PRINCETON, N.J. & WALTHAM, Mass.--(BUSINESS WIRE)--Otsuka Pharmaceutical Development & Commercialization, Inc. and Visterra Inc., today announced that the full results of a Phase 2 trial of sibeprenlimab (VIS649) for treatment of immunoglobulin A nephropathy (IgAN; Berger’s disease) have been published in the New England Journal of Medicine.1 The topline findings will also be presented in a late-breaking poster session at the American Society of Nephrology (ASN) Kidney Week meeting in Philadelphia, PA..

普林斯顿，新泽西州和沃尔瑟姆，马萨诸塞州-（商业线）-大冢制药开发和商业化公司和Visterra公司。，今天宣布，用于治疗免疫球蛋白a肾病（IgAN；Berger病）的sibeprelimab（VIS649）2期临床试验的全部结果已发表在新英格兰医学杂志上.1顶级研究结果也将在美国宾夕法尼亚州费城美国肾脏病学会（ASN）肾脏周会上的最新海报会议。。

Sibeprenlimab is an investigational humanized monoclonal antibody that blocks the action of the cytokine A Proliferation Inducing Ligand (APRIL), an immune cell growth factor believed to play a key role in the development and progression of IgAN.1,4,5

Sibeprenlimab是一种研究性人源化单克隆抗体，可阻断细胞因子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IgAN的发生和发展中起关键作用.1,4,5

The Phase 2 trial randomized 155 adult participants with biopsy-confirmed IgAN to monthly intravenous injections of sibeprenlimab 2, 4, or 8 mg/kg, or placebo for 12 months. The primary outcome measure was the change from baseline in 24-hour urine protein-to-creatinine ratio (uPCR) at month 12. Secondary outcomes included safety and change in estimated glomerular filtration rate (eGFR), a measure of kidney function.1.

第二阶段试验将155名活检证实为IgAN的成年受试者随机分配到每月静脉注射sibeprelimab 2,4或8 mg/kg或安慰剂12个月。主要结局指标是第12个月24小时尿蛋白与肌酐比值（uPCR）从基线的变化。次要终点包括安全性和估计肾小球滤过率（eGFR）的变化，这是衡量肾功能的指标。

The study results demonstrated that 12 months of sibeprenlimab treatment in patients with IgAN resulted in significant reductions in proteinuria compared to placebo. At 12 months, geometric mean ratio reduction in 24-hour uPCR from baseline was 47.2%, 58.8%, 62.0%, and 20.0% with sibeprenlimab 2, 4, and 8 mg/kg, and placebo, respectively.1.

研究结果表明，与安慰剂相比，IgAN患者12个月的sibeprenimab治疗导致蛋白尿显着减少。在12个月时，与基线相比，24小时uPCR的几何平均比率降低分别为47.2%，58.8%，62.0%和20.0%，分别为sibeprelimab 2,4和8 mg/kg和安慰剂。

Beneficial changes in eGFR were also observed in the sibeprenlimab groups compared to placebo. The annual eGFR change was −2.7, +0.2, −1.5, and −7.4 ml/1.73 m2 with sibeprenlimab 2, 4, and 8 mg/kg, and placebo, respectively. This reflects a stabilization of eGFR with sibeprenlimab compared to the eGFR decline observed with placebo.1.

与安慰剂相比，在sibeprelimab组中也观察到eGFR的有益变化。sibeprenlimab 2、4和8 mg/kg和安慰剂的年eGFR变化分别为-2.7，+0.2，-1.5和-7.4 ml/1.73 m2。这反映了与安慰剂组观察到的eGFR下降相比，sibeprelimab的eGFR稳定。

The incidence of treatment-emergent adverse events (TEAEs) for patients on sibeprenlimab and placebo was similar. The safety profile of sibeprenlimab showed no evidence of undesirable toxicity or clinically meaningful immunosuppression during this trial and follow-up through month 16.1

sibeprenlimab组和安慰剂组患者的治疗紧急不良事件（TEAE）发生率相似。Sibeprelimab的安全性显示在该试验期间和第16.1个月的随访期间没有不良毒性或临床上有意义的免疫抑制的证据

“IgAN is the most common form of primary glomerulonephritis and is associated with a significant reduction in life expectancy,” said Brian J. G. Pereira, M.D., CEO of Visterra, Inc., and the senior author of the New England Journal of Medicine paper. “Current therapies have modest efficacy, at best, in reducing the rate of chronic kidney disease progression and new disease-specific targeted treatment options would be hugely beneficial.”.

Visterra，Inc.首席执行官，新英格兰医学杂志高级作者Brian J.G.Pereira博士说：“IgAN是最常见的原发性肾小球肾炎形式，与预期寿命显着降低有关。“目前的疗法在降低慢性肾脏疾病进展速度方面效果不佳，新的疾病特异性靶向治疗方案将是非常有益的。”。

“We are excited by these results, which bring us one step closer to addressing the critical unmet treatment needs of patients with this complex, life-threatening condition,” said John Kraus, M.D., Ph.D., executive vice president and chief medical officer, Otsuka Pharmaceutical Development & Commercialization, Inc.

大冢制药开发与商业化公司执行副总裁兼首席医疗官约翰·克劳斯博士说：“我们对这些结果感到兴奋，这使我们更接近解决患有这种复杂威胁生命的疾病患者的关键未满足治疗需求。”。

'We look forward to continuing to evaluate the potential of sibeprenlimab in the ongoing Phase 3 trial program.'.

“我们期待继续评估正在进行的3期试验计划中sibeprelimab的潜力。”。

About Immunoglobulin A Nephropathy

关于免疫球蛋白A肾病

Immunoglobulin A nephropathy (IgAN; Berger’s disease) is the most common form of primary glomerulonephritis worldwide and is the most common cause of kidney failure in young adults.1,2 The disease is associated with a reduction in life expectancy of 10 years,3 with at least 30% of affected patients progressing to kidney failure within 20 to 30 years, despite optimized standard of care therapy.6,7.

免疫球蛋白A肾病（IgAN；Berger's disease）是世界范围内最常见的原发性肾小球肾炎，也是年轻人肾功能衰竭的最常见原因.1,2该疾病与10年预期寿命缩短有关，3至少30%的受影响患者在20至30年内发展为肾功能衰竭，尽管优化了护理标准治疗.6,7。

Current standard of care management is based on renin-angiotensin aldosterone system (RAAS) blockers and adequate blood pressure control, but the risk of kidney failure remains high.8

目前的护理管理标准是基于肾素-血管紧张素醛固酮系统（RAAS）阻滞剂和适当的血压控制，但肾衰竭的风险仍然很高。8

About Sibeprenlimab

关于Sibepenlimab

Sibeprenlimab (VIS649) is an investigational humanized immunoglobulin G (IgG2) monoclonal antibody that binds to and blocks the biological actions of the cytokine A PRoliferation Inducing Ligand (APRIL), a key factor in the production of galactose-deficient IgA1 (Gd-IgA1), which has been demonstrated to play a key role in the pathogenesis of IgAN.1,4,5.

Sibeprenlimab（VIS649）是一种研究性人源化免疫球蛋白G（IgG2）单克隆抗体，可结合并阻断细胞因子A增殖诱导配体（APRIL）的生物学作用，APRIL是产生半乳糖缺陷型IgA1的关键因子（Gd-IgA1），已被证明在IgAN的发病机制中起关键作用.1,4,5。

About the Phase 2 Sibeprenlimab Trial

关于第二阶段sibeprelimab试验

The multicenter, randomized, double-blind, placebo-controlled, multiple-dose, parallel-group study was conducted in adults with biopsy-confirmed IgAN at high risk of disease progression, despite having received standard-of-care treatment. Participants were randomized 1:1:1:1 to intravenous sibeprenlimab 2, 4, or 8 mg/kg or placebo monthly for 12 months.9.

这项多中心，随机，双盲，安慰剂对照，多剂量，平行组研究是在接受标准护理治疗的活检证实IgAN处于疾病进展高风险的成人中进行的。参与者每月以1:1:1:1的比例随机分配到静脉注射sibeprelimab 2,4或8 mg/kg或安慰剂，持续12个月。

The study was designed to test the safety and efficacy of different doses of sibeprenlimab. The main objectives were to evaluate the safety and tolerability of sibeprenlimab and to evaluate the dose response to different doses of sibeprenlimab on proteinuria and eGFR.9

该研究旨在测试不同剂量西贝拉利单抗的安全性和有效性。主要目的是评估西贝拉利单抗的安全性和耐受性，并评估不同剂量西贝拉利单抗对蛋白尿和eGFR的剂量反应

The study was comprised of three main periods, Screening, Treatment (12 months) and Follow-Up (4 months). The findings from this study form the basis for the subsequent clinical development of sibeprenlimab.9

该研究包括三个主要阶段，筛查，治疗（12个月）和随访（4个月）。本研究的结果为西贝拉利马的后续临床开发奠定了基础

About Otsuka

关于大冢

Otsuka Pharmaceutical Co., Ltd. is a global healthcare company with the corporate philosophy of “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..

大冢制药有限公司是一家全球性的医疗保健公司，其公司理念是“大冢-人们为全球健康创造新产品”。大冢研究，开发，制造和销售创新产品，重点是满足未满足的医疗需求的药品和用于维持日常健康的营养保健品。。

In pharmaceuticals, Otsuka is a leader in the challenging areas of CNS, kidney 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..

在制药领域，大冢是中枢神经系统，肾脏和心血管健康等具有挑战性的领域的领导者，并且在肿瘤学和包括结核病在内的一些未得到充分解决的疾病方面拥有额外的研究计划，这是一个重要的全球公共卫生问题。这些承诺说明了大冢是一家真正的“大风险”公司，在其所做的一切中都运用年轻的创造力精神。。

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’ 2,000 employees in the U.S. develop and commercialize medicines in the areas of mental health and kidney diseases, using cutting-edge technology to address unmet healthcare needs..

大冢于1973年在美国成立，今天其美国分支机构包括大冢制药开发和商业化公司（OPDC）和大冢美国制药公司（OAPI）。这两家公司在美国的2000名员工利用尖端技术开发和商业化精神卫生和肾脏疾病领域的药物，以解决未满足的医疗需求。。

OPDC and OAPI are indirect subsidiaries of Otsuka Pharmaceutical Company, Ltd., which is a subsidiary of Otsuka Holdings Co., Ltd. headquartered in Tokyo, Japan. The Otsuka group of companies employed 47,000 people worldwide and had consolidated sales of approximately USD 13.1 billion in 2022.

OPDC和OAPI是大冢制药有限公司的间接子公司，大冢制药有限公司是大冢控股有限公司的子公司，总部设在日本东京。大冢集团在全球雇用了47000人，到2022年合并销售额约为131亿美元。

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 X at @OtsukaUS. Otsuka Pharmaceutical Co., Ltd.’s global website is accessible at https://www.otsuka.co.jp/en/.

所有大冢故事都是从少走的道路开始的。了解有关美国大冢的更多信息，请访问www.Otsuka-us.com，并通过LinkedIn和X at@OtsukaUS与我们联系。大冢制药有限公司的全球网站可在https://www.otsuka.co.jp/en/.

About Visterra

Visterra

Visterra is a clinical-stage biotechnology company and a wholly owned subsidiary of Otsuka America Pharmaceutical, Inc. committed to developing innovative antibody-based therapies for the treatment of patients with kidney diseases and other hard-to-treat autoimmune 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.

Visterra是一家临床阶段生物技术公司，是Otsuka America Pharmaceutical，Inc。的合资子公司，致力于开发创新的基于抗体的疗法，用于治疗肾病和其他难以治疗的自身免疫性疾病患者。其专有的Hierotope®平台能够设计和设计精确的基于生物制剂的候选产品，这些产品特异性结合并调节传统治疗方法未充分解决的关键疾病目标。

The platform also includes Fc engineering capabilities for half-life extension, bispecific antibodies and antibody-drug conjugates (ADCs). Visterra’s pipeline includes programs targeting IgA nephropathy and other kidney diseases, immunologically-driven diseases and infectious diseases. Prior to its acquisition by Otsuka, Visterra was funded by investments by Polaris Partners, Flagship Pioneering, the Bill and Melinda Gates Foundation, MRL Ventures Fund, Vertex Ventures HC, Serum Institute of India Private Ltd., Temasek Holdings, Omega Funds, Cycad Group, Lux Capital, Alleghany Financial Group Ventures, CTI Life Sciences Fund and Alexandria Equities.

该平台还包括用于延长半衰期的Fc工程能力，双特异性抗体和抗体-药物偶联物（ADC）。Visterra的管道包括针对IgA肾病和其他肾脏疾病，免疫驱动疾病和传染病的项目。在被大冢收购之前，Visterra由Polaris Partners，Flagship Expandering，Bill and Melinda Gates Foundation，MRL Ventures Fund，Vertex Ventures HC，Serum Institute of India Private Ltd.，Temasek Holdings，Omega Funds，Cycad Group，Lux Capital，Alleghany Financial Group Ventures，CTI Life Sciences Fund和Alexandria Equity。

For more information, visit www.visterrainc.com..

欲了解更多信息，请访问www.visterrainc.com。。

References

工具书类

1.

1.

Mathur M, Barratt J, Chacko B, et al. A Phase 2 Trial of Sibeprenlimab in Immunoglobulin A Nephropathy Patients. NEJM. 2023

Mathur M，Barratt J，Chacko B等人，Sibeprenlimab在免疫球蛋白A肾病患者中的2期临床试验。NEJM。2023

2.

2.

Floege J, Amann K. Primary glomerulonephritides. Lancet. 2016;387(10032):2036-2048.

Floege J，Amann K.原发性肾小球肾炎。柳叶刀。2016;387(10032):2036-2048.

3.

3.

Hastings MC, Bursac Z, Julian BA, et al. Life Expectancy for Patients From the Southeastern United States With IgA Nephropathy. Kidney Int Rep. 2017;3(1):99-104.

Hastings MC，Bursac Z，Julian BA等人。来自美国东南部的IgA肾病患者的预期寿命。Kidney Int Rep。2017；3(1):99-104.

4.

4.

Mathur M, Barratt J, Suzuki Y, et al. Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of VIS649 (Sibeprenlimab), an APRIL-Neutralizing IgG2 Monoclonal Antibody, in Healthy Volunteers. Kidney Int Rep. 2022;7(5):993-1003.

Mathur M，Barratt J，Suzuki Y等人。健康志愿者中VIS649（sibeprelimab）（一种APRIL中和IgG2单克隆抗体）的安全性，耐受性，药代动力学和药效学。Kidney Int Rep.2022；7(5):993-1003.

5.

5.

Chang S, Li XK. The Role of Immune Modulation in Pathogenesis of IgA Nephropathy. Front Med (Lausanne). 2020;7:92.

Chang S，Li XK。免疫调节在IgA肾病发病机制中的作用。Front Med（洛桑）。2020;7:92.

6.

6.

Lai KN, Tang SC, Schena FP, et al. IgA nephropathy. Nat Rev Dis Primers. 2016;2:16001.

赖KN，唐SC，Schena FP，等IgA肾病。Nat Rev Dis引物。2016;2:16001.

7.

7.

Gleeson PJ, O'Shaughnessy MM, Barratt J. IgA nephropathy in adults - Treatment Standard [published online ahead of print, 2023 Jul 7].

Gleeson PJ，O'Shaughnessy MM，Barratt J.IgA成人肾病-治疗标准[在线印刷前发布，2023年7月7日]。

8.

8.

Rizk DA, Perkovic V, Lafayette R, et al. A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Sibeprenlimab Administered Subcutaneously in Patients With IgAN. Presented at the ASN Kidney Week 2022, November 3–6, 2022, Orlando, FL.

Rizk DA，Perkovic V，Lafayette R等人。第3阶段，多中心，随机，双盲，安慰剂对照研究，以评估皮下注射西贝瑞单抗治疗IgAN患者的疗效和安全性。于2022年11月3日至6日在佛罗里达州奥兰多举行的ASN肾脏周2022上发表。

9.

9.

ClinicalTrials.gov. National Library of Medicine (U.S.). Safety and Efficacy Study of VIS649 for IgA Nephropathy Identifier: NCT04287985. https://classic.clinicaltrials.gov/ct2/show/NCT04287985.

ClinicalTrials.gov。国家医学图书馆（美国）.VIS649对IgA肾病标识符的安全性和有效性研究：NCT04287985。https://classic.clinicaltrials.gov/ct2/show/NCT04287985.