Sibeprenlimab

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

2025年3月31日，大冢制药及其子公司Otsuka Pharmaceutical Development & Commercialization, Inc.（OPDC）宣布已向美国食品药品监督管理局（FDA）提交了Sibeprenlimab的生物制品许可申请（BLA），用于治疗免疫球蛋白A肾病（IgAN）。Sibeprenlimab是一种研究中的单克隆抗体，能够选择性地抑制APRIL（A PRoliferation-Inducing Ligand）的活性。APRIL在IgAN的发病机制中扮演关键角色，是促进致病性Gd-IgA1产生和免疫复合物形成的重要启动和维持因子。Sibeprenlimab通过皮下注射给药，每四周一次，患者可以选择在家自我注射或由护理人员注射，提供了治疗的便利性。支持性临床试验‌Phase 2 ENVISION临床试验‌：该试验的结果支持了sibeprenlimab在IgAN治疗中的有效性和安全性，基于此FDA授予了sibeprenlimab突破性疗法认定。‌Phase 3 VISIONARY临床试验‌：这是一项多中心、随机、双盲、安慰剂对照的试验，纳入了约530名接受标准治疗的IgAN成人患者。试验结果表明，与安慰剂相比，sibeprenlimab在9个月时显著降低了24小时尿蛋白肌酐比（uPCR），且安全性良好。IgA肾病与APRILIgA肾病是一种进行性、自身免疫性、慢性肾脏疾病，主要影响20至40岁的成年人，并可能导致终末期肾病（ESKD）。该疾病的特点是肾脏中Gd-IgA1复合物的积累，导致肾脏功能逐渐丧失。尽管有支持性治疗，但针对疾病根本原因的治疗方法仍存在未满足的需求。APRIL作为一种细胞因子，在IgAN的发病和进展中起关键作用，通过促进B细胞的存活和类别转换产生IgA，特别是致病性Gd-IgA1。Otsuka表示，此次BLA的提交是公司致力于解决肾脏疾病未满足需求的重要里程碑。Sibeprenlimab通过其独特的机制抑制APRIL的活性，有望为IgAN患者提供一种新的治疗选择。Otsuka感谢所有参与这项重要研究的患者、护理人员和医疗专业人员，并期待FDA的审查结果。Sibeprenlimab的BLA提交标志着Otsuka在开发针对IgAN创新疗法方面取得了显著成就。如果获得批准，sibeprenlimab将成为首个针对IgAN中APRIL通路的治疗药物，为患者提供新的治疗选择和更好的疾病管理可能性。来源：https://ssl4.eir-parts.net/doc/4578/tdnet/2587246/00.pdf药事纵横投稿须知：稿费已上调，欢迎投稿