Bimekizumab

摘要：2023 年，美国 FDA 批准了 12 款治疗性抗体，涵盖多种疾病领域，展现了抗体药物研发的蓬勃发展。这些药物在结构设计和治疗机制上有诸多创新，为多种疾病的治疗带来了新希望。一、2023 年 FDA 批准治疗性抗体概况2023 年，FDA 共批准 55 种新分子实体，其中 12 款为治疗性抗体，另有 5 款非抗体蛋白药物，使蛋白药物占比达 31%。这 12 款抗体包括 8 款标准 IgG 格式、3 款二价双特异性抗体和 1 款三价双特异性抗体，无抗体 - 药物偶联物等其他类型。从作用靶点看，涉及 PD - 1、CD20 等多种靶点，覆盖阿尔茨海默病、淋巴瘤等多个疾病领域。[原文中图 1，展示 2023 年与往年 FDA 批准药物对比]二、阿尔茨海默病治疗新突破（一） Lecanemab：靶向淀粉样蛋白的创新药物Leqembi（lecanemab）是 2023 年批准的用于治疗阿尔茨海默病的重要药物。它是一种人源化 IgG1κ 抗体，源自鼠源抗体 hab158，能优先结合有毒的淀粉样蛋白寡聚体和原纤维，而非成熟斑块，这一特性使其在临床试验中表现出色。在随机双盲 3 期临床试验中，它能显著减缓患者认知能力下降，降低大脑淀粉样蛋白负荷和 tau 病理发展速度。不过，它在携带 APOE4 突变患者及部分女性患者中效果有限，且存在引发淀粉样蛋白相关成像异常的风险。[原文中图 4，展示淀粉样蛋白结构及相关抗体结合位点]三、淋巴瘤治疗的双特异性抗体新选择（一） Epcoritamab：CD20×CD3 双特异性抗体Epkinly（epcoritamab）是一种双特异性 “Duobody” 抗体，由 Abbvie 与 Genmab 合作开发。它通过结合 B 细胞上的 CD20 和 T 细胞上的 CD3，促进 T 细胞对 B 淋巴瘤细胞的杀伤。在治疗复发 / 难治性弥漫大 B 细胞淋巴瘤的临床试验中，客观缓解率达 61%，完全缓解率为 38%。其皮下给药方式具有便利性，不过存在细胞因子释放综合征等安全性问题。（二） Glofitamab：三价双特异性抗体的独特优势Columvi（glofitamab）是罗氏开发的三价双特异性抗体，采用 CrossMab 技术，具有两个 CD20 结合位点和一个 CD3 结合位点，增强了与 CD20 的结合亲和力。在临床试验中，它对复发 / 难治性弥漫大 B 细胞淋巴瘤表现出良好疗效，客观缓解率为 56%，完全缓解率达 43%。但细胞因子释放综合征发生率较高，需通过逐步递增剂量等方式管理安全性。[原文中图 3，展示 2023 年批准抗体的结构类型]四、多发性骨髓瘤治疗的新靶点与新策略（一） Talquetamab：靶向 GPRC5D 的双特异性抗体Talvey（talquetamab）是首个靶向 GPRC5D 的双特异性抗体，结合 CD3 和 GPRC5D，用于治疗多发性骨髓瘤。GPRC5D 是一种在骨髓瘤细胞上表达的 G 蛋白偶联受体，该抗体通过激活 T 细胞杀伤骨髓瘤细胞。临床试验显示，其客观缓解率达 74%，但存在细胞因子释放综合征和神经毒性等安全风险，需通过风险评估和缓解策略管理。（二） Elranatamab：BCMA×CD3 双特异性抗体的新进展Elrexfio（elranatamab）是靶向 BCMA 和 CD3 的双特异性抗体，BCMA 是治疗多发性骨髓瘤的成熟靶点。在临床试验中，它对复发 / 难治性多发性骨髓瘤的客观缓解率为 58%，完全缓解率为 26%。同样需要关注细胞因子释放综合征等安全性问题。[原文中表 4，展示多发性骨髓瘤治疗相关抗体]五、自身免疫性疾病与罕见病治疗的新进展（一） Bimekizumab：双靶向 IL - 17A/F 的银屑病治疗药物Bimzelx（bimekizumab）是一种人源化 IgG1κ 抗体，能同时结合 IL - 17A 和 IL - 17F，用于治疗中重度斑块状银屑病。IL - 17F 在银屑病病理中起重要作用，该抗体通过抑制这两种细胞因子发挥疗效。临床试验表明，它在改善银屑病症状方面优于对照药物，但存在一定感染风险。（二） Rozanolixizumab：靶向 FcRn 的重症肌无力治疗药物Rystiggo（rozanolixizumab）是一种人源化 IgG4κ 抗体，靶向新生儿 Fc 受体（FcRn），用于治疗全身性重症肌无力。它通过抑制 FcRn 对 IgG 的回收，降低致病性 IgG 水平。在临床试验中，它能显著降低患者体内致病性抗体水平，但可能增加感染风险，需注意监测。[原文中表 5，展示 FcRn 拮抗剂相关信息]六、其他重要治疗性抗体（一） Nirsevimab：长效预防呼吸道合胞病毒感染Beyfortus（nirsevimab）是一种人源化 IgG1κ 抗体，带有 YTE 突变，延长了半衰期，用于婴儿呼吸道合胞病毒（RSV）季节长周期预防。它靶向 RSV 的 F 蛋白，单次注射即可提供整个 RSV 季节的保护，在临床试验中显著降低 RSV 相关下呼吸道感染住院率。（二） Pozelimab：补体 C5 靶向治疗罕见病Veopoz（pozelimab）是一种人源 IgG4κ 抗体，靶向补体因子 C5，用于治疗罕见的 CHAPLE 病。它通过抑制 C5 的裂解，阻断补体系统过度激活，在临床试验中能快速使患者白蛋白水平正常化，但需注意感染风险，患者需在用药前接种脑膜炎球菌疫苗。七、总结与展望2023 年 FDA 批准的 12 款治疗性抗体在结构和机制上创新多样，双特异性抗体和长效抗体成为重要趋势，为多种疾病提供了更精准有效的治疗选择。尽管在安全性等方面仍有挑战，但这些药物的获批展现了抗体药物研发的活力，预计未来会有更多创新抗体药物问世，为患者带来新希望。识别微信二维码，添加抗体圈小编，符合条件者即可加入抗体圈微信群！请注明：姓名+研究方向！本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。

Pharmacokinetic and safety data from healthy volunteers anticipated around YE 2025 On track to initiate a Phase 2 study in 1H 2026 ORKA-002 preclinical data demonstrate the potential for dosing two to three times per year in psoriasis, a significant improvement over standard of care MENLO PARK, CA, USA I May 20, 2025 I Oruka Therapeutics, Inc. (“Oruka”) (Nasdaq: ORKA), a biotechnology company developing novel biologics designed to set a new standard for the treatment of chronic skin diseases including plaque psoriasis, today announced that it has initiated dosing of healthy volunteers in its first clinical trial of ORKA-002, the Company’s novel, subcutaneously administered, half-life extended monoclonal antibody targeting IL-17A and IL-17F (IL-17A/F). “With both ORKA-001 and ORKA-002 now in human trials, we are moving quickly to demonstrate the clinical differentiation of both assets,” said Lawrence Klein, PhD, Chief Executive Officer of Oruka. “Bimekizumab is launching extremely well as IL-17A/F has emerged as superior to IL-17A inhibition in several important indications. Uniquely, we could have the best targeting approaches for both IL-23p19 and IL-17A/F, potentially allowing us to offer the ideal regimen to patients through our ORKA-001 and -002 monotherapies and our ORKA-021 sequential combination.” The ORKA-002 Phase 1 trial is a double-blind, placebo-controlled, single ascending dose study evaluating the safety, tolerability and pharmacokinetics (PK) of ORKA-002 in approximately 24 healthy volunteers across three subcutaneous dose cohorts. Oruka expects to share interim data from this study around year end 2025. Pending data from the Phase 1 trial, Oruka plans to initiate a Phase 2 study of ORKA-002 in moderate-to-severe psoriasis in the first half of 2026. The planned study design will evaluate the safety and efficacy of multiple dose levels and regimens of ORKA-002, with a primary endpoint of PASI 100 at week 16. “ORKA-002 has the opportunity to become the best antibody in the IL-17 class, which is preferred when treating psoriasis with joint involvement or recalcitrant skin disease, as well as psoriatic arthritis, hidradenitis suppurativa, and beyond,” said Joana Goncalves, MBChB, Chief Medical Officer of Oruka. “With this program now in the clinic, we are one step closer to our goal of offering the most possible freedom from disease to patients with psoriasis and other conditions.” About ORKA-002 ORKA-002 is a novel, subcutaneously administered, half-life extended monoclonal antibody targeting IL-17A/F. Dual inhibition of both IL-17A and IL-17F has shown superior efficacy compared to IL-17A inhibition alone in psoriasis (PsO) and other indications, as shown by the performance of Bimzelx (bimekizumab) compared to Cosentyx (secukinumab) and Taltz (ixekizumab) in Phase 3 trials. These therapies all utilize monthly maintenance dosing in PsO and psoriatic arthritis (PsA), except Bimzelx in PsO patients weighing <120 kg, where Q8W maintenance dosing is recommended. In contrast, ORKA-002 has the potential to be dosed just two to three times per year in PsO and PsA, which we believe could allow ORKA-002 to become the leading therapy in the IL-17 class. Data from studies in non-human primates and other preclinical assays show that ORKA-002 binds to a similar epitope with similar affinity as bimekizumab and has a significantly extended half-life over three times longer than bimekizumab. About Oruka Therapeutics Oruka Therapeutics is developing novel biologics designed to set a new standard for the treatment of chronic skin diseases. Oruka’s mission is to offer patients suffering from chronic skin diseases like plaque psoriasis the greatest possible freedom from their condition by achieving high rates of complete disease clearance with dosing as infrequently as once or twice a year. Oruka is advancing a proprietary portfolio of potentially best-in-class antibodies that were engineered by Paragon Therapeutics and target the core mechanisms underlying plaque psoriasis and other dermatologic and inflammatory diseases. For more information, visit www.orukatx.com and follow Oruka on LinkedIn. SOURCE: Oruka Therapeutics