Zenyaku Kogyo Co., Ltd. (Japanese-only website) and Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) announced today that Zenyaku obtained regulatory approval from the Ministry of Health, Labour and Welfare (MHLW), for an anti-CD20 monoclonal antibody Rituxan® intravenous injection 100 mg and 500 mg [generic name: rituximab (genetical recombination)] (hereafter, “Rituxan”) for “refractory steroid-resistant nephrotic syndrome*1.”

全药工业株式会社（仅限日语网站）和中外制药株式会社（东京证券交易所股票代码：4519）今天宣布，全药工业已获得厚生劳动省 (MHLW) 的监管批准，用于治疗“难治性类固醇耐药性肾病综合征*1 ”的抗 CD20 单克隆抗体Rituxan®静脉注射剂 100 毫克和 500 毫克 [通用名：利妥昔单抗（基因重组）]（以下简称“Rituxan”）。

Nephrotic syndrome is a general term for a condition in which damage to the glomerular slit membrane in the nephrons that make up the kidneys results in severe proteinuria and hypoalbuminemia, leading to generalized edema1). Nephrotic syndrome that develops in childhood is the most common chronic kidney disease in children2) and is a designated intractable disease of unknown cause. Approximately 10% to 20% are classified as “steroid-resistant nephrotic syndrome,” in which complete remission cannot be achieved with steroid treatment, which is the first-choice drug3). Steroid pulse therapy or remission induction therapy using immunosuppressants are recommended for “steroid-resistant nephrotic syndrome,” but in cases of “refractory steroid-resistant nephrotic syndrome” where remission cannot be achieved even with these treatments, there is a high risk of developing end-stage renal failure and the prognosis is poor3).

肾病综合征是指肾脏的肾单位中的肾小球裂孔膜受到损害，从而出现严重蛋白尿和低白蛋白血症，并引发全身水肿1) 的一种疾病的总称。儿童期发病的肾病综合征是儿童中最常见的慢性肾脏疾病2)，是一种原因不明的难治性疾病。约10%～20%的患者被归类为“类固醇耐药性肾病综合征”，使用首选药物类固醇治疗无法完全缓解3)。对于“类固醇耐药性肾病综合征”，建议使用类固醇冲击疗法或使用免疫抑制剂的缓解诱导疗法，但在即使使用这些疗法也无法缓解的“难治性类固醇耐药性肾病综合征”病例中，发生终末期肾衰竭的风险很高，预后不良3)。

Rituxan is an anti-CD20 monoclonal antibody that specifically binds to CD20, a protein expressed on B cells, excluding hematopoietic stem cells and plasma cells. It attacks target B cells using the immune system equipped with the human body, and damages cells. It has been suggested that B cells may be involved in the pathogenesis and disease activity of nephrotic syndrome4) 5) 6), and it is expected that removing B cells with Rituxan will have a therapeutic effect on nephrotic syndrome.

Rituxan 是一种抗 CD20 单克隆抗体，可特异性结合 CD20，CD20 是一种在 B 细胞（不包括造血干细胞和浆细胞）上表达的蛋白质。它利用人体配备的免疫系统攻击目标 B 细胞并破坏细胞。有研究表明 B 细胞可能参与肾病综合征的发病机制和疾病活动4) 5) 6)，预计使用 Rituxan 去除 B 细胞将对肾病综合征产生治疗作用。

Rituxan was approved in August 2014 for the treatment of childhood-onset “refractory nephrotic syndrome (frequently relapsing or steroid-dependent).” In the development of Rituxan for “refractory steroid-resistant nephrotic syndrome,” the primary endpoint (reduction rate from baseline in urinary protein creatinine ratio at 169 days) was achieved7) 8) in an investigator-initiated clinical trial*2 targeting patients with childhood-onset refractory steroid-resistant nephrotic syndrome. Zenyaku filed an application for partial changes to the manufacturing and sales approval items on December 22, 2023, which led to the current approval.

Rituxan 于 2014 年 8 月获批用于治疗儿童期发病的“难治性肾病综合征（复发频繁或依赖类固醇）”。在 Rituxan 用于“难治性类固醇耐药性肾病综合征”的开发中，在针对儿童期发病的难治性类固醇耐药性肾病综合征患者的研究者发起的临床试验*2中，实现了主要终点（169 天时尿蛋白肌酐比相对于基线的降低率） 7) 8)。Zenyaku 于 2023 年 12 月 22 日提交了部分制造和销售批准项目变更申请，从而获得了目前的批准。

Zenyaku and Chugai will continue working closely together so that Rituxan can further contribute to the treatment of refractory nephrotic syndrome.

Zenyaku 和 Chugai 将继续密切合作，以便 Rituxan 能够为难治性肾病综合征的治疗做出进一步贡献。