Otsuka Pharmaceutical, Co. Ltd. (Otsuka) and Otsuka Pharmaceutical Development & Commercialization, Inc. and Otsuka Pharmaceutical, Co. Ltd., today announce positive topline interim data from the ongoing Phase 3 clinical trial of sibeprenlimab for the treatment of immunoglobulin A nephropathy (IgA nephropathy) in adults.

大冢制药株式会社（大冢）与大冢制药开发与商业化株式会社以及大冢制药株式会社今天宣布了 sibeprenlimab 用于治疗成人免疫球蛋白 A 肾病（IgA 肾病）的 3 期临床试验的积极顶线中期数据。

Sibeprenlimab is an investigational, anti-APRIL monoclonal antibody (A PRoliferation-Inducing Ligand) that blocks a key initiating step in the immune pathogenic cascade of IgA nephropathy by limiting Gd-IgA1 production and immune complex formation. IgA nephropathy is a progressive, autoimmune, chronic kidney disease that can lead to end-stage kidney disease (ESKD) over the lifetime of most patients.1,2,3,4 Otsuka was previously granted Breakthrough Therapy designation for sibeprenlimab following favorable results of the Phase 2 ENVISION clinical trial.

Sibeprenlimab 是一种在研抗 APRIL 单克隆抗体（A PR增殖诱导配体），可通过限制 Gd-IgA1 的产生和免疫复合物的形成来阻断 IgA 肾病免疫致病级联中的关键启动步骤。IgA 肾病是一种进行性、自身免疫性、慢性肾病，在大多数患者的一生中可导致终末期肾病 (ESKD)。1,2,3,4大冢此前因 sibeprenlimab 在第 2 阶段 ENVISION 临床试验中取得良好结果而获得了突破性治疗认证。

The pre-specified interim analysis review, conducted by an independent data monitoring committee, found that the Phase 3 VISIONARY study (NCT05248646) 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.5 The study, a multicenter, randomized, double-blind, placebo-controlled trial consisting of approximately 530 adult patients (largest of its kind) with IgA nephropathy who were receiving standard-of-care therapy (defined as maximally tolerated ACE inhibitor or ARB +/- SGLT2 inhibitor), was designed to evaluate the efficacy and safety of sibeprenlimab 400 mg administered subcutaneously every four weeks, compared to placebo. The primary efficacy endpoint was to evaluate the change in 24-hour uPCR at 9 months compared with baseline

独立数据监测委员会进行的预先指定的中期分析审查发现，第 3 阶段 VISIONARY 研究 (NCT05248646) 达到了其主要终点，表明与安慰剂相比，sibeprenlimab 在治疗 9 个月后使 24 小时 uPCR (尿蛋白与肌酸比率) 显著降低，且具有临床意义。5该研究是一项多中心、随机、双盲、安慰剂对照试验，约有 530 名（同类中规模最大的）IgA 肾病成年患者参与，他们正在接受标准治疗（定义为最大耐受 ACE 抑制剂或 ARB +/- SGLT2 抑制剂），旨在评估每四周皮下注射 400 毫克 sibeprenlimab 与安慰剂相比的疗效和安全性。主要疗效终点是评估 9 个月时 24 小时 uPCR 与基线相比的变化。

"The positive interim data from this trial suggest that by targeting APRIL, we could provide a new therapeutic strategy for people living with this progressive kidney disease," said John Kraus, M.D., Ph.D., executive vice president and chief medical officer, Otsuka Pharmaceutical Development & Commercialization, Inc. "We look forward to the completion of this study and reviewing the full results at a future timepoint. We are deeply appreciative to the patients with IgA nephropathy who participated in this trial, their caregivers, and investigators, all of whom continue to contribute greatly to this research."

大塚制药开发与商业化公司执行副总裁兼首席医疗官 John Kraus 医学博士表示：“本次试验的积极中期数据表明，通过针对 APRIL，我们可以为患有这种渐进性肾病的患者提供一种新的治疗策略。我们期待完成这项研究，并在未来某个时间点审查全部结果。我们非常感谢参与本次试验的 IgA 肾病患者、他们的护理人员和研究人员，他们都将继续为这项研究做出巨大贡献。”

Brian Pereira, M.D., CEO of Visterra, Inc., an Otsuka U.S. affiliate, which designed and engineered sibeprenlimab, said, "We are encouraged by sibeprenlimab's continuing progress and its potential to provide a needed and possibly disease-modifying treatment option to IgA nephropathy patients."

设计和制造 sibeprenlimab 的大冢美国子公司 Visterra, Inc. 首席执行官医学博士 Brian Pereira 表示：“sibeprenlimab 的持续进展及其为 IgA 肾病患者提供所需、可能改善病情的治疗选择的潜力令我们感到鼓舞。

The ongoing Phase 3 study continues in a blinded manner to evaluate the change in kidney function over 24 months as measured by estimated glomerular filtration rate (eGFR) and is expected to be completed in early 2026. Further prespecified and exploratory analyses of the data will be conducted to determine the full potential of sibeprenlimab for the treatment of IgA nephropathy. Otsuka plans to review interim analysis results with the FDA to enable a potential regulatory submission for accelerated approval.

正在进行的 3 期研究继续以盲法方式评估 24 个月内肾功能的变化（以估计肾小球滤过率 (eGFR) 衡量），预计将于 2026 年初完成。将对数据进行进一步的预先指定和探索性分析，以确定 sibeprenlimab 在治疗 IgA 肾病方面的全部潜力。大冢计划与 FDA 一起审查中期分析结果，以便提交潜在的监管申请，以加速批准。