Sibeprenlimab

PRINCETON, NJ, USA & TOKYO, Japan I May 27, 2025 I Otsuka Pharmaceutical Development & Commercialization, Inc. and Otsuka Pharmaceutical Co., Ltd. (Otsuka) today announce the U.S. Food and Drug Administration (FDA) has accepted for review the Biologics License Application (BLA) 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 pathogenesis of IgAN as explained by the 4-hit process, in which pathogenic galactose-deficient IgA (Gd-IgA1) is produced, leading to the synthesis of autoantibodies against Gd-IgA1, immune complex formation, and deposition in the glomerular mesangium. Sibeprenlimab is a single-dose prefilled syringe for subcutaneous injection every four weeks intended for self-administration, providing patients the convenience of at-home delivery. The BLA is supported by the Phase 3 VISIONARY clinical trial (NCT05248646), which met its primary endpoint at the prespecified interim analysis, and results from the Phase 2 ENVISION clinical trial (NCT04287985). Sibeprenlimab demonstrated a statistically significant and clinically meaningful reduction in 24-hour uPCR after nine months of treatment compared to placebo in the Phase 3 VISIONARY trial. 1 The BLA has been granted priority review and a Prescription Drug User Fee Act (PDUFA) target action date of November 28, 2025. “Over the past decade, Otsuka has consistently approached difficult-to-treat diseases in nephrology with scientific and clinical innovation, seeking to provide crucial advancements for underserved patients with complex conditions like IgA nephropathy,” said John Kraus, M.D., Ph.D., executive vice president and chief medical officer, Otsuka Pharmaceutical Development & Commercialization, Inc. “If approved, sibeprenlimab would enable individuals living with IgA nephropathy to self-inject once every 4 weeks. We are thankful to share a potential treatment that could offer important clinical benefits and convenience to those living with this disease.” Sibeprenlimab has Breakthrough Therapy designation for the treatment of IgAN based on the favorable results from the Phase 2 (ENVISION) trial (NCT04287985). 2 IgAN is a progressive, autoimmune, chronic kidney disease that can lead to end-stage kidney disease (ESKD) over the lifetime of most patients under current optimized standard care. 3 Targeting APRIL represents a potential therapeutic strategy to disrupt IgAN’s pathogenesis via the 4-hit process, which may reduce production of immune complexes, which can deposit into kidney tissue, and may lead to ESKD and the need for transplantation. 1,2,4,5 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 IgAN-specific drivers for nephron loss. About IgAN and APRIL IgAN 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. 3,6,7 IgAN is characterized by the accumulation of Gd-IgA1 complexes in the kidneys. IgAN can lead to progressive loss of kidney function and, eventually, ESKD, imposing a significant burden on patients. 6 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. 8 APRIL, a cytokine in the tumor necrosis factor (TNF) family, is integral to the pathogenesis and progression of IgAN. It promotes the survival and class switching of B cells to produce IgA, particularly the pathogenic Gd-IgA1 that forms immune complexes in the kidneys. 8 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/. References SOURCE: Otsuka Pharmaceutical Co

FDA授予突破性单抗优先审评资格大冢制药（Otsuka Pharmaceutical）今日宣布，美国FDA已受理其在研单抗sibeprenlimab的生物制品许可申请（BLA），用于治疗免疫球蛋白A（IgA）肾病成人患者。FDA并授予该申请优先审评资格，PDUFA日期为2025年11月28日。根据新闻稿，若获批，sibeprenlimab将为患者提供一种每四周一次、便捷的预充式单剂量皮下注射剂，适用于居家自我给药。IgA肾病是全世界原发性肾小球肾炎最常见的形式，也是年轻人肾衰竭的最常见原因之一。这是一种进展性自身免疫性慢性肾病，随着大多数患者的疾病发展，可能导致终末期肾病（ESKD）。该BLA得到3期VISIONARY临床试验与2期ENVISION临床试验结果的支持。分析显示，VISIONARY试验达到主要终点，与安慰剂相比，患者在接受sibeprenlimab治疗九个月后，24小时尿蛋白肌酐比值（uPCR）呈现统计学显著且具临床意义的降低。  Sibeprenlimab是一种在研人源化单克隆抗体，它能阻断细胞因子A增殖诱导配体（APRIL）的作用。APRIL是一种免疫细胞生长因子，被认为在IgA肾病的发生和发展中起着关键作用。通过减少病理性半乳糖缺陷性IgA1（Gd-IgA1）的生成，sibeprenlimab有望帮助减缓肾脏损伤，并延缓疾病向终末期肾病的进展。美国FDA在去年2月授予sibeprenlimab突破性疗法认定（BTD）用于治疗IgA肾病。据公开资料显示，sibeprenlimab最初由Visterra公司开发。2018年，大冢制药宣布以约4.3亿美元的款项收购Visterra公司，从而获得包括sibeprenlimab在内一系列针对IgA肾病和其他肾脏疾病等适应症的在研产品。礼来10亿美元囊获小分子抑制剂礼来公司（Eli Lilly and Company）与SiteOne Therapeutics今日宣布，双方已达成最终协议，礼来将以总额高达10亿美元款项收购SiteOne。此次交易将使礼来囊获包括STC-004在内的管线，这是一款已准备进入2期临床的Nav1.8抑制剂，用于疼痛治疗。STC-004有望成为新一代非阿片类治疗药物，为慢性疼痛患者提供新的治疗选择。该交易将进一步加强礼来在非阿片类疼痛治疗药物领域的研发布局。SiteOne Therapeutics是一家临床阶段的生物医药公司，致力于开发一类新型、高选择性的小分子抑制剂，靶向Nav1.7、Nav1.8及其他离子通道，用于治疗疼痛、咳嗽以及其他与外周神经系统兴奋性过高相关的疾病。自成立以来，该公司专注于开发安全又有效的疼痛治疗药物，避免阿片类药物所带来的成瘾风险和不良反应。公司同时还在推进其他创新候选药物，这些候选药物对特定离子通道亚型具有高度选择性，用于治疗如慢性咳嗽、慢性眼表疼痛等感觉系统兴奋性障碍。渤健达超10亿美元RNAi疗法合作协议今日，渤健（Biogen）与City Therapeutics宣布达成战略合作协议，双方将联合开发若干新型RNA干扰（RNAi）疗法。City Therapeutics是一家生物医药公司，致力于通过下一代RNAi触发分子的优化，提升RNAi疗法的效果与适用范围。公司正积极构建一条创新的RNAi疗法管线，旨在为多个治疗领域的患者带来显著影响。根据合作协议，City Therapeutics将利用其下一代RNAi工程技术，开发RNAi触发分子，并与渤健的专有药物递送技术相结合。此次合作初期将聚焦于一个关键靶点，该靶点在中枢神经系统疾病中起重要作用。该项目将采用组织增强型递送技术，目标是实现系统性给药。根据协议，渤健将负责IND所需的临床前研究、全球临床开发、监管申报以及后续的商业化相关全部事务。根据协议条款，City Therapeutics将获得总计4600万美元的款项，其中包括1600万美元的首付款，以及总额达10亿美元的里程碑等款项。参考资料：[1] Otsuka Files Biologics License Application (BLA) for Sibeprenlimab in the Treatment of Immunoglobulin A Nephropathy. Retrieved May 27, 2025 from https://www.otsuka-us.com/news/otsuka-files-biologics-license-application-bla-sibeprenlimab-treatment-immunoglobulin[2] Lilly to expand its pain pipeline with acquisition of SiteOne Therapeutics. Retrieved May 27, 2025 from https://investor.lilly.com/news-releases/news-release-details/lilly-expand-its-pain-pipeline-acquisition-siteone-therapeutics[3] Biogen and City Therapeutics Announce Strategic Research Collaboration to Develop Select Novel RNAi-based Therapies. Retrieved May 27, 2025 from https://www.citytx.com/news/biogen-and-city-therapeutics-announce-strategic-research-collaboration-to-develop-select-novel-rnai-based-therapies免责声明：本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。👇 分享，点赞，在看，聚焦全球生物医药健康创新