Both researchers and participants will know the dose and identity of the study drug.
* Globally, the treatment period will last up to 208 weeks, or 4 years. Participants will have up to 53 study visits during this time.

开始日期2023-10-03

申办/合作机构

Biogen, Inc.

NCT05531565

/ Active, not recruiting临床2/3期

A 2-Part Seamless Part A (Phase 2)/Part B (Phase 3) Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of BIIB059 in Participants With Active Subacute Cutaneous Lupus Erythematosus and/or Chronic Cutaneous Lupus Erythematosus With or Without Systemic Manifestations and Refractory and/or Intolerant to Antimalarial Therapy (AMETHYST)

In this study, researchers will learn more about a study drug called litifilimab (BIIB059) in participants with cutaneous lupus erythematosus (CLE). The study will focus on participants who have either active subacute CLE or chronic CLE, or both. They may also have systemic lupus erythematosus (SLE). The participants did not respond to antimalarial therapy or had problems with the treatment that made it hard to continue.
The main objective of the study is to learn about the effect litifilimab has on lowering the activity of the skin disease. Researchers will measure symptoms and signs of CLE over time using a variety of scoring tools. These include the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI), the Cutaneous Lupus Activity of Investigator's Global Assessment-Revised (CLA-IGA-R), and the SELENA-SLEDAI Flare Index (SFI).
The main questions researchers want to answer are:
* How many participants have a score of 0 or 1 on the CLA-IGA-R looking at skin redness after treatment?
* How many participants have their skin disease activity go down by at least 70% as measured by CLASI?
Researchers will also learn more about the safety of litifilimab. They will study how participants' immune systems respond to litifilimab. Additionally, they will measure the effect litifilimab and CLE have on the quality of life of participants using a group of questionnaires.
The study will be split into 2 parts - Part A and Part B. Both parts will be done as follows:
* After screening, participants will be randomized to receive either litifilimab or placebo for the 1st treatment period. A placebo looks like the study drug but contains no real medicine.
* Participants will receive either litifilimab or placebo as injections under the skin once every 4 weeks.
* The 1st treatment period will be double blinded which means neither the researchers nor the participants will know if the participants are receiving litifilimab or placebo.
* This double blinded treatment period will last 24 weeks, after which the 2nd treatment period will begin.
* During the 2nd treatment period, all participants will receive litifilimab for 28 weeks.
* After completing treatment in this study, participants that qualify will be given the choice to join the Long-Term Extension study, 230LE305. If they do not, they will move into a follow-up safety period that will last up to 24 weeks.
* The total study duration for participants will be up to 80 weeks.

开始日期2022-09-13

申办/合作机构

Biogen, Inc.

100 项与利替非利单抗相关的临床结果

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100 项与利替非利单抗相关的专利（医药）

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项与利替非利单抗相关的文献（医药）

2026-04-29·INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Genetic Polymorphisms in Systemic Lupus Erythematosus and Their Clinical Implications: A Narrative Review.

Review

作者: Azizan, Elena Aisha ; Johdi, Nor Adzimah ; Rajalingham, Sakthiswary ; Egan, Audrey Matilda ; Mohd, Rozita ; Shaharir, Syahrul Sazliyana ; Zailani, Mohamed Afiq Hidayat

Systemic lupus erythematosus (SLE) is a polygenic autoimmune disorder where genetic diversity drives significant clinical heterogeneity. This review summarizes the current understanding of the roles of genetic polymorphisms in immunological dysregulation, organ-specific manifestations and therapeutic response heterogeneity in individuals with SLE. The literature was obtained from PubMed, EBSCOhost, Web of Science and Scopus. The narrative review comprised 60 publications published within the last 12 years. The research consistently identifies the major histocompatibility complex (MHC) region as the most significant genetic risk factor for the onset of autoimmunity. Genetic variants in STAT4 and IRF5 exacerbate disease progression by facilitating chronic inflammation. These genetic factors are associated with various clinical outcomes, including renal and neuropsychiatric symptoms. Polymorphisms in HLA class II, TLR7 and FBN2 are notably linked to serious consequences, including lupus nephritis (LN). Progress in targeted therapy signifies a transition to personalized medicine with medications such as anifrolumab, litifilimab, iberdomide and Janus kinase (JAK) or Cyclin-Dependent Kinase (CDK) inhibitors, demonstrating potential for targeting pathways associated with the interferon gene signature and STAT4 polymorphisms. Notwithstanding the problems presented by the heterogeneity of SLE, the identification of risk variations is anticipated to enhance predictive and therapeutic biomarkers, hence facilitating more precise and individualized disease management.

2026-01-01·The Journal of clinical and aesthetic dermatology

What's New in Cutaneous Lupus Erythematosus: Guidelines, Biologics, and Beyond.

Review

作者: Childs, Beth A ; Merola, Joseph F

OBJECTIVE:

We aim to review current treatment strategies for cutaneous lupus erythematosus (CLE) and highlight emerging therapies, evolving outcome measures, and practical considerations that may inform future management of this clinically heterogeneous disease.

METHODS:

We conducted a narrative review of the literature using PubMed to identify relevant clinical trials, observational studies, and mechanistic investigations related to CLE treatment. Emphasis was placed on studies published within the past 15 years. Expert opinion from dermatology and rheumatology was incorporated to contextualize evolving therapies and their application in clinical practice.

RESULTS:

Current management of CLE follows a stepwise framework, with antimalarials and immunosuppressants forming the foundation of systemic therapy. However, many patients experience refractory disease, especially in chronic or hypertrophic subtypes. Advances in the understanding of CLE pathogenesis have led to the development of targeted biologics and small molecule agents that modulate Type I interferon signaling, B- and T-cell activation, and inflammatory cytokine pathways. Novel tools such as Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI-A) and the Investigator Global Assessment for Cutaneous Lupus (CLA-IGA-R) are being validated to standardize disease assessment, while RNA tape sampling and real-world electronic health record (EHR)-based algorithms are enhancing research precision. Emerging therapies, such as belimumab, anifrolumab, litifilimab, deucravacitinib, and enpatoran, demonstrate promise in both clinical trials and real-world settings.

LIMITATIONS:

As a narrative review, this study is limited by the lack of systematic inclusion criteria and formal quality assessment of individual studies.

CONCLUSION:

Ongoing therapeutic innovation, guided by mechanistic insights and strengthened by the development of standardized outcome measures, is transforming the CLE landscape and advancing the goal of precision-based, durable disease control.

2025-12-01·Arthritis & Rheumatology

Pharmacodynamic Effects of Litifilimab in Lupus in a Randomized, Placebo‐Controlled Phase 2 Study: Rapid and Sustained Reductions in Type I Interferon‐Associated Gene Expression and Cytokines

Article

作者: Furie, Richard ; Milliman, Eric ; Franchimont, Nathalie ; Ferber, Kyle ; Werth, Victoria P. ; Barbey, Catherine ; Lahoud, Youmna ; Zoghbi, Jad ; Brown, Roland

Objective:

The pharmacodynamic effects of litifilimab on type I interferon (IFN) response and correlations with clinical outcomes were investigated in systemic lupus erythematosus (SLE) and cutaneous lupus erythematosus (CLE).

Methods:

Participants from part A (SLE) or part B (CLE with or without SLE) of the randomized phase 2 LILAC trial who received litifilimab (at 50 mg, 150 mg, or 450 mg) or a placebo were included. IFN gene signature (IFNGS) scores were assessed from whole‐blood samples using a 22‐gene panel in 120 and 131 participants (parts A and B, respectively). IFNα and other IFN‐regulated cytokine concentrations were measured in serum in 112 and 131 participants (parts A and B, respectively).

Results:

Most participants were IFNGS‐high at baseline (79–91%), and no baseline IFNGS‐low participant results were reported. In IFNGS‐high participants, litifilimab induced rapid, significant (nominal P < 0.05), and sustained reductions in IFNGS scores and IFNα concentrations versus a placebo for litifilimab at 450 mg in part A and for litifilimab at 150 mg and 450 mg in part B. In part A, IFNα reductions with litifilimab were correlated with clinical response measures. In part B, dose‐response relationships for IFNGS score and IFNα concentration were observed, similar to those for disease activity measured with the Cutaneous Lupus Erythematosus Disease Area and Severity Index–Activity (CLASI‐A) score.

Conclusion:

Administration of litifilimab resulted in reductions in both IFNGS scores and IFNα concentrations, pharmacodynamic effects that correlated with clinical responses. These findings support the mechanism of action of litifilimab and its continued evaluation in larger studies of patients with SLE or CLE.image

158

项与利替非利单抗相关的新闻（医药）

2026-08-30

·自免药研社

BDCA2：SLE 下一个成药靶点？全球 5 款在研管线全景深度对比

核心导读 •BDCA2是 \\ 浆细胞样树突状细胞（pDC）\\ 特异性表达的全新靶点，理论上可从源头抑制 I 型干扰素（IFN-I）产生，相比已上市的 IFNAR1 受体阻断策略，作用位置更上游、细胞特异性更强 •全球共5 款 BDCA2 靶向药物进入临床阶段，覆盖裸单抗、ADC、双功能融合蛋白三大差异化技术路径 •渤健Litifilimab为全球领跑者，是目前唯一推进至 III 期的品种，顶线数据预计 2026 年底读出，将直接验证靶点临床成药性 •国产SSGJ-626、DB-2304、GB19同步推进，其中三生国健 SSGJ-626 国产进度最快，已进入 Ib/II 期临床阶段 🔬一、SLE 治疗困局：IFN 通路成核心突破口系统性红斑狼疮（Systemic Lupus Erythematosus, SLE）是累及多器官的慢性自身免疫性疾病。不同流行病学统计口径存在差异：全球患者估计约 340 万～800 万例，中国患者约 100 万例、疾病负担居全球首位，育龄女性为高发人群。当前标准治疗以糖皮质激素、抗疟药和免疫抑制剂为基石，长期使用伴随显著的累积性器官损伤风险。生物制剂方面，贝利尤单抗（靶向 BLyS）、阿尼鲁单抗（靶向 I 型干扰素受体 IFNAR1）先后获批，但仍有相当比例患者无法实现持续缓解。根据第三方市场报告，全球狼疮药物市场 2025 年估值约 54 亿美元，预计 2035 年达约 140.5 亿美元。为什么瞄准 I 型干扰素通路？约60%~80% 的 SLE 患者存在IFN 基因签名（IFN Signature）高表达，IFN-I 通路异常激活是发病核心环节之一： 1.浆细胞样树突状细胞（pDC）通过 TLR7/TLR9 识别自身核酸 - 免疫复合物 2.大量分泌IFN-α，驱动 B 细胞活化、自身抗体产生 3.形成先天免疫→适应性免疫的异常活化环路已上市的阿尼鲁单抗在受体水平阻断 IFN-I 信号传导，首次在 III 期验证了 I 型干扰素通路的临床价值，但存在局限：不减少 IFN-I 本身的产生、广谱阻断所有细胞的 IFNAR1 可能影响抗病毒生理功能。而BDCA2 靶点直接作用于 pDC、抑制 IFN-I 的产生，理论上具备更精准的干预潜力，成为新一代 IFN 通路药物研发的核心方向。 🔬二、BDCA2 靶点深度解析：pDC 特异性的精准干预 BDCA2（全称 Blood Dendritic Cell Antigen 2，又称 CLEC4C、CD303）是一种 II 型跨膜 C 型凝集素受体，其最核心的特征是表达高度受限：几乎仅特异性表达于人类 pDC 表面，在其他免疫细胞中不表达或表达极低，这也是其理论上脱靶风险更低、安全性更优的基础。作用机制（已被体外 / 临床前研究验证）抗体结合 BDCA2 后诱导复合物快速内吞，通过与 Fc 受体 γ 链结合启动胞内信号级联：Src 家族激酶磷酸化 ITAM 基序→激活 Syk 激酶→激活 SLP65 与 PLCγ2→Ca²⁺内流→最终在转录水平抑制 IFN-I 及促炎细胞因子产生。体外研究显示，抗 BDCA2 抗体可有效抑制 TLR7/TLR9 诱导的所有 IFN-I 亚型、细胞因子和趋化因子产生，该效应在健康供者与 SLE 患者血液样本中均得到验证。人体概念验证（I 期临床） Litifilimab 的 I 期研究（NCT02106897）首次在人体中验证了靶点生物学活性： •单次给药可显著降低血液 IFN 应答基因表达，使MxA（IFN-I 活性生物标志物）趋于正常化 •可减少皮肤病变免疫细胞浸润，降低皮肤红斑狼疮疾病面积和严重程度指数活动度评分（CLASI-A） •整体安全性、药代动力学与药效学特征良好 🔬三、全球 BDCA2 靶向管线：5 款药物三大技术路径截至 2026 年 8 月，公开信息显示全球共5 款 BDCA2 靶向药物进入临床阶段，形成三条差异化技术路线。药物名称研发企业技术路径最高临床阶段核心适应症布局 Litifilimab（BIIB059）渤健（Biogen）人源化 IgG1 单抗 III 期 SLE、皮肤型红斑狼疮（CLE） DB-2304 映恩生物 BDCA2 靶向 ADC I 期 SLE、CLE SSGJ-626 三生国健人源化单抗 Ib/II 期 SLE、CLE GB19 科兴制药创新单抗 I 期 SLE、CLE LBL-047（DNTH212）维立志博 / Dianthus BDCA2/TACI 双功能融合蛋白 I 期 SLE、干燥综合征、皮肌炎 3.1 Litifilimab：赛道绝对先行者，III 期读出在即渤健开发的全球首个进入临床、目前唯一推进至 III 期的 BDCA2 靶向单抗，其 II 期 LILAC 研究结果发表于《新英格兰医学杂志》（NEJM, 2022）。 •SLE 队列（Part A）：主要终点为第 24 周肿胀压痛关节总数变化，治疗组平均减少 15.0 个，安慰剂组减少 11.6 个，达到统计学显著差异；关键次要终点 SLE 应答指数 4（SRI-4）应答率为 56%（治疗组）vs 29%（安慰剂组）。部分临床评论认为该效应量稳健，但 NEJM 同期述评同时指出，多数次要终点未能支持主要终点结果，疗效一致性仍需更大规模验证。 •CLE 队列（Part B）：主要终点为第 16 周 CLASI-A 评分百分比变化，50mg、150mg、450mg 剂量组分别为 - 24.3、-33.4、-28.0 个百分点，呈剂量效应关系；应答率从第 4 周起即与安慰剂拉开差异，起效较快。 •AMETHYST 研究：2026 年美国皮肤科学会（AAD）年会公布第二项 CLE II 期阳性结果，第 24 周时 16.3% 的患者达到 CLASI 0-3 分（无或极轻微疾病活动），安慰剂组为 0。 •III 期进展：两项全球 III 期试验 TOPAZ-1（NCT04895241）、TOPAZ-2（NCT04961567）已于 2025 年 10 月完成入组，顶线数据预计 2026 年底公布；2026 年 1 月获 FDA 突破性疗法认定（CLE 适应症）。 3.2 DB-2304：全球首款 BDCA2 靶向 ADC 映恩生物基于其 DIMAC 免疫调节型 ADC 平台开发，是全球首个进入临床的 BDCA2 靶向抗体偶联药物，首次将 ADC 概念从肿瘤领域跨界应用于自免领域。 •作用机制：双重协同 —— 抗体结合 BDCA2 直接抑制 pDC 活化；复合物内吞后在 pDC 内释放糖皮质激素受体激动剂载荷，进一步抑制促炎通路。理论上可降低激素全身暴露，减少长期激素治疗的副作用。 •临床前数据：来自 2023 年 ACR 会议摘要，显示相比裸抗体可更广泛抑制促炎细胞因子；该数据为会议摘要，未经同行评审完整发表。 •临床进展：采用澳大利亚首发 + 中美台多区域同步策略；2024 年 11 月完成全球首例给药；2025 年公布健康受试者 I 期数据，安全性耐受性良好；目前正在 SLE 患者中开展 I 期临床。 3.3 SSGJ-626：国产首个进入临床的 BDCA2 单抗三生国健自主研发的重组抗 BDCA2 人源化单抗，国产同靶点进度最快，采用中美双报策略。 •临床进展：Ia 期剂量爬坡完成；Ib 期多中心研究（CTR20253492）于 2026 年 3 月完成全部入组；根据公司 2026 年半年报，计划 2026 年下半年启动 SLE II 期临床，CLE II 期同步推进；美国 IND 已获批。 •药效学信号：公司半年报披露，SLE 患者给药后观察到 IFN-α 呈剂量依赖性持续抑制；该指标为药效学生物标志物，不等同于临床疗效，最终获益需 II/III 期验证。 3.4 GB19：主打长效差异化设计科兴制药子公司深圳科兴药业自主研发的 BDCA2 靶向创新生物药。 •差异化特征：公司披露临床前研究显示靶点抑制时长超 90 天，有望降低给药频率；该数据为临床前研究结果，人体实际药效持续时间仍需临床验证，目前无公开头对头对比数据。 •临床进展：2026 年 2 月获 NMPA 临床批准（SLE 适应症），3 月获 FDA 临床批准，6 月完成 I 期首例受试者入组，采用中美双报策略。 3.5 LBL-047：全球首个 BDCA2/TACI 双功能融合蛋白维立志博自主研发，同时靶向pDC（BDCA2）与B 细胞（TACI）两条致病通路。 •分子设计：由人源化抗 BDCA2 抗体与工程化 TACI 胞外域组成，Fc 区引入突变延长半衰期；理论上可同时抑制 IFN-I 产生与 B 细胞活化增殖。 •临床进展：2025 年 9 月获 FDA IND 批准；2025 年 12 月启动 I 期临床；2025 年与 Dianthus Therapeutics 达成海外权益合作，交易总金额约 10 亿美元；2026 年确定优先适应症为干燥综合征、SLE 和皮肌炎。 •临床前数据：来自 2024 年 EULAR 会议摘要，显示可同时抑制 pDC 和 B 细胞功能；未经同行评审完整发表。 🔬四、国内外管线深度对比：四大维度客观比对 4.1 研发进度：渤健领跑，国产紧随其后 Litifilimab是目前唯一进入 III 期的品种，2026 年底的顶线数据是整个靶点的关键验证节点。国产管线中SSGJ-626 进度领先（Ib 期完成、II 期启动在即），DB-2304、GB19、LBL-047 均处于 I 期临床阶段。 4.2 技术路径：三条路线各有优劣技术路线代表药物理论优势潜在风险与不确定性裸单抗 Litifilimab、SSGJ-626、GB19 技术最成熟、成药性确定性最高、开发风险最低作用机制相对单一，疗效可能存在天花板 ADC DB-2304 精准细胞递送载荷，理论上比裸单抗作用更广谱自免领域 ADC 无上市先例，载荷全身暴露、安全性与工艺复杂度待验证双功能融合蛋白 LBL-047 双通路协同，有望实现更深的疾病控制分子成药性更复杂，免疫抑制更强，感染风险可能更高 4.3 适应症布局：CLE 成为差异化竞争焦点 5 款药物均以SLE为核心适应症，但皮肤型红斑狼疮（CLE）正成为竞争焦点 —— 目前 CLE 尚无任何靶向治疗药物获批，临床需求高度未满足。 •Litifilimab 在 CLE 领域布局最深，两项 II 期阳性结果 + FDA 突破性疗法认定 •国产 SSGJ-626、GB19、DB-2304 均同步布局 SLE+CLE 双适应症 •LBL-047 适应症布局最广，覆盖干燥综合征、皮肌炎等多类 IFN 相关疾病 4.4 全球化布局：国产企业同步出海渤健 litifilimab 已推进至中国 III 期临床。国产企业普遍采用中美双报 / 全球多中心策略：SSGJ-626 美国 IND 已获批、DB-2304 澳中美台四地同步、GB19 中美双报、LBL-047 通过授权合作实现海外权益开发。 BDCA2 作为尚无药物获批的全新靶点，为中国企业提供了与跨国药企同台竞争的时间窗口。 🔬五、BDCA2 vs IFNAR1：IFN 通路的两条路径两者同属 I 型干扰素通路干预药物，但作用层次存在本质差异：上游源头抑制 vs 下游受体阻断，并非直接的优劣替代关系。对比维度阿尼鲁单抗（已上市，IFNAR1） Litifilimab（III 期，BDCA2）作用层次受体水平阻断所有 IFN-I 信号传导 pDC 水平抑制 IFN-I 的产生理论特点全面阻断 IFN 效应细胞特异性更强，更接近病理源头关键 III 期数据 TULIP-2：BICLA 应答率 48% vs 32% TOPAZ 研究：待 2026 年底读出皮肤病变有改善 II 期数据显示改善更显著关节病变有改善 II 期数据显示显著减少长期器官保护 208 周随访确证器官损伤减少待验证主要安全风险上呼吸道感染、支气管炎、带状疱疹 II 期报告带状疱疹、疱疹性角膜炎客观说明：BDCA2 在皮肤病变中的疗效信号更突出，可能与 pDC 在皮肤组织中富集相关；两者并非必然竞争关系，联合使用或可实现更深程度的通路抑制，但感染风险也可能叠加，目前尚无联合治疗研究数据。 🔬六、挑战与展望：靶点验证前夜的机遇与风险核心挑战 1.III 期成药性验证是关键：SLE 领域不乏 II 期阳性、III 期失败的案例。litifilimab 的 TOPAZ 研究结果将直接决定 BDCA2 靶点的临床价值：若成功，靶点将迎来价值重估；若失败，则需审慎区分是靶点本身还是药物 / 试验设计问题。 2.感染风险是核心安全红线：IFN 通路抑制天然伴随感染风险，pDC 在抗病毒免疫（尤其疱疹病毒、呼吸道病毒）中作用重要，长期抑制的安全性需持续监测；ADC、双功能蛋白等更强免疫抑制的分子，风险监测尤为重要。 3.患者分层有待优化：IFN 基因签名高表达患者更可能从该类治疗获益，基于生物标志物的精准分层是提升疗效信号的重要策略。未来展望 •若 litifilimab III 期成功，BDCA2 将成为继 IFNAR1 之后第二个在 SLE 中获得 III 期验证的 IFN 通路靶点 •CLE、皮肤受累突出的 SLE 亚群，是 BDCA2 药物差异化突破的核心细分领域 •国产管线凭借本土市场 + 全球化布局，有望在靶点验证后快速跟进 •BDCA2 与 B 细胞靶向、IFNAR 阻断的联合治疗，是长期探索的重要方向 🔬七、总结 BDCA2 是继 IFNAR1 之后，I 型干扰素通路中第二个具备成药性潜力的靶点，通过 pDC 特异性的源头抑制，理论上实现了更精准的 IFN 通路干预。全球 5 款临床阶段药物形成裸单抗、ADC、双功能融合蛋白三条差异化技术路径。渤健 litifilimab 领跑全球，III 期数据 2026 年底读出，是赛道决定性里程碑。国产阵营中，三生国健 SSGJ-626 进度最快，映恩生物 DB-2304 以 ADC 差异化突围，科兴 GB19 主打长效特征，维立志博 LBL-047 布局双靶点，整体已跻身全球同靶点第一梯队。 2026 年底的 III 期数据读出，将正式开启 BDCA2 赛道的 “验证后竞争” 时代。信息数据来源 1.渤健、三生国健、映恩生物、科兴制药、维立志博官方公告 2.[ClinicalTrials.gov](ClinicalTrials.gov)、中国药物临床试验登记与信息公示 3.《新英格兰医学杂志》、《临床研究杂志》（JCI）、《风湿病学年鉴》（ARD）等 4.AAD 2026、ACR 2023、EULAR 2024、AIC 2025 公开报告 5.Verified Market Reports、Market Research Future 第三方行业报告免责声明本文基于公开信息整理，仅供行业研究与学术交流参考，不构成任何诊疗建议、用药指导或投资决策依据。在研药物的临床前数据、早期临床数据不代表最终临床疗效；药物研发存在固有不确定性，适应症获批、临床进展与商业化节奏均可能发生变化，具体以监管机构批准文件与企业官方披露为准。 END 📌免责声明：本文仅为医药行业研发信息梳理，仅作知识交流与分享，不涉及商业宣传，不构成任何诊疗建议、用药指导或投资决策。文章如有侵权请联系删除。三生国健（Sunshine Guojian Pharmaceutical）|领先的中国抗体药公司|自身免疫领域全域管线布局自免领域中国创新药企Top10|特应性皮炎AD在研临床管线进展分析（截止2026年8月） BMS 守城、武田进攻、Alumis 突围：三款口服 TYK2 抑制剂同台拆解 Clinical-stage Biotech Beeline Medicines：BMS 分拆自免新锐，TLR7/8 赛道的机遇与不确定性 2026年8月全球跨国药企特应性皮炎（Atopic Dermatitis, AD）在研临床管线进展 2026年8月中国创新药企系统性红斑狼疮（SLE）在研临床管线进展截止2026 年 8 月 PROTAC 在自身免疫疾病领域的全球在研临床管线进展 2026年8月全球跨国药企系统性红斑狼疮（SLE）在研临床管线总结 PROTAC在自身免疫性疾病领域的前沿研究全球16家核心跨国药企自身免疫领域临床管线汇总炎症性肠病 TL1A 靶点：从 II 期到 III 期阳性结果：默沙东（MSD）Tulisokibart IBD 临床试验回溯日本跨国药企|小野制药（ONO PHARMACEUTICAL）在自免领域的商业+在研管线 Top15 跨国药企2026 年H1自免领域商业化表现、当前研发布局及产研匹配度 Regeneron（再生元制药）自身免疫与炎症领域管线布局全球反义寡核苷酸（ ASO）先驱Ionis Pharmaceuticals在自身免疫与免疫介导领域的管线布局全球 RNA 干扰（RNAi）领域先驱Alnylam Pharmaceuticals 自身免疫领域管线布局靶向补体C5的GalNAc偶联siRNA疗法Cemdisiran：全身性重症肌无力临床全阶段数据与全球开发进度全球首个获批 FcRn 抑制剂的Biotech：argenx SE 自身免疫疾病领域管线布局小核酸药物（siRNA、ASO）在自免领域的前沿布局自免领域全球首个靶向BAFF/APRIL IgAN III期（ORIGIN 3）中期数据证实蛋白尿显著改善全球自免药市场迎来亚洲创新力量亚洲头部创新药企|恒瑞医药自免领域的商业+临床管线布局【版权说明】：本公众号欢迎个人分享朋友圈或大群，但谢绝媒体或机构未经授权转载至其他平台。

2026-08-28

·FiercePharma

Biogen enlists lupus patient advocate to share social media story of resilience

Biogen’s late-stage lupus candidates may not have crossed the FDA finish line yet, but the company has already hit the ground running with its patient advocacy work. A new social media tie-up featuring lupus patient advocate Naomi Rose highlights her journey navigating the chronic autoimmune disease cutaneous lupus erythematosus (CLE), emphasizing the importance of connecting with community in the disease space. “Lupus has taught me resilience,” she says in the 54-second video . “Some days I have hope and some days it is hard to have hope.” The video continues with clips of Rose living her day-to-day life; working out, setting up her camera to film and spending time with her son. As she discusses the power of social media content and building community, a montage of video content from her own social media plays, flashing through a barrage of meaningful moments that she’s posted online. “These are real people, with real experiences that can actually relate,” Rose says, referring to the community of lupus patients she’s found by sharing her experience on social media. “And it just makes me happy to connect and find community within that. That is what keeps me going.” The video ends with Biogen’s “making breakthroughs happen” tagline, but this time with “in lupus” added in a different font. “Behind every lupus diagnosis is a person, a story, and a community,” Biogen wrote in its Facebook caption for the video. On Instagram, the company uses a different caption introducing Rose’s journey of “resilience, hope, and finding strength through community," further inviting its audience to “hear how connection and shared understanding have shaped her journey.” Outside of her work as a patient advocate for lupus nonprofit organizations such as 50 Shades of Pain and We Are ILL , Rose works in influencer marketing herself as a brand partnerships coordinator for an Atlanta-based creator, according to her LinkedIn. She has also amassed a large following on her own social media pages , where she posts motherhood and travel content on her personal page, plus lupus advocacy content on her lupus-specific page , Lupus Living Diaries. Biogen has enlisted several patient advocates so far in the lupus space, who have shared their stories as the company continues to study its two lupus candidates. The drugmaker is working on what it says could be the “first lupus portfolio in the industry” and developing treatments for both systemic lupus erythematosus (SLE) and CLE. Earlier this year, Biogen’s litifilimab earned a breakthrough therapy designation in CLE from the FDA, adding more weight to what the company hopes to be the first advanced therapy specifically approved to treat the disease subtype. Litifilimab is currently in phase 3 trials for CLE and SLE, with a data readout in CLE expected in 2027. In SLE, Biogen’s litifilimab studies were specifically designed to enroll participants that accurately reflect the U.S. lupus patient population, as the disease disproportionately impacts young women, especially in communities of color. Biogen often spotlights patient advocates on its social media, with recent posts including a celebration of spinal muscular atrophy (SMA) awareness month and a series of patient and caregivers sharing their Alzheimer’s disease stories. Earlier this summer, the company launched a campaign highlighting the “patient journey of individuals who have grown up with SMA,” using images shot from a lower angle to redefine how people view those who use assistive devices, Biogen told Fierce at the time.

临床3期突破性疗法

2026-08-23

·丁香园 Insight 数据库

渤健不再只做渤健

在医药江湖中，渤健应该算是那种出身名门、师承显赫、内功深厚，但近几年总被外界追问「你到底还能不能打」的老牌高手。曾经，渤健凭借多发性硬化症（MS）产品组合，一跃成为全球知名 Biotech，而后又通过诺西那生在罕见病领域证明了自己的实力。可惜当明星产品渐渐老去，寄予厚望的阿尔茨海默病新药又接连受挫，渤健突然发现自己熟悉的战场正在变窄。于是，渤健开始做一件颇有意思的事情：它不再只把命运押在神经科学上，而是将业务触角向自免、肾病等领域延伸。Insight 数据库显示，目前渤健神经科学之外的在研新药资产占比已经接近半数，涉及适应症包括红斑狼疮、lgA 肾病、膜性肾病等等。老本行不香了？回看过去，渤健当然有资格骄傲。它由一批全球顶尖科学家联合创立，其中不乏诺贝尔奖主级别的人物，比如 Walter Gilbert、Phillip Sharp。更重要的是，渤健不是那种只会讲故事，却拿不出产品的公司。 1996 年以来，渤健推出了一系列重磅 MS 新药，包括 Avonex（干扰素β-1a）、Tysabri（那他珠单抗）、Plegridy（聚乙二醇干扰素β-1a）、Tecfidera（富马酸二甲酯）等。凭借这些产品，渤健长期占据神经科学领域的重要位置。另外，渤健还在积极开发针对脊髓性肌萎缩症、阿尔茨海默症、抑郁等疾病的新药，也都有相关产品进入市场，比如 Spinraza（诺西那生）、Leqembi（仑卡奈单抗）、Zurzuvae（舒拉诺龙）。从渤健近十年财报来看，神经科学领域一直是它的现金流底座，占总营收比例高达 70%，尤其是 MS 药物，贡献了一半左右的收入。其余则主要来自生物类似药，以及 CD20 项目（Rituxan/Gazyva）的合作分成。 2019 年最辉煌时，渤健总营收甚至达到了 143.78 亿美元，净利润也有 58.89 亿美元，这主要得益于 Tecfidera、Tysabri、Spinraza 三大畅销产品的推动。可惜江湖上没有永远的独门绝技。受市场竞争和专利悬崖的影响，从 2020 年开始，渤健的收入一路下滑，直到 2025 年才有小幅回升，全年营收 98.91 亿美元。不过此时，渤健曾经的支柱产品 Tecfidera 年销售额仅余 6.8 亿美元，与巅峰时期相比直接蒸发了 37 亿美金。Tysabri、Spinraza 也都逐年下滑。另外，老牌产品 Avonex 的销售额持续萎缩，2025 年仅销售 6.96 亿美元。渤健核心产品的销售额表现（单位：亿美元）来源：丁香园如果只是 MS 产品衰退，渤健还不至于陷入成立以来最严重的业务低谷期。阿尔茨海默病新药 Aduhelm 的失利，给了它最后一击。2021 年 6 月，Aduhelm 获得 FDA 加速批准，打破了阿尔茨海默病领域近 20 年没有新药获批的困局，可惜后续因疗效争议商业化惨败。这款产品直接将渤健拉入了历史级谷底。老产品下滑，新产品爬坡，Aduhelm 又遗憾退场，痛定思痛之下，渤健开始转身，寻找新的价值高地。打造新渤健如果说旧渤健靠神经科学成名，那么新渤健就要靠不只做神经科学活下去。 2022 年 5 月，Chris Viehbacher（魏巴赫）接任渤健 CEO。他被业内称为微笑杀手，在赛诺菲就职期间，曾大刀阔斧重组改革，操刀过多起成功并购案例，包括把健赞（Genzyme）纳入麾下、深化与再生元的合作等。这样一位 CEO 来到渤健，本身就带着某种信号：变革！不出所料，在魏巴赫的带领下，渤健迅速开启了大象转身式的重塑。一方面，渤健通过 Fit for Growth 计划降本增效，具体包括砍掉 Aduhelm 在内的大批高风险或缺乏商业前景的临床项目，以及裁员上千人，全面精简组织架构。另一方面，渤健通过重金并购成熟资产与广泛布局早期平台的双轨战略，不断丰富产品管线，拓展业务边界。正所谓，资金流向在哪里，战略核心就在哪里。Insight 数据库显示，2022 年以来，渤健作为买方已经达成了近 30 起 BD 交易。把这些交易放在一起看，可以发现一个明显特征：在丰富神经管线的同时，渤健正以高频、重金的强侵略性交易，切入自免、肾病、罕见病等高价值疾病领域。来源：丁香园 2023 年 7 月，渤健宣布 73 亿美元收购 Reata。此前渤健的商业底盘高度依赖 MS 产品，这笔交易不仅给它带来了一个可以独立贡献收入的罕见病资产——弗里德赖希共济失调症新药 Skyclarys，同时还获得了多条早期研发管线，包括 RORγ 反向激动剂 RTA 1701、NRF2 后续分子 RTA 417 和 RTA 415 等。 2024 年，渤健又通过收购 HI-Bio，把免疫学和肾病管线推到了台前，核心产品是 CD38 单抗菲泽妥单抗。同年，它还与 Neomorph 达成了新药研发合作，发现和开发用于阿尔茨海默病、罕见神经疾病和免疫疾病的分子胶降解剂。 2025 年之后，这个信号变得更加明显。渤健不仅通过收购，获得了 2 款已上市的补体抑制剂：EMPAVELI（pegcetacoplan）、SYFOVRE（pegcetacoplan 玻璃体腔注射剂），以及一系列免疫管线，还引进了不少在研新药和前沿技术平台，包括下一代口服小分子 C5aR1 变构拮抗剂 VQ-201、SCN1A ASO 疗法佐瑞那生，以及 AntiClastic™ ASO 平台、Hybrozyme™ 皮下注射技术等。除传统 BD 外，为了扭转过去过度依赖内部研发导致的效率低、风险高问题，渤健还启动了开放式创新战略，成立 New Ventures（新创投团队），由前 Atlas Venture 合伙人领衔，直接在极早期（如源头科学、临床前阶段）进行股权投资或设立管线孵化项目。增长新动力锐意改革之下，渤健已经从一家以神经科学为核心的公司，逐渐向神经、免疫、罕见病三条主线并行转变。不过，这并不意味着渤健已经走出了阵痛期。MS 老产品仍在下滑，外部交易投入短期内也会影响利润表现，但好在 Leqembi（治疗阿尔茨海默症）、Zurzuvae（治疗抑郁）、Skyclarys（治疗弗里德赖希共济失调）、Syfovre（治疗地图状萎缩）、Empaveli（治疗阵发性睡眠性血红蛋白血症）等新兴产品开始发力，让渤健重新回到了增长渠道。 2026 年上半年，渤健营收 52.14 亿美元，与去年同期相比增长了 3%。值得注意的是，今年第二季度，该公司的增长型产品销售额首次超过传统 MS 组合，成为其业绩增长的核心驱动力。随着新上市产品开始贡献业绩增量，渤健旗下其他在研新药同样展现出不俗的商业潜力。Insight 数据库显示，渤健目前在研的临床阶段新药有 30 多款，其中处于临床后期（III 期及 II/III 期）的占比超过 30%，储备极其丰厚，而且这些项目不再集中在单一神经科学领域，而是恰好对应神经、免疫、罕见病三条主线。免疫学管线中，最值得关注的是 BDCA2 单抗 litifilimab 和 CD40L 单抗 Dapirolizumab Pegol，均推进到了 III 期临床阶段。根据渤健最新财报，litifilimab 预计今年就会读出针对系统性红斑狼疮（SLE）的 III 期 TOPAZ-1 和 TOPAZ-2 研究数据，明年读出针对皮肤型红斑狼疮（CLE）的 AMETHYST 研究数据。来源：丁香园 Insight 数据库神经和罕见病领域，也都有新产品推进到了 III 期临床，比如 Dravet 综合征药物佐瑞那生、脊髓性肌萎缩症药物 Salanersen 等。佐瑞那生是全球首创 ASO 疗法，预计在 2027 年读出数据，如果临床结果积极，有望成为渤健继 Spinraza 和 Qalsody 之后，在遗传性神经疾病领域继续扩张的一个重要项目。总之，渤健正在用新产品修复收入，用后期管线争取下一轮产品周期，再用外部合作和早期技术为更远期的增长保留选择权。结语旧渤健相信科学，相信高难度疾病，相信一款重磅产品可以重新定义公司。新渤健仍然相信科学，但它显然变得更现实：要控制成本，要买入外部资产，要让产品组合更分散，要让管线风险更可控，也要让公司不再被单一疾病领域定义。参考资料： 1. 渤健官网、官微、历年财报 2. 渤健维基百科 3. 丁香园 Insight 数据库 4. The Rocky Road from Startup to Big-Time Player: Biogen’s Triumph Against the Odds（Lawrence M. Fisher，发表于 1997 年）编辑：月牙封面来源：站酷海洛免责声明：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。

100 项与利替非利单抗相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D12232	-	-	-

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
皮肤红斑狼疮	临床3期	美国	Biogen, Inc.	2023-10-03
皮肤红斑狼疮	临床3期	中国	Biogen, Inc.	2023-10-03
皮肤红斑狼疮	临床3期	日本	Biogen, Inc.	2023-10-03
皮肤红斑狼疮	临床3期	阿根廷	Biogen, Inc.	2023-10-03
皮肤红斑狼疮	临床3期	比利时	Biogen Idec Research Ltd.	2023-10-03
皮肤红斑狼疮	临床3期	巴西	Biogen, Inc.	2023-10-03
皮肤红斑狼疮	临床3期	保加利亚	Biogen, Inc.	2023-10-03
皮肤红斑狼疮	临床3期	加拿大	Biogen, Inc.	2023-10-03
皮肤红斑狼疮	临床3期	智利	Biogen, Inc.	2023-10-03
皮肤红斑狼疮	临床3期	哥伦比亚	Biogen, Inc.	2023-10-03

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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


NCT02847598 (LILAC \| LILAC study, CTgov)	临床2期	皮肤红斑狼疮 \| 系统性红斑狼疮 \| 盘状红斑狼疮	264	Placebo (Part A: Placebo)	鏇獵積獵築願糧衊構壓(廠醖艱觸艱鹹廠憲鬱遞) = 積夢築鹹鑰衊糧選蓋鹹齋廠衊願繭餘壓觸夢願 (鹽獵夢壓鏇窪窪餘艱觸, 10.3) 更多	-	2023-05-15
				BIIB059 (litifilimab) (Part A: BIIB059 450 mg)	鏇獵積獵築願糧衊構壓(廠醖艱觸艱鹹廠憲鬱遞) = 範鹹夢獵顧衊築製構廠齋廠衊願繭餘壓觸夢願 (鹽獵夢壓鏇窪窪餘艱觸, 8.7) 更多
NCT02847598 (LILAC, Pubmed \| N Engl J Med)	临床2期	系统性红斑狼疮 BDCA2	132	Litifilimab 450 mg	憲窪壓選壓襯繭糧製膚(築構衊醖鏇艱鏇餘廠構): P-Value = 0.04 更多	积极	2022-09-08
				Placebo
NCT02847598 (LILAC, Pubmed \| N Engl J Med)	临床2期	皮肤红斑狼疮	132	Litifilimab 50 mg	壓蓋積選鹹獵願構齋遞(製簾膚遞鹽鹽憲簾範窪) = Litifilimab was associated with one case of herpes zoster infection 鬱遞積糧蓋獵獵齋鹹醖 (鬱觸鏇積鑰範獵膚製蓋 ) 更多	积极	2022-07-28
				Litifilimab 150 mg
NCT02847598 (LILAC, EULAR2022)	临床2期	系统性红斑狼疮 anti-nuclear antibodies \| anti-double-stranded DNA antibodies	-	BIIB059 450 mg	餘醖糧願獵淵遞顧鏇鹽(鬱餘齋構遞鬱願獵構壓) = 顧醖夢顧顧構鹽憲廠憲願簾選淵鹽鹽鑰觸醖夢 (衊廠觸構構鏇積鹹窪衊 ) 更多	积极	2022-06-01
				Placebo	餘醖糧願獵淵遞顧鏇鹽(鬱餘齋構遞鬱願獵構壓) = 遞鬱鏇繭鬱鬱獵襯積顧願簾選淵鹽鹽鑰觸醖夢 (衊廠觸構構鏇積鹹窪衊 ) 更多
NCT02847598 (LILAC study, EULAR2022)	临床2期	皮肤红斑狼疮 BDCA2	-	BIIB059	餘鏇願鬱蓋艱壓艱選顧(廠鹽鑰窪憲鑰獵製鹽簾) = 構夢範顧積願鬱簾醖糧觸襯製簾醖齋獵夢築艱 (襯淵顧憲鏇夢築襯膚艱 ) 更多	积极	2022-06-01
NCT02847598 (LILAC, ACR2020) 人工标引	临床2期	系统性红斑狼疮	120	BIIB059	鹹餘蓋糧壓憲膚艱選糧(簾齋窪製獵積積顧齋淵) = 醖壓齋遞餘艱願艱糧構積構廠窪壓簾選觸糧製 (鏇壓選襯築遞遞夢顧鏇, 1.2) 更多	积极	2020-11-07
				Placebo	鹹餘蓋糧壓憲膚艱選糧(簾齋窪製獵積積顧齋淵) = 窪醖鬱廠醖獵膚鏇襯鑰積構廠窪壓簾選觸糧製 (鏇壓選襯築遞遞夢顧鏇, 1.3) 更多
NCT02847598 (LILAC, EULAR2020)	临床2期	皮肤红斑狼疮	132	BIIB059 50 mg	夢窪簾餘窪遞鬱製鏇獵(壓網窪壓構範選齋襯襯) = 62 (62.6%) 80 (60.6%) 憲鹹願製簾獵選憲簾鹽 (窪觸積遞淵遞鹹艱積簾 ) 更多	积极	2020-06-03
				BIIB059 150 mg
NCT02847598 (Pubmed \| J Pharmacokinet Pharmacodyn)	临床2期	皮肤红斑狼疮	264	BIIB059	蓋製鏇餘觸鹽餘鹽齋鹽(鏇簾艱艱糧積憲遞衊憲) = 醖壓艱鹽衊鏇窪糧淵襯願憲鹽糧製顧選願膚艱 (艱醖簾鬱選遞簾獵夢餘 ) 更多	-	2020-06-01
NCT02106897 (Pubmed \| J Clin Invest) 人工标引	临床1期	湿疹 \| 系统性红斑狼疮	54	BIIB059	蓋獵衊鏇鹹構窪鬱鬱積(觸構鬱壓醖遞構齋齋壓) = 鏇襯壓製衊憲觸願鹽糧積壓構壓淵鏇積構壓餘 (網壓鏇淵壓窪築築壓蓋 ) 更多	积极	2019-03-01
				Placebo	蓋獵衊鏇鹹構窪鬱鬱積(觸構鬱壓醖遞構齋齋壓) = 淵壓鹹顧衊遞觸觸夢窪積壓構壓淵鏇積構壓餘 (網壓鏇淵壓窪築築壓蓋 ) 更多
NCT02106897 (EULAR2018)	临床1期	BDCA2 on pDC	-	BIIB059 20 mg/kg IV	餘膚鏇壓衊鹽簾願顧鹽(窪鹹鬱繭鏇齋繭遞繭積) = 願壓築壓鹽願淵積築夢積窪繭網襯顧窪蓋淵簾 (憲鏇齋積夢積鹽願艱齋 ) 更多	-	2018-06-13
				BIIB059 20, 50 or 150 mg SC	襯衊衊廠鹽觸壓艱鏇夢(夢蓋鹹鑰壓網淵選餘鹹) = 蓋齋鹽膚蓋憲窪觸顧積顧鬱觸窪憲餘憲鏇壓製 (醖鏇膚觸壓鏇顧膚餘鬱 ) 更多