Anti-CD20 Monoclonal Antibody Rituxan^® Approved for Adult-onset Frequently Relapsing or Steroid-dependent Nephrotic Syndrome

TOKYO, June 19, 2026 -- Zenyaku Kogyo Co., Ltd. (website in Japanese only) and Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) announced today that Zenyaku, the marketing authorization holder, obtained regulatory approval from the Ministry of Health, Labour and Welfare (MHLW), for an additional dosage and administration^*1 of an anti-CD20 monoclonal antibody Rituxan^® intravenous infusion 100 mg and 500 mg [generic name: rituximab (genetical recombination)] (hereafter “Rituxan”), which is co-promoted by both companies, for adult-onset frequently relapsing or steroid-dependent nephrotic syndrome.

Nephrotic syndrome is a general term for a condition characterized by massive proteinuria due to increased permeability of the glomerular capillary wall and hypoproteinemia (hypoalbuminemia), resulting in renal dysfunction (chronic kidney disease and acute kidney injury), edema, dyslipidemia, coagulation abnormalities (thrombotic tendency), endocrine abnormalities, immunodeficiency, and increased susceptibility to infections¹⁾. It is classified into primary (idiopathic) nephrotic syndrome, in which no underlying disease is identified, and secondary nephrotic syndrome, which is caused by an identifiable underlying disease¹⁾. Primary nephrotic syndrome is further classified histopathologically into minimal change nephrotic syndrome, focal segmental glomerulosclerosis, membranous nephropathy, or membranoproliferative glomerulonephritis, and treatment policies are determined based on the steroid responsiveness of each type¹⁾²⁾. In these pathological types, some patients achieve remission after steroid administration, but show frequent relapses shortly thereafter or relapse upon tapering or discontinuation of steroids, resulting in steroid dependence. Immunosuppressants are considered for such patients; however, there remains a need for new treatment options due to concerns regarding adverse effects such as nephrotoxicity and gonadal toxicity²⁾.

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 eliminates target B cells through the body’s immune system. B cells are suggested to be involved in the pathogenesis and disease activity of nephrotic syndrome, and depletion of B cells by Rituxan is expected to contribute to its treatment³⁾⁴⁾⁵⁾.
Rituxan was approved in August 2014 for pediatric-onset refractory nephrotic syndrome (frequently relapsing or steroid-dependent), in September 2024 for pediatric-onset refractory nephrotic syndrome (steroid-resistant), and in March 2025 for pediatric-onset non-refractory frequently relapsing or steroid-dependent nephrotic syndrome. Most recently, Zenyaku has obtained additional approval for the treatment of adult-onset frequently relapsing or steroid-dependent nephrotic syndrome.

For adult-onset frequently relapsing or steroid-dependent nephrotic syndrome, an investigator-initiated clinical trial^*2 demonstrated that the relapse-free rate at Week 49, the primary endpoint, was significantly higher in the Rituxan group than in the placebo group (Rituxan group: 87.4% [95% CI: 69.8-95.1%]; placebo group: 38.0% [95% CI: 22.1-53.8%]; p<0.0001 [log-rank test, one-sided significance level of 2.5%]), indicating a relapse-preventive effect of Rituxan. Although the incidence of adverse events and adverse drug reactions tended to be higher in the Rituxan group than in the placebo group, the safety profile was consistent with previously reported safety data for approved indications of Rituxan in Japan and overseas, and no new safety concerns were identified. Based on these results, Zenyaku filed a partial change application for manufacturing and marketing approval on June 30, 2025, leading to this approval.

Zenyaku and Chugai will work together so that Rituxan can further contribute to the treatment of nephrotic syndrome.

Trademarks used or mentioned in this release are protected by law.

1. *1 Dosage and administration for nephrotic syndrome
   ○Nephrotic Syndrome
   • Frequently relapsing or steroid-dependent nephrotic syndrome
     Rituximab (genetical recombination) is usually administered at a dose of 375 mg/m² (maximum 500 mg in pediatric-onset cases) by intravenous infusion twice at 1-week intervals. Thereafter, for adult-onset cases, a dose of 375 mg/m² is administered once by intravenous infusion 6 months after the initial dose.
   • Refractory nephrotic syndrome (frequently relapsing, steroid-dependent, or steroid-resistant)
     Rituximab (genetical recombination) is usually administered at a dose of 375 mg/m² by intravenous infusion four times at 1-week intervals. The maximum dose per administration is 500 mg.
   <Approved regimen for adult-onset nephrotic syndrome>
   Rituximab (genetical recombination) is usually administered at a dose of 375 mg/m² by intravenous infusion twice at 1-week intervals, followed by a single dose of 375 mg/m² by intravenous infusion 6 months after the initial dose.
2. *2 A Phase III clinical study (IDEC-C2B8-aNS1) evaluating the efficacy and safety of IDEC-C2B8 in patients with adult-onset nephrotic syndrome (frequently relapsing or steroid-dependent)⁶⁾⁷⁾.

Sources

1. I. Definition, Constituent Diseases, and Pathophysiology. 1.Definition, Constituent Diseases, and Pathophysiology. Narita K (supervisor), Department of Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences; Research Group on Intractable Renal Diseases, Health and Labour Sciences Research Grants for Research on Intractable Diseases (Policy Research Project on Intractable Diseases). Evidence-based Clinical Practice Guidelines for Nephrotic Syndrome 2020. Tokyo Igakusha, 2020, pp.1-7.
2. IV. Treatment. 1.Treatment Algorithm. Narita K (supervisor), Department of Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences; Research Group on Intractable Renal Diseases, Health and Labour Sciences Research Grants for Research on Intractable Diseases (Policy Research Project on Intractable Diseases). Evidence-based Clinical Practice Guidelines for Nephrotic Syndrome 2020. Tokyo Igakusha, 2020, pp.48-53.
3. Tani Y, Kida H, Abe T, et al. B lymphocyte subset patterns and their significance in idiopathic glomerulonephritis. Clin Exp Immunol. 1982; 48(1): 201-204.
4. Yokoyama H, Kida H, Tani Y, et al. Immunodynamics of minimal change nephrotic syndrome in adults T and B lymphocyte subsets and serum immunoglobulin levels. Clin Exp Immunol. 1985; 61(3): 601-607.
5. Garin EH, Diaz LN, Mu W, et al. Urinary CD80 excretion increases in idiopathic minimal-change disease. J Am Soc Nephrol. 2009; 20(2): 260-266.
6. Isaka Y, Sakaguchi Y, Shinzawa M, et al. Rituximab for Relapsing Nephrotic Syndrome in Adults: A Randomized Clinical Trial. JAMA. 2025 Dec 9;334(22):2011-2019.
7. Japan Registry of Clinical Trials (jRCT). Clinical Trials Submission and Disclosure System. https://jrct.mhlw.go.jp/en-latest-detail/jRCT2051200045 [Internet; cited June 2026]

[Reference Information]
Announcement of Termination of Co-Promotion of Rituxan^® in Japan (Anti-CD20 Monoclonal Antibody) (News release dated April 9, 2026)
Zenyaku Kogyo Co., Ltd.: https://www.zenyaku.co.jp/2026/04/09003301.html (Japanese only)
Chugai Pharmaceutical Co., Ltd.: https://www.chugai-pharm.co.jp/english/news/detail/20260409153000_1239.html