Sibeprenlimab

点击蓝字关注我们本周，热点不少。首先看审评审批方面，非常值得关注的就是，罗氏多发性硬化症重磅药物奥瑞利珠单抗国内获批上市，成为国内第二款获批上市的FcRn单抗；其次是研发方面，值得一提的是，复宏汉霖贝伐珠单抗眼科Ⅲ期研究成功；再次是交易及投融资方面，和誉医药匹米替尼全球权益落地；最后是其他方面，2024年全球畅销药TOP100公布，K药以294.82亿美元排名第一。本周盘点包括审评审批、研发、交易及投融资以及其他四大板块，统计时间为2025.3.31-4.3，包含24条信息。 审评审批NMPA上市批准1、3月31日，NMPA官网显示，罗氏的奥瑞利珠单抗（Ocrelizumab、商品名：OCREVUS）获批上市，每六个月静脉输注一次给药，用于治疗成人复发型多发性硬化症（RMS，包括临床孤立综合征、复发缓解型多发性硬化和活动性继发进展型多发性硬化）和成人原发进展型多发性硬化症（PPMS）。奥瑞利珠单抗是一种靶向CD20-阳性B细胞的人源化单克隆抗体。2、3月31日，NMPA官网显示，百时美施贵宝的纳武利尤单抗与伊匹木单抗联合疗法获批新适应症，用于不可切除或晚期肝细胞癌(HCC)成人患者的一线治疗，成为中国首个且目前唯一获批的肝细胞癌一线双免疫联合疗法。纳武利尤单抗是全球首个获批的PD-1抑制剂，伊匹木单抗是一种细胞毒性T淋巴细胞抗原-4（CTLA-4）抑制剂。3、3月31日，NMPA官网显示，优时比的罗泽利昔珠单抗获批上市，预测用于治疗重症肌无力（gMG）。该药是一款靶向FcRn的单抗，最早于2023年6月在美国获批，优时比还在开发罗泽利昔珠单抗对于纤维肌痛、MOG抗体相关疾病等适应症的应用潜力。 国内已有一款FcRn单抗获批上市，即再鼎医药的艾加莫德α。石药基团的巴托利单抗已申报上市，正在审评中。4、3月31日，NMPA官网显示，参天公司5.1类化药他氟噻吗滴眼液获批上市，适应症为降低开角型青光眼或高眼压症患者的眼压，用于对局部单独使用β-受体阻滞剂或前列腺素衍生物疗效不佳而需要联合治疗，以及对使用无防腐剂滴眼液可能获益的患者。他氟噻吗滴眼液是一款含有青光眼一线治疗药物前列腺素（PG）衍生物，同时不含防腐剂的眼用复方制剂。5、3月31日，NMPA官网显示，恒瑞医药的硫酸艾玛昔替尼（SHR0302片）新适应症获批，用于治疗对一种或多种传统合成改善病情抗风湿药（csDMARDs）疗效不佳或不耐受的成人中重度活动性类风湿关节炎患者。艾玛昔替尼是恒瑞医药自主研发的高选择性的JAK1抑制剂，首次在中国获批上市，用于治疗活动性强直性脊柱炎成人患者。申请6、4月1日，CDE官网显示，永泰生物1类新药爱可仑赛注射液递交附条件新药上市申请，这是永泰生物在研的广谱性的细胞免疫治疗产品（EAL），于2025年3月正式被CDE纳入优先审评，拟定适应症为：原发性肝细胞癌根治术后高复发风险的部分人群［免疫特性人群：患者需满足以下标准中的至少两项：无微血管侵犯；术后中性粒细胞和淋巴细胞比值（NLR）＜3；术后血小板和淋巴细胞比值（PLR）＜110］术后预防复发治疗。7、4月1日，CDE官网显示，华东医药的司美格鲁肽注射液生物类似药（研发代码：HDG1901）申报上市，用于成人2型糖尿病患者的血糖控制。司美格鲁肽注射液是一种长效胰高血糖素样肽-1（GLP-1）受体激动剂，与人GLP-1有94%的序列同源性。原研产品由诺和诺德（Novo Nordisk）研发（商品名：诺和泰），已经在全球范围内获批用于2型糖尿病患者的血糖控制、肥胖或超重患者的长期体重管理、降低心血管事件风险等适应症。8、4月3日，CDE官网显示，第一三共的注射用德曲妥珠单抗新适应症申报上市。德曲妥珠单抗（商品名：Enhertu）是一款靶向HER2的抗体偶联药物（ADC），由阿斯利康和第一三共联合开发，此前已经在中国获批4项适应症。 德曲妥珠单抗治疗HER2表达实体瘤适应症正在中国处于上市申报阶段，这是一类“不限癌种”的适应症。9、4月3日，CDE官网显示，默沙东的Clesrovimab注射液申报上市，预测适应症为：用于即将进入或出生在第一个呼吸道合胞病毒（RSV）流行季的新生儿和婴儿预防RSV所致的下呼吸道感染。Clesrovimab（MK-1654）是一种在研的半衰期延长的单克隆抗体，可作为被动免疫手段，用于预防RSV疾病。10、4月3日，CDE官网显示，阿斯利康的本瑞利珠单抗注射液新适应症申报上市。本瑞利珠单抗（Benralizumab）是阿斯利康开发的一款靶向IL-5受体的单克隆抗体，此前已经在中国获批用于成人和12岁及以上青少年重度嗜酸粒细胞性哮喘的维持治疗。在美国，该产品还已经获FDA批准用于治疗嗜酸性肉芽肿性多血管炎（EGPA）的成年患者。临床批准       11、3月31日，CDE官网显示，中美瑞康（Ractigen Therapeutics）的RAG-1C获批临床，用于治疗增殖性玻璃体视网膜病变（PVR）。RAG-1C是中美瑞康第二款进入临床的saRNA药物。此前，该公司的首款saRNA药物RAG-01已获得美国FDA的IND许可，并在澳大利亚开展的Ⅰ期临床试验中获得了积极的初步疗效和安全性数据。12、4月1日，CDE官网显示，恒瑞医药1类新药HRS-6719片获批临床，拟开发治疗甲硫腺苷磷酸化酶（MTAP）缺失的实体瘤。本次为该产品首次在中国获批临床。PRMT5是MTAP突变的“合成致死”靶点。全球范围内已有数十款PRMT5抑制剂进入临床开发阶段，进展较快的产品已经进入Ⅱ期临床阶段。13、4月1日，CDE官网显示，海博为药业1类新药HBW-012336胶囊获批临床，拟开发治疗携带KRAS G12D突变的局部晚期或转移性实体瘤。这是一款KRAS G12D抑制剂。本次为该产品首次在中国获批临床。 除了对KRAS G12D 抑制剂的开发，海博为药业还布局了口服Pan-KRAS抑制剂研发管线，已筛选出具有显著开发潜力的候选化合物HBW-016-K。14、4月2日，CDE官网显示，长春高新1类新药GenSci128片获批临床，拟开发治疗携带TP53 Y220C突变的局部晚期或转移性实体瘤。这是一款是针对TP53 Y220C突变的选择性重激活剂。本次为该产品首次在中国获批IND。15、4月2日，CDE官网显示，阿斯利康1类新药AZD5492获批两项临床，拟用于治疗系统性红斑狼疮、特发性炎症性肌病。这是一款CD20×TCR×CD8三特异性抗体，是由CD8引导的T细胞衔接器（TCE）。该产品最早于2024年10月在中国获批临床，适应症为复发性或难治性B细胞恶性肿瘤。16、4月3日，CDE官网显示，三生国健1类新药SSGJ-627注射液获批临床，拟开发治疗溃疡性结肠炎（UC）。这是一款抗TL1A单抗。本次是该产品首次在中国获批临床。SSGJ-627是三生国健研发的重组抗TL1A人源化单克隆抗体。FDA上市批准17、4月3日，FDA官网显示，诺华的阿曲生坦（Atrasentan、商品名：Vanrafia）获加速批准，用于降低有疾病进展风险的原发性免疫球蛋白A肾病（IgAN）成人患者的蛋白尿。阿曲生坦成为了首个获批用于减少原发性IgA肾病蛋白尿的选择性ETA拮抗剂。2023年，诺华以35亿美元收购了Chinook，获得了atrasentan和APRIL单抗zigakibart两款IgA肾病药物。申请18、3月31日，FDA官网显示，大冢制药的Sibeprenlimab递交生物制品许可申请（BLA），用于治疗免疫球蛋白A肾病（IgAN）。Sibeprenlimab是Visterra开发的一款靶向抑制增殖诱导配体（APRIL）的单抗。目前，全球仅Nefecon（16mg、每日1次）、Sparsentan（片剂、200/400mg、每日1次）和伊普可泮（胶囊、200mg、每日2次）三款药物获批用于治疗IgAN。EMA上市批准19、4月1日，EMA官网显示，辉瑞的二价呼吸道合胞病毒（RSV）疫苗（商品名：Abrysvo）新适应症获批，扩展至预防18至59岁人群由RSV引起的下呼吸道疾病（LRTD），进一步扩大了原有针对60岁及以上人群的适应症，使Abrysvo成为欧盟目前覆盖范围最广的RSV疫苗，Abrysvo是一种无佐剂二价疫苗，旨在预防RSV-A和RSV-B亚群引起的下呼吸道疾病。研发临床状态20、3月31日，药物临床试验登记与信息公示平台显示，恒瑞医药启动了GLP-1受体激动剂HRS-7535片用于超重或肥胖受试者的Ⅲ期临床研究。2024年5月，恒瑞将包括HRS-7535在内的GLP-1产品组合以NewCo的形式授权出海，获得了首付款和近期里程碑总计1.1亿美元，累计不超过59.25亿美元的的临床开发、监管和销售里程碑款，Hercules19.9%的股权。临床数据21、4月2日，罗氏公布了奥瑞利珠单抗治疗复发性多发性硬化症（RMS）的Ⅲ期MUSETTE结果，显示未达到主要终点。该研究是一项多中心、随机、双盲、阳性药物对照临床试验（n=864），评估了高剂量奥瑞利珠单抗（1200mg或1800mg，静脉注射，每24周1次）对比已获批剂量奥瑞利珠单抗（600mg，静脉注射，每24周1次）治疗RMS成人患者的有效性、安全性和药代动力学（PK）。该药是罗氏与渤健合作开发的一款靶向CD20阳性B细胞的人源化单抗。22、4月2日，复宏汉霖公布了HLX04-O治疗湿性年龄相关性黄斑变性（wAMD）中国患者的Ⅲ期HLX04-O-wAMD-CN研究结果，已达到预设主要研究终点。该研究为一项多中心、随机、双盲、阳性对照的非劣效Ⅲ期临床试验（n=388），旨在评估玻璃体内注射（IVT）HLX04-O（1.25mg，每4周1次）或雷珠单抗（0.5mg，每4周1次）治疗wAMD患者的有效性和安全性。HLX04-O是复宏汉霖利用基因工程技术构建的一款重组抗血管内皮生长因子（VEGF）人源化单抗。交易及投融资23、4月1日，和誉医药宣布，与默克签订授权协议，行使匹米替尼全球商业化选择权，行权费用为8500万美元。2023年12月，和誉医药与默克就CSF-1R抑制剂匹米替尼订立协议。默克最初获得匹米替尼在中国内地、中国香港、中国澳门及中国台湾所有适应症进行商业化的独家授权，并拥有全球商业化权利的独家选择权。匹米替尼是由和誉医药独立研发的一种新型、口服、高选择性且高效的小分子CSF-1R抑制剂。其他24、2024年，2024年全球销售额超过10亿美元的药物约169款，TOP100药品的上榜门槛是17.66亿美元（折合人民币约125.77亿元），合计销售总收入为5049.17亿美元。2024年，K药以294.82亿美元排名第一，GLP-1巨头司美格鲁肽三款产品Wegovy/Ozempic/Rybelsus合计创收292.96亿美元排名第二。END2025金笔奖征文活动开启，来投稿吧！领取CPHI & PMEC China 2025展会门票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~

PRINCETON, NJ, USA & TOKYO, Japan I March 31, 2025 I Otsuka Pharmaceutical Development & Commercialization, Inc. and Otsuka Pharmaceutical Co., Ltd. (Otsuka) today announce the filing of a Biologics License Application (BLA) with the U.S. Food and Drug Administration (FDA) for sibeprenlimab, an investigational monoclonal antibody that selectively inhibits the activity of APRIL ( A PR oliferation- I nducing L igand) in adults with immunoglobulin A nephropathy (IgAN). APRIL plays a key role in the 4-hit process of IgAN pathogenesis and is an important initiating and sustaining factor in IgAN progression by promoting the production of pathogenic Gd-IgA1 and immune complex formation. Sibeprenlimab is a single-dose prefilled syringe for subcutaneous injection every four weeks intended for self-administration or administration by caregiver, providing patients the option of convenience at home. IgAN is a progressive, autoimmune, chronic kidney disease that is associated with a high risk for progression to end-stage kidney disease (ESKD) over the lifetime of many patients. 1 In 2024, the FDA granted a Breakthrough Therapy designation for sibeprenlimab following favorable results of the Phase 2 ENVISION clinical trial. 2 This designation accelerates the development and regulatory review of potential new medicines intended to treat a serious condition and address a significant unmet medical need. If approved, sibeprenlimab would be administered via injection every four weeks, which would allow patients the convenience and option of self-administration in the home setting. 3 The BLA submission, Otsuka’s first, is supported by results from the Phase 2 ENVISION clinical trial (NCT04287985) and the Phase 3 VISIONARY clinical trial (NCT05248646), which met its primary endpoint by demonstrating that sibeprenlimab produced a statistically significant and clinically meaningful reduction in 24-hour uPCR (urine protein-to-creatine ratio) compared to placebo after nine months of treatment. 4 In the trial, the safety profile of sibeprenlimab was favorable and consistent with previously reported data. “This BLA filing marks an important milestone in Otsuka’s commitment to address unmet needs in kidney diseases,” said John Kraus, M.D., Ph.D., executive vice president and chief medical officer, Otsuka Pharmaceutical Development & Commercialization, Inc. “Sibeprenlimab’s unique mechanism of action inhibits the activity of APRIL and addresses an IgA-specific driver of kidney loss in IgA nephropathy. APRIL is a cytokine that plays a key role in the pathogenesis of IgA nephropathy and we are optimistic about its potential to be an important treatment option for this progressive kidney disease. On behalf of Otsuka, we are grateful to every patient, caregiver and healthcare professional who has contributed so much to advancing this important research.” The VISIONARY study is a multicenter, randomized, double-blind, placebo-controlled trial consisting of approximately 530 adult patients (largest trial to date) with IgA nephropathy who were receiving standard-of-care therapy (defined as maximally tolerated ACE inhibitor or ARB +/- SGLT2 inhibitor), designed to evaluate the efficacy and safety of sibeprenlimab 400 mg administered subcutaneously every four weeks, compared to placebo. The primary efficacy endpoint is to evaluate the change in 24-hour uPCR at 9 months compared with baseline. 4 The secondary endpoint is to evaluate the annualized slope of eGFR estimated over ~24 months. 4 “This BLA for sibeprenlimab represents a significant achievement in our journey to bring innovative treatments to patients with IgA nephropathy,” commented Brian Pereira, M.D., CEO of Visterra, Inc., the U.S. affiliate of Otsuka that designed and engineered sibeprenlimab. “We look forward to the FDA’s review and are grateful for the opportunity to help develop a treatment that could alter the course of this challenging kidney disease and improve patient outcomes.” About Sibeprenlimab Sibeprenlimab (formerly VIS649) was designed and engineered by Visterra, Inc., a wholly owned subsidiary of Otsuka. Pre-clinical and early-stage trials of sibeprenlimab were also conducted by Visterra. Sibeprenlimab is an investigational monoclonal antibody that selectively binds to and inhibits the activity of APRIL and plays a key role in the 4-hit process. By binding and inhibiting APRIL, sibeprenlimab may help reduce the amount of immunoglobulin A (IgA) and Gd-IgA1 levels. Lower levels of Gd-IgA1 provide less substrate for immune complex formation, and may also result in reduced auto-antibody production. Decreased immune complex creation should result in diminished deposition in the kidney, and reduced proteinuria and kidney inflammation. By reducing the production of Gd-IgA1, sibeprenlimab may help slow kidney damage and progression toward ESKD. 2,4,5,6 By inhibiting APRIL, sibeprenlimab may help address one of the IgA nephropathy-specific drivers for nephron loss. About Immunoglobulin A Nephropathy and APRIL IgA nephropathy is a progressive, autoimmune, chronic kidney disease that typically manifests in adults aged 20-40 years and leads to ESKD over the lifetime of most patients. 1,7,8 IgA nephropathy is characterized by the accumulation of Gd-IgA1 complexes in the kidneys. IgA nephropathy can lead to progressive loss of kidney function and, eventually, ESKD, imposing a significant burden on patients. 7 Despite supportive care, there is an unmet need for treatments that address the root cause of the condition. Continued research in the disease remains crucial to uncovering opportunities for advancement in our understanding and treatment of patients. 9 APRIL, a cytokine in the tumor necrosis factor (TNF) family, is integral to the pathogenesis and progression of IgA nephropathy. It promotes the survival and class switching of B cells to produce IgA, particularly the pathogenic galactose-deficient IgA1 (Gd-IgA1) that forms immune complexes in the kidneys. 9 About Otsuka Otsuka Pharmaceutical Co., Ltd. is a global healthcare company with the corporate philosophy: Otsuka–people creating new products for better health worldwide . Otsuka researches, develops, manufactures, and markets innovative products, with a focus on pharmaceutical products to meet unmet medical needs and nutraceutical products for the maintenance of everyday health. In pharmaceuticals, Otsuka is a leader in the challenging areas of mental, renal, and cardiovascular health and has additional research programs in oncology and on several under-addressed diseases including tuberculosis, a significant global public health issue. These commitments illustrate how Otsuka is a “big venture” company at heart, applying a youthful spirit of creativity in everything it does. Otsuka established a presence in the U.S. in 1973 and today its U.S. affiliates include Otsuka Pharmaceutical Development & Commercialization, Inc. (OPDC) and Otsuka America Pharmaceutical, Inc. (OAPI). These two companies’ 2,250 employees in the U.S. develop and commercialize medicines in the areas of mental health and nephrology, using cutting-edge technology to address unmet healthcare needs. OPDC and OAPI are indirect subsidiaries of Otsuka Pharmaceutical Co., Ltd., which is a subsidiary of Otsuka Holdings Co., Ltd. headquartered in Tokyo, Japan. The Otsuka group of companies employed 35,340 people worldwide and had consolidated sales of approximately USD 14.7 billion in 2024. All Otsuka stories start by taking the road less traveled. Learn more about Otsuka in the U.S. at www.otsuka-us.com and connect with us on LinkedIn and Twitter at @OtsukaUS . Otsuka Pharmaceutical Co., Ltd.’s global website is accessible at https://www.otsuka.co.jp/en/. About Visterra Visterra is a biologics research and early-stage clinical development biotechnology company and a wholly owned subsidiary of Otsuka America, Inc. committed to developing innovative antibody-based therapies for the treatment of patients with immune-mediated kidney diseases and other hard-to-treat diseases. Its proprietary Hierotope® platform enables the design and engineering of precision biologics-based product candidates that specifically bind to, and modulate, key disease targets that are not adequately addressed by traditional therapeutic approaches. The platform also includes Fc engineering capabilities for half-life extension, bispecific antibodies and antibody-drug conjugates (ADCs). Visterra’s pipeline includes programs targeting kidney diseases, immunologically-driven diseases and infectious diseases. For more information, visit www.visterrainc.com . SOURCE: Otsuka Pharmaceutical