- VOYXACT is the first and only FDA-approved treatment for adults with primary IgAN at risk for disease progression that selectively inhibits A PRoliferation Inducing Ligand (APRIL), a key immune driver of the disease
- Interim analyses from the Phase 3 VISIONARY trial demonstrate faster and higher rates of microscopic hematuria negativity (0–5/HPF)
- Findings add to the growing body of evidence evaluating APRIL inhibition in adults with IgAN
PRINCETON, N.J.--(BUSINESS WIRE)--Otsuka Pharmaceutical Development & Commercialization, Inc. (Otsuka) today announced new analyses from the Phase 3 VISIONARY trial evaluating VOYXACT® (sibeprenlimab-szsi) in adults with IgA nephropathy (IgAN) at risk for disease progression, demonstrating clinically meaningful improvements across key markers of IgAN. These data, presented at the 2026 ISN World Congress of Nephrology (WCN’26), reinforce the potential of selectively inhibiting A PRoliferation Inducing Ligand (APRIL), a central driver of disease biology, to meaningfully impact patient outcomes1.
The interim analyses from the global Phase 3 VISIONARY trial demonstrated a higher and faster proportion of patients achieving negative microscopic hematuria (0–5/HPF), an exploratory endpoint reflecting improvement in glomerular injury in IgAN1. Among global patients with hematuria at baseline, 82.5% of patients receiving sibeprenlimab (33/40) were negative for microscopic hematuria at Week 48 compared with 52.6% of patients receiving placebo (51/97)1. Median time to achieve negativity for microscopic hematuria (0–5/HPF) was nine weeks with sibeprenlimab versus 24 weeks with placebo1. These findings complement robust proteinuria reductions observed with sibeprenlimab1. The safety profile was comparable between sibeprenlimab and placebo1.
“The new VISIONARY analyses highlight the differentiated clinical profile of sibeprenlimab and the potential clinical impact of targeting a key immune driver of the disease,” said John Kraus, M.D., Ph.D., executive vice president and chief medical officer, Otsuka. “In addition to meaningful reductions in proteinuria, the observed improvements in hematuria provide complementary evidence of an effect on underlying disease activity. Together, these findings reinforce the potential of VOYXACT to meaningfully improve clinical outcomes for adult IgAN patients at risk for disease progression.”
In a previously prespecified interim analysis of the global main cohort of the Phase 3 VISIONARY trial (NCT05248646) presented at the European Renal Association (ERA) congress in 2025, sibeprenlimab met the primary endpoint, demonstrating a -51.2% (P<0.0001) placebo-adjusted reduction in 24-hour urine protein-to-creatinine ratio (uPCR-24h) at nine months2. These findings underscore the clinical relevance of sibeprenlimab’s APRIL inhibition in a critical patient population1.
The VISIONARY trial is ongoing to evaluate the safety and efficacy of sibeprenlimab in preserving kidney function based on estimated glomerular filtration rate slope over a 24-month treatment period1.
About IgAN
IgAN is a progressive, immune-mediated, chronic kidney disease that typically manifests in adults aged 20-40 years. IgAN is characterized by the accumulation of Gd-IgA1 complexes in the kidneys3-5. Despite supportive care, there is an unmet need for treatments that address the root causes of the condition6. Continued research in the disease remains crucial to uncovering opportunities for advancement in our understanding and treatment of patients6.
About VOYXACT® (sibeprenlimab-szsi)
VOYXACT (sibeprenlimab-szsi) 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. VOYXACT is a humanized monoclonal antibody that binds to and blocks APRIL, which plays a key role in the 4-hit 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)6-9. Inhibition of APRIL results in reduced levels of serum galactose-deficient IgA1 (Gd-IgA1), which is implicated in the pathogenesis of IgAN. VOYXACT is a self-administered, subcutaneous injection dosed every four weeks.
INDICATION and IMPORTANT SAFETY INFORMATION for VOYXACT® (sibeprenlimab-szsi)
INDICATION
VOYXACT is indicated to reduce proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk for disease progression.
This indication is approved under accelerated approval based on reduction of proteinuria. It has not been established whether VOYXACT slows kidney function decline over the long-term in patients with IgAN. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory clinical trial.
IMPORTANT SAFETY INFORMATION
CONTRAINDICATION
VOYXACT is contraindicated in patients with serious hypersensitivity to sibeprenlimab-szsi or any of the excipients of VOYXACT.
WARNINGS AND PRECAUTIONS
Immunosuppression and Increased Risk of Infections: VOYXACT suppresses the immune system by reducing antibody production, which may increase the risk of infections. Patients with chronic or recurring infections may have an increased risk of serious infection. In clinical trials, infections occurred in 49% of patients treated with VOYXACT compared with 45% of patients treated with placebo.
Before initiating VOYXACT, assess patients for active infections. During treatment, monitor patients for signs and symptoms of infection. If a serious infection develops, consider interrupting VOYXACT until the infection is controlled.
Immunosuppression and Immunization Risks: Because of its mechanism of action, VOYXACT may interfere with immune responses to vaccines and increase the risk of infection from live vaccines. Live vaccines are not recommended within 30 days prior to initiation of VOYXACT or during treatment with VOYXACT as safety has not been established. No data are available on the secondary transmission of infection from persons receiving live vaccines to patients receiving VOYXACT or on the efficacy of immunizations administered while receiving VOYXACT.
Common Adverse Reactions: The most common adverse reactions (reported in ≥10% of patients treated with VOYXACT and at a higher incidence than placebo) in patients treated with VOYXACT and placebo, respectively, were infections (49% versus 45%) and injection site reactions (24% versus 23%). The most common infection was upper respiratory infection (15% versus 14%), and the most common injection site reaction was injection site erythema (13% versus 12%). Most adverse reactions were reported as mild or moderate in severity and resolved without treatment interruption or discontinuation.
Pregnancy: There are no available data on VOYXACT use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. Monoclonal antibodies, such as sibeprenlimab-szsi, can be actively transported across the placenta as pregnancy progresses; therefore, potential effects on a fetus are likely to be greater during the second and third trimester of pregnancy.
Lactation: There are no data on the presence of sibeprenlimab-szsi in human milk, the effects of sibeprenlimab-szsi on the breastfed infant, or the effects of sibeprenlimab-szsi on milk production.
Pediatric Use: Safety and effectiveness of VOYXACT in pediatric patients have not been established.
Geriatric Use: Clinical studies of VOYXACT did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger adult patients.
Pregnant women exposed to VOYXACT, or their healthcare providers, should report VOYXACT exposure by calling 1-833-869-9228 or visiting www.VOYXACT.com
To report SUSPECTED ADVERSE REACTIONS, contact Otsuka America Pharmaceutical, Inc. at 1-800-438-9927 or FDA at 1-800-FDA-1088 (www.fda.gov/medwatch).
Please see FULL PRESCRIBING INFORMATION and PATIENT INFORMATION
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.
Otsuka America Pharmaceutical, Inc. and Otsuka Pharmaceutical Development & Commercialization, Inc. are the US-based indirect subsidiaries of the global healthcare company Otsuka Pharmaceutical Co. Ltd. Otsuka’s US companies share a deep commitment to the development and commercialization of innovative products in the spaces of neuroscience, nephrology, and immunology. At our core is perseverance—a fierce determination to overcome any obstacle, regardless of setbacks, on behalf of patients, caregivers, and their loved ones. We will not be bound by doing what’s been done before. Learn more at www.otsuka-us.com.
References
- Hitoshi Suzuki, Vivek Jha, Manuel Praga, Michael Walsh, José Suassana, Fernando Nolasco, Yoram Yagil, Kenar D. Jhaveri, Raphaël Duivenvoorden, Lucia del Vecchio, Russell Villanueva, Lokesh Shah, Jing Xia, Cecile Fajardo, Jeff Hafkin. EFFECT OF SIBEPRENLIMAB ON MICROSCOPIC HEMATURIA IN ADULTS WITH IgA NEPHROPATHY: INTERIM ANALYSIS OF THE “VISIONARY” PHASE 3 TRIAL. World Congress of Nephrology 2026.
- V. Perkovic, H. Trimarchi, V. Tesar, R. Lafayette, M.G. Wong, J. Barratt, Y. Suzuki, A. Liew, H. Zhang, K. Carroll, V. Jha, A. Quevedo, S.H. Han, M. Praga, B. Chacko, M. Sahay, C.K. Cheung, L. Kooienga, M. Walsh, J. Xia, C. Fajardo, L. Shah, J. Hafkin, and D.V. Rizk. Sibeprenlimab in IgA Nephropathy — Interim Analysis of a Phase 3 Trial. The New England Journal of Medicine. 2025. Nejm.org.
- 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/.
- 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.
- Lai K. Iga nephropathy. Nature reviews. Disease primers. 2016
- 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.
- 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.
- Chang S, Li XK. The Role of Immune Modulation in Pathogenesis of IgA Nephropathy (nih.gov)
- 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
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