Linvoseltamab

3 月 10 日，辉瑞宣布，其 CD3/BCMA 双抗 Elranatamab（埃纳妥单抗）在国内获批上市，用于既往接受过至少三种治疗（含一种蛋白酶体抑制剂、一种免疫调节剂和一种抗 CD38 单克隆抗体）的复发或难治性多发性骨髓瘤成人患者的治疗。 截图来源：企业官微 新闻稿指出，该药在三种药物暴露后的复发或难治性多发性骨髓瘤（RRMM）患者中展现出了深度且持久的疗效，中位无进展生存期长达17.2个月，是目前同类产品中最长的，为复发或难治性多发性骨髓瘤患者带来了新的治疗希望。 Elranatamab 是一款靶向 CD3 × BCMA 的双抗，其对 BCMA 结合亲和力得到了优化提高。体外研究表明，生理水平的可溶性 APRIL 或 BAFF 不影响 Elranatamab 的药效。 2023 年 8 月，FDA 基于 MagnetisMM-3 研究的积极数据加速批准 Elranatamab 上市。MagnetisMM-3 是一项开放标签、多中心、非随机 II 期研究，旨在评估单药 Elranatamab 是否能为复发/难治性多发性骨髓瘤患者带来临床益处。主要研究终点是客观缓解率 (ORR) 和缓解持续时间 (DOR)。 数据显示，在接受推荐剂量的 97 名患者中，ORR 为 57.7% (95% CI：47.3%，67.7%)。获得缓解的患者中 90.4% 在 6 个月时维持缓解， 82.3% 在 9 个月时维持缓解。 在安全性方面，58% 的患者出现 CRS，59% 的患者出现神经毒性，3.3% 的患者出现 ICANS。0.5% 的患者出现 3 级 CRS，7% 的患者出现 3 级或 4 级神经毒性。最常见的不良反应（≥20%）为 CRS、疲劳、注射部位反应、腹泻、上呼吸道感染、肌肉骨骼疼痛、肺炎、食欲下降、皮疹、咳嗽、恶心和发热。 本次在国内获批上市，主要是基于一项 Ib/II 期的桥接试验（NCT05228470）的积极结果。ClinicalTrails 官网数据显示，Ib 期患者的 ORR 为 37.5%，II 期患者的 ORR 为 53.3%。 截图来源：Insight 数据库 Insight 数据库显示，全球共有 17 款 CD3/BCMA 双抗在研（仅统计活跃状态），仅强生特立妥单抗和辉瑞 Elranatamab 获批上市，再生元 Linvoseltamab 正处于上市申请阶段。 国产 CD3/BCMA 双抗共有 10 款在研，7 款进入临床阶段（包含批准临床）。其中康诺亚 CM336 和上海智翔 GR1803 进展最快，已启动 II 期临床。 值得一提的是，2024 年 11 月，康诺亚与 Platina Medicines Ltd（PML）就 CM336 达成独家许可协议，总金额达 6.26 亿美元。许可协议授予 PML 在全球（不包括中国内地、香港、澳门及台湾）开发、生产及商业化 CM336 的独家权利。 截图来源：Insight 数据库 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：ccai 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！

Regeneron Pharmaceuticals has received a positive opinion from the European Medicines Agency’s human medicines committee for the use of its investigational bispecific antibody linvoseltamab in multiple myeloma (MM). The Committee for Medicinal Products for Human Use (CHMP) has recommended that the drug be granted conditional marketing authorisation to treat relapsed and refractory MM in adults who have received at least three prior therapies, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody, and have also demonstrated disease progression on their last therapy. More than 35,000 new cases of MM, an incurable blood cancer that develops in plasma cells in the bone marrow, are diagnosed every year in Europe. While current MM treatments are able to slow its progression, most patients will ultimately experience relapse and require additional therapies. Linvoseltamab is designed to bridge B-cell maturation antigen on MM cells with CD3-expressing T cells to facilitate T-cell activation and cancer-cell killing. The CHMP’s decision on the drug was supported by positive results from the phase 1/2 LINKER-MM1 trial, which demonstrated a 71% objective response rate at a media follow-up of 14 months, with 50% of patients achieving a complete response (CR) or better and 63% achieving a very good partial response or better. The results presented at the European Hematology Association (EHA) Congress also showed a median duration of response (DoR) of 29 months for all linvoseltamab responders, while median DoR was not reached for those who achieved a CR or better. Median progression-free survival was not reached, and median overall survival of 31 months for all patients. Suzanne Lentzsch, director of the MM and amyloidosis programme at Columbia University, said at the time of the EHA presentation in June: “Previous results from LINKER-MM1 have demonstrated that linvoseltamab has compelling efficacy characterised by deep and durable responses… Additionally, a study using US-based electronic health record data to indirectly compare linvoseltamab to real-world standard-of-care treatment also supports the overall body of evidence for this investigational medicine in heavily pretreated MM. “Collectively, these presentations underscore the exciting potential of linvoseltamab as we await decisions from regulatory authorities.” The European Commission will now consider the CHMP’s recommendation as it makes a final decision on linvoseltamab, expected in the coming months.