Nipocalimab-aahu

点击蓝字 关注我们 本 期 看 点 重症肌无力（gMG）是一种典型的抗体介导型神经—肌肉接头疾病，全球约 70 万患者，美国约 10 万人，每年新诊断病例中仍有 10–15% 为青少年患者。过去十年，这一罕见病领域却经历了罕见的“技术爆发期”：从补体 C5 抑制，到 FcRn 阻断，再到如今直接靶向 B 细胞本身，gMG 正的治疗手段不断推陈出新。 本期内容 01 安进丨CD19靶向单抗Uplizna 02 C5补体抑制剂 03 04 FcRn靶点 总结与展望 【01 安进丨CD19靶向单抗Uplizna】 自2021年底以来，全球重症肌无力（gMG）靶向治疗领域迎来多款新药获批。在此背景下，安进公司于2025年12月11日宣布，其CD19靶向单抗Uplizna（inebilizumab）正式获得美国FDA批准，用于治疗抗AChR抗体阳性及抗MuSK抗体阳性的成人gMG患者。 Uplizna的突出优势在于其每年仅需给药两次的便利性，这在当前gMG治疗市场中具有显著差异化竞争力。临床III期MINT试验数据显示，治疗26周后，Uplizna组患者MG-ADL评分改善较安慰剂组高出1.9分，并在AChR阳性亚组中显示疗效可持续至52周。同时，该药还表现出良好的激素减量潜力，第26周时87.4%的Uplizna组患者将日激素用量降至5mg以下。 目前gMG市场已形成C5抑制剂、FcRn阻断剂与B细胞靶向疗法三足鼎立的竞争格局。 除Uplizna外，市场主要参与者还包括Argenx的Vyvgart、强生的Imaavy、UCB的Rystiggo与Zilbrysq，以及阿斯利康的Soliris和Ultomiris。花旗分析指出，Uplizna凭借其独特作用机制、给药便利性和激素减量潜力，有望在2030年前实现17亿美元的gMG领域销售额。 【02 C5补体抑制剂】 2025年10月11日，优时比（UCB）宣布：泽卢克布仑钠（zilucoplan，商品名海外为 ZILBRYSQ）获国家药监局批准，在与常规治疗联合时用于AChR抗体阳性的成人全身型重症肌无力（gMG）。它是全球首个且唯一可皮下注射、自行给药的C5抑制剂，有望显著降低就医负担、提升依从性与生活质量。 重症肌无力是一种罕见的自身免疫性神经肌肉疾病，患者常出现言语、吞咽、呼吸和肢体肌力障碍，长期依赖静脉输注治疗。以往的C5抑制剂（如依库珠单抗、瑞利珠单抗）需定期前往医院输液，既耗时又增加感染风险。泽卢克布仑钠的出现，首次让患者可在经过培训后于家中完成注射，从而显著减轻就医负担，标志着重症肌无力从“院内管理”走向“居家管理”的新阶段。 Gefurulimab丨双特异性C5抗体 2025年7月24日，阿斯利康欣然宣布， 其自主研发的gefurulimab（ALXN1720）在PREVAIL III期试验中取得主要终点成功。gefurulimab为一款约25 kDa的双特异性纳米抗体，能够有效结合抗C5可变区与白蛋白结合片段，为皮下注射剂型，给药周期为每周一次； 数据显示，与安慰剂相比，gefurulimab在第26周时，在重症肌无力日常生活活动能力量表（MG-ADL）总分上显示出具有统计学显著性和临床意义的、相较于基线的改善。 后续计划向FDA、EMA及NMPA提交注册申请，预计2026年实现全球上市。 上述产品为2020年阿斯利康斥资约390亿美元，收购Alexion公司所得，Alexion作为C5补体抑制的先锋，既往已经推动2款C5补体抑制剂上市。 依库珠单抗（Soliris®，eculizumab） 依库珠单抗（Soliris®）是一种人源化IgG2/4κ单克隆抗体。在阵发性睡眠性血红蛋白尿(PNH）患者中，可持续防止溶血、减少输血需求；在非典型溶血尿毒综合征(aHUS)中，则有效预防微血管病变；在gMG和抗体阳性的成年患者的视神经脊髓炎症（NMOSD）等适应症中，也展现出良好疗效。 2007年3月，Soliris®获FDA批准用于PNH，开启C5抑制疗法新时代； 2018年，Soliris®在中国获批，用于PNH和非典型溶血性尿毒症综合征（aHUS）； 2023年6月13日，NMPA批准Soliris®（商品名舒立瑞）用于抗AChR抗体阳性成人全身型重症肌无力（gMG）； 2023年11月，通过国家医保谈判；2024年1月1日，新价格正式执行，按乙类医保70%报销计算，显著减轻了长期用药经济压力。 瑞利珠单抗（Ultomiris®，ravulizumab） 2025年4月22日，中国上海—— 长效C5补体抑制剂伟立瑞®（英文商品名：Ultomiris®，通用名：瑞利珠单抗注射液）在中国正式获批与常规治疗药物联合用于治疗抗乙酰胆碱受体（AChR）抗体阳性的成人全身型重症肌无力（gMG）患者。 与此同时，FcRn靶点也成为当代的热门赛道。 03 FcRn靶点 FcRn（新生儿Fc受体）是一种“重复利用”IgG的运输通道，广泛分布于血管内皮、胎盘、肠道上皮和乳腺等处。  FcRn及其配体的结构  FcRn对IgG的转运保护机制 其简化作用机制如下： 捕获回收：血管内皮细胞会吞噬血液中的蛋白质，FcRn在细胞内的低pH环境下与IgG的Fc段紧密结合，避免IgG被送入溶酶体降解； 再循环：结合后的IgG被运回细胞表面，以中性pH释放回血液，从而延长了IgG在体内的半衰期； 阻断应用：在自身免疫病中，病理性IgG水平过高，通过抗体药物阻断FcRn–IgG结合，可加速这些自身抗体的清除（可下降45%–85%），同时不影响IgM、IgA和白蛋白；停药后IgG水平可在约60天内恢复。 这种有选择且可逆的清除机制，使FcRn成为治疗多种IgG介导自身免疫病的理想靶点。 国内产品上市进度 强生尼卡利单抗 •  2025年4月23日，CDE官网公示，强生尼卡利单抗注射液在中国申报上市，此前该药已被纳入优先审评，适用于治疗自身抗体阳性的全身型重症肌无力（gMG）成人患者和青少年患者（大于12岁）。 •  尼卡利单抗是强生通过约65亿美元收购Momenta Pharmaceuticals获得的在研FcRn抗体。2024年8月，该药已在美国申报上市，用于重症肌无力。 优时比罗泽利昔单抗 •  2025年3月31日，药监局官网显示，优时比FcRn单抗罗泽利昔单抗注射液获批上市。根据公开资料及既往临床研究，Insight数据库推测该适应症为重症肌无力（gMG）。 巴托利单抗 •  和铂医药与石药集团引进的巴托利单抗也已于2024年7月申报上市并获受理。但海外合作公司却放弃了这个产品。 在全球FcRn靶点竞争上，强生、优时比等企业已经在技术迭代。而Immunovant暂不提交巴托利单抗上市申请的决定，凸显了FcRn抑制剂赛道的激烈竞争，也揭示了跨国药企与本土玩家在全球权益布局中的深层博弈。 04  总结与展望 回望gMG治疗领域的技术发展路径，治疗靶点正不断向疾病源头推进：C5抑制剂作用于补体终端，阻断免疫破坏效应；FcRn阻断剂旨在加速抗体清除，降低循环中的抗体负荷；而Uplizna所代表的CD19 B细胞靶向疗法，则进一步溯源至产生致病抗体的B细胞本身，直指自身免疫反应的起源。 这并非单纯的技术迭代，而更可能形成一种互补与共存的未来格局。针对急性发作控制、长期病情维持、激素减量需求及治疗依从性管理等不同临床目标，不同机制的药物将各展所长。对产业而言，gMG市场已逐渐超越对“重磅单品”的依赖，演进为一个能够容纳多技术路线并行、差异化临床定位与长期疾病管理模式的细分赛道。 随着给药频率从每周一次向半年一次演进，治疗场景也从医院向家庭延伸，gMG的治疗正从单一的疾病管理，转变为对疾病机制理解深度、临床开发策略与商业化综合能力的系统性考验。下一阶段的竞争，将不只体现在疗效数据上，更取决于对疾病生物学更深刻的理解与转化能力。 ★

Since late 2021, a bevy of targeted generalized myasthenia gravis therapies has crossed the regulatory finish line in the U.S., beginning with argenx’s FcRn blocker Vyvgart four years ago and most recently culminating in April’s approval of Johnson & Johnson’s Imaavy. Amid a swell of regulatory successes in the myasthenia gravis arena this decade, Amgen is wading into the fray with a new indication for its monoclonal antibody Uplizna.Thursday, the FDA greenlighted Uplizna (inebilizumab) to treat generalized myasthenia gravis (gMG) in adults who are anti-acetylcholine receptor (AChR) and anti-muscle specific tyrosine kinase (MuSK) antibody positive. After two loading doses, Uplizna for gMG is administered just twice a year, Amgen noted in a Dec. 11 press release.Myasthenia gravis is a rare autoimmune disorder that hampers neuromuscular communication, which can in turn cause fluctuating muscle weakness, Amgen explained. The condition—which is estimated to affect about 80,000 to 100,000 people in the U.S. by Amgen’s reckoning—is thought to be primarily driven by AChR and MuSK autoantibodies, which are produced by CD19+B cells, the company added.Since late 2021, a bevy of targeted gMG therapies has crossed the regulatory finish line in the U.S. and beyond, beginning with argenx’s FcRn blocker Vyvgart (efgartigimod) four years ago and most recently culminating in April’s approval of Johnson & Johnson’s Imaavy (nipocalimab), prior to the Uplizna nod."This approval marks a significant advancement for people living with gMG," Jay Bradner, M.D., Amgen’s executive vice president of R&D, said in a statement."By selectively targeting CD19-positive B cells, Uplizna offers a new approach to treatment that addresses a biological root cause of disease,” he continued. “Uplizna is conveniently dosed twice a year and delivers durable efficacy, helping people manage debilitating symptoms that can compromise daily function – including trouble breathing, speaking and seeing." Uplizna’s efficacy in gMG is thought to lie in its “targeted and sustained” depletion of cells essential to the underlying disease process, which Amgen defined in its release as autoantibody-producing CD19+ B cells, including plasmablasts and some plasma cells.The FDA gave Uplizna the thumbs-up after reviewing data from Amgen’s phase 3 Mint trial. At the study’s 26-week mark, treatment with Uplizna was associated with a 1.9-point difference on the Myasthenia Gravis Activities of Daily Living (MG-ADL) scale—a common measure of myasthenia gravis symptoms—versus placebo, Amgen noted in its release. Specifically, Uplizna led to a 4.2-point reduction on the scale versus a 2.2-point reduction in the trial’s control cohort.The drug’s benefits persisted through an entire year in the trial among patients in the AChR-positive subgroup, Amgen pointed out.The California pharma also touted a steroid taper baked into the study’s protocol, noting that by Week 26, 87.4% of patients on Uplizna and 84.6% of those on placebo had curbed their steroid dose to 5 mg or less per day.The approval marks Uplizna’s second this year and third overall. Back in April, the antibody drug was cleared by the FDA to treat adults with immunoglobulin G4-related disease, building on the drug’s original 2020 green light to treat certain neuromyelitis optica spectrum disorder patients.Uplizna is entering the gMG market at a busy time. Aside from argenx’s Vyvgart and J&J’s Imaavy, UCB’s Rystiggo and Zilbrysq and AstraZeneca and Alexion’s Soliris and Ultomiris also carry recent approvals in the indication. Meanwhile, argenx scored a thumbs-up for a subcutaneous version of its drug, dubbed Vyvgart Hytrulo, back in 2023.In terms of competitive advantages, Amgen appears to be leaning heavily on the potential convenience edge that Uplizna’s twice-a-year dosing could provide. The treatment schedules for the other targeted gMG therapies on the market tend to require maintenance dosing every few weeks, with the timing sometimes dependent on factors related to each patient.Moreover, analysts at Citi Research noted on Thursday that Uplizna's CD-19 targeting mechanism, coupled with its efficacy across gMG subgroups, dosing convenience and steroid-sparing potential, could present "unique differentiation" in the crowded market. Uplizna could be looking at a $1.7 billion sales opportunity in gMG by 2030, the Citi team added. With the approval of Imaavy in April, meanwhile, J&J asserted that its label covered the “broadest population of people living with gMG,” banking those claims in large part on the fact that its drug is approved not only in adults but in people ages 12 and up.Elsewhere, argenx recently scored an FDA nod for a prefilled syringe format of Vyvgart Hytrulo that can be administered at home. And the company is homing in on a potential approval in seronegative patients, which describes the minority of people with gMG who lack detectable AChR or MuSK antibodies in their blood, making the already rare autoimmune condition even trickier to diagnose.Editor's note: This story has been updated with commentary from a Dec. 11 analyst note.