• 12-month interim analysis outcomes for the novel APRIL antibody drug candidate sibeprenlimab, targeting IgA nephropathy, as part of the Phase 3 VISIONARY trial
• Study outcome on proteinuria measured at 12 months demonstrated that sibeprenlimab achieved a 54.3% (95% confidence interval [CI], 46.4% to 60.9%) placebo-adjusted reduction. The safety profile was favorable and consistent with placebo
• Trial outcomes presented at a late-breaking presentation session of the American Society of Nephrology (ASN) Kidney Week, November 6 to 9, 2025
• Proteinuria reduction is a recognized surrogate marker correlating with delaying progression to kidney failure
• Otsuka filed a Biologics License Application (BLA) for sibeprenlimab with the U.S. FDA and received a Priority Review designation from the agency, with a target action date (PDUFA date) of November 28, 2025

Otsuka Pharmaceutical, Co. Ltd. (Otsuka) announces that findings from a 12-month interim analysis of sibeprenlimab for the treatment of immunoglobulin A nephropathy (IgAN) in adults were presented in a late-breaking presentation session at the 2025 American Society of Nephrology (ASN) annual Kidney Week meeting in Houston, Texas. Summary data was simultaneously published in the online version of The New England Journal of Medicine.¹

Twelve-month data on proteinuria levels, measured as urine-protein-to-creatinine ratio in 24-hour urine collections (uPCR-24), as well as on safety, from the Phase 3 VISIONARY study (NCT05248646) of sibeprenlimab were presented.

At 12 months, sibeprenlimab showed a reduction in uPCR-24h of 56.6% (95% CI, 50.8% to 61.7%) compared with 5.1% (-6.7% to 15.7%) for placebo, corresponding to a placebo-adjusted reduction in uPCR-24h of 54.3% (95% CI, 46.4% to 60.9%). The safety profile was favorable and consistent with placebo. At the time of the interim analysis cutoff, the incidence of treatment-emergent adverse events in the safety set (n=510) was similar in the sibeprenlimab (74.1%) and placebo (82.1%) groups, the majority of which were mild to moderate in severity. The most common events were upper respiratory tract infections (14.7% for sibeprenlimab vs. 13.9% for placebo) and nasopharyngitis (12.4% for sibeprenlimab vs. 10.0% for placebo).

The 9-month interim analysis results for sibeprenlimab were submitted as part of the BLA (Biologics License Application) submission to the U.S. FDA. The VISIONARY study, the largest Phase 3 IgAN trial conducted to date, also showed that patients taking sibeprenlimab experienced substantially reduced serum immunoglobulins (IgA, IgG, IgM), A PRoliferation-Inducing Ligand (APRIL), galactose-deficient IgA1 (Gd-IgA1) and rates of hematuria, and delivered higher proteinuric remission versus placebo, which is consistent with APRIL inhibition.

Consistent treatment effects with Sibeprenlimab at nine-month effects were seen across prespecified subgroups, including those patients prescribed or not prescribed SGLT2 inhibitors, varying baseline proteinuria and estimated glomerular filtration rate (eGFR), demographics, and prior immunosuppression.

Sibeprenlimab works by blocking APRIL, which plays a key role in the process of IgAN pathogenesis and is an important initiating and sustaining factor in IgAN progression by promoting the production of pathogenic galactose-deficient IgA1 (Gd-IgA1).

Inhibition of APRIL results in reduced levels of galactose-deficient IgA1 (Gd-IgA1), which is implicated in the pathogenesis of IgAN.⁷ Sibeprenlimab is administered in a single-dose prefilled syringe for subcutaneous injection every four weeks intended for self-administration.

Otsuka filed a Biologics License Application (BLA) for sibeprenlimab with the U.S. FDA and received a Priority Review designation from the agency, with a target action date (PDUFA date) of November 28, 2025.

The VISIONARY study continues in a blinded manner to evaluate the change in kidney function over 24 months as measured by eGFR and is expected to be completed in 2026. Further prespecified and exploratory analyses of the data will be conducted to determine the full potential of sibeprenlimab for the treatment of IgAN.

About the VISIONARY Study

The VISIONARY study is a multicenter, randomized, double-blind, placebo-controlled trial consisting of approximately 530 (510 in main cohort plus 20 in explanatory cohort) adult patients with IgAN who were receiving standard-of-care therapy (defined as maximally tolerated ACE inhibitor or ARB plus SGLT2 inhibitor, if prescribed), designed to evaluate the efficacy and safety of sibeprenlimab 400 mg administered subcutaneously every four weeks, compared to placebo.²

The primary efficacy endpoint is change in 24-hour uPCR at 9 months compared with baseline. The secondary endpoint is to evaluate the change in kidney function over 24 months, measured as annualized slope of eGFR estimated over ~24 months.² This is expected to be completed in 2026. Further prespecified and exploratory analyses of the data will be conducted to determine the full potential of sibeprenlimab for the treatment of IgAN. ¹

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, which plays a key role in the process of IgAN pathogenesis and is an important initiating and sustaining factor in IgAN progression.

By selectively binding and inhibiting APRIL, sibeprenlimab reduces the amount of immunoglobulin A (IgA) and Gd-IgA1 levels.^{1 7} By reducing the production of Gd-IgA1, sibeprenlimab may help slow kidney damage and progression toward end-stage kidney disease (ESKD). By inhibiting APRIL, sibeprenlimab may help address one of the IgAN-specific drivers for nephron loss. ^3,4,5,6

About IgAN and APRIL

IgAN is a progressive, immune-mediated, chronic kidney disease that manifests in adults typically aged 20-40 years and leads to ESKD over the lifetime of most patients.

IgAN is characterized by the accumulation of Gd-IgA1 complexes in the kidneys. IgAN can lead to progressive loss of kidney function and, eventually, ESKD, imposing a significant burden on patients.¹⁰ Despite supportive care, there is an unmet need for treatments that address the root causes of the condition. Continued research in the disease remains crucial to uncovering opportunities for advancement in our understanding and treatment of patients.

APRIL, a cytokine in the tumor necrosis factor (TNF) family, is integral to the pathogenesis and progression of IgAN. It promotes the survival and class switching of B cells to toward IgA-producing cells, particularly the pathogenic galactose-deficient IgA1 (Gd-IgA1) that forms immune complexes in the kidneys. ^7,8,9,10

About Otsuka

Otsuka Pharmaceutical Co., Ltd. is a total healthcare company that focuses on each individual's potential to enhance their well-being. Our medical-related business provides treatments and diagnostics for both physical and mental health. Our nutraceutical business supports daily health maintenance and improvement. Otsuka's unique products and services are based on scientific evidence, under the guidance of our corporate philosophy: Otsuka-people creating new products for better health worldwide.

For further information, please visit www.otsuka.co.jp/en/

1. Sibeprenlimab in IgA Nephropathy -- Interim Analysis of a Phase 3 Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2512133?query=featured_home
2. Otsuka Pharmaceutical Development & Commercialization, Inc. Visionary Study: Phase 3 Trial of Sibeprenlimab in Immunoglobulin A Nephropathy (IgAN). Clinicaltrials.gov. https://clinicaltrials.gov/study/NCT05248646?a=7
3. Thompson A, Carroll K, Inker LA, et al. Proteinuria Reduction as a Surrogate End Point in Trials of IgA Nephropathy. Clin J Am Soc Nephrol. 2019;14(3):469-481.doi:10.2215/CJN.08600718
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.
5. Chang S, Li XK. The Role of Immune Modulation in Pathogenesis of IgA Nephropathy (nih.gov)
6. Cheung CK, Barratt J, Liew A, Zhang H, Tesar V, Lafayette R. The role of BAFF and April in IGA nephropathy: Pathogenic mechanisms and targeted therapies. Frontiers in nephrology. February 1, 2024.
7. Mathur M, Barratt J, Chacko B, et al. A Phase 2 Trial of Sibeprenlimab in Immunoglobulin A Nephropathy Patients. NEJM. 2023 https://www.nejm.org/doi/full/10.1056/NEJMoa2305635
8. Pitcher, D. Braddon, et. al Long-term outcomes in IGA nephropathy. Clinical journal of the American Society of Nephrology: CJASN. https://pubmed.ncbi.nlm.nih.gov/37055195/.
9. Lai K. Iga nephropathy. Nature reviews. Disease primers. 2016
10. Cheung, Chee Kay & Boyd, JKF & Feehally, J.. (2012). Evaluation and management of IgA nephropathy. Clinical Medicine. 12. s27-s30. 10.7861/clinmedicine.12-6-s27.