Otsuka Presents Landmark Final Phase 3 VISIONARY Results at ASN Demonstrating VOYXACT® (sibeprenlimab-szsi) Stabilized Kidney Function and Reduced Risk of Disease Progression and Kidney Failure, Redefining Treatment Paradigm in IgA Nephropathy

• Results from the Phase 3 VISIONARY trial showed a 97.1% reduction in the risk of a composite kidney outcome event of kidney function decline or kidney failure in patients treated with VOYXACT compared with placebo over two years.
• VISIONARY demonstrated sustained preservation of kidney function across all prespecified subgroups over two years, supporting the findings previously reported in the entire study population and confirming the role of selective APRIL inhibition as a disease-modifying treatment in IgAN.
• Overall VOYXACT was safe and well tolerated over two years as compared to placebo, suggesting that it has a favorable clinical profile for therapeutic use.
• Final results were published today in The New England Journal of Medicine.
• Otsuka successfully completed rolling submission of a supplemental Biologics License Application (sBLA) to the U.S. FDA for traditional approval of VOYXACT.

PRINCETON, N.J. & TOKYO--(BUSINESS WIRE)--Otsuka Pharmaceutical Development & Commercialization, Inc. and Otsuka Pharmaceutical Co., Ltd. (Otsuka) today announced the final two-year results from the Phase 3 VISIONARY study demonstrating sustained preservation of kidney function with VOYXACT^® (sibeprenlimab-szsi) in adults with primary immunoglobulin A nephropathy (IgAN) at risk for disease progression. Treatment with VOYXACT stabilized kidney function and reduced the risk of a composite kidney outcome event of kidney function decline or kidney failure compared with placebo by 97.1%, translating to meaningful clinical outcomes in adults with primary IgAN at risk for disease progression. With the largest patient population evaluated through two years in a placebo-controlled trial, VISIONARY provides a substantial and robust body of evidence and is the first Phase 3 IgAN study to achieve the 2025 KDIGO treatment goal of slowing kidney function decline to near-physiologic rates (<1 mL/min/1.73 m²/year for most adults), effectively halting disease progression¹. These findings further support selective APRIL inhibition as a disease-modifying therapeutic approach targeting a key driver of IgAN pathogenesis without broader immune suppression^2,3,4. At two years, overall safety remained favorable for VOYXACT compared to placebo, with similar rates of adverse events, including infections and injection site reactions between the treatment groups. These data were presented today at American Society of Nephrology (ASN) Kidney Week 2026 in Denver, Colorado, as a featured oral presentation during the Opening Plenary Session, as a late-breaking poster presentation, and within the ASN press program. These findings were published simultaneously today in The New England Journal of Medicine.

“For patients with IgA nephropathy, preserving kidney function and preventing kidney failure are the outcomes that matter most,” said Dana Rizk, M.D., professor of medicine in the Division of Nephrology at the University of Alabama at Birmingham, VISIONARY study site principal investigator and co-chair of the steering committee. “In the largest Phase 3 IgA nephropathy dataset reported to date, VISIONARY demonstrated sustained kidney function stabilization over two years, aligning with the KDIGO eGFR treatment goals. The trial also showed a 97.1% reduction in the risk of kidney failure events. For clinicians, the consistency and magnitude of these results provide compelling evidence that sibeprenlimab delivers a significant treatment effect. These findings suggest that selective APRIL inhibition has the potential to change the long-term trajectory of IgA nephropathy and redefine what may be possible for patients living with this progressive disease.”

Among 510 randomized patients, progression to the composite kidney function outcome occurred in 1 of 259 patients receiving VOYXACT (0.4%) compared with 28 of 251 patients receiving placebo (11.2%), representing a 97.1% lower hazard of a composite kidney outcome. Individual components of the composite kidney outcome consistently favored sibeprenlimab. Compared with placebo, fewer patients receiving sibeprenlimab experienced a sustained eGFR decline of at least 40% (1 vs 28), sustained doubling of serum creatinine (0 vs 13), or sustained eGFR below 15 mL/min/1.73 m² (1 vs 10). No patients receiving sibeprenlimab initiated kidney replacement therapy, compared with 5 receiving placebo. VOYXACT also produced sustained reductions in proteinuria, with a 61.3% reduction in 24-hour uPCR at Month 24 and was associated with hematuria resolution (negative dipstick) in 78.6% of patients with baseline hematuria versus 20.2% with placebo.

The overall safety profile of VOYXACT remained consistent through two years and was comparable to placebo, with similar rates of overall adverse events (90.7% vs 90.0%), infections and infestations (51.4% vs 51.0%), and injection site reactions (35.1% vs 32.3%). No new safety signals were identified, and rates of serious infections were lower with VOYXACT than placebo (1.9% vs 4.0%), alongside lower rates of serious and severe adverse events and treatment discontinuations.

“The VISIONARY results redefine what may be possible for people living with IgA nephropathy,” said John Kraus, M.D., Ph.D., executive vice president and chief medical officer, Otsuka. “VOYXACT delivered durable stabilization of kidney function and substantially reduced the risk of kidney failure events, with a safety profile comparable to placebo over two years. Such magnitude and durability of the Kaplan-Meier curve separation rarely seen in kidney outcome trials, positive eGFR slope and achievement of the 2025 KDIGO treatment goal for near-physiologic kidney function decline provide conclusive evidence that disease-modification with selective APRIL inhibition preserves kidney function. Together with the simultaneous publication in The New England Journal of Medicine, these findings reinforce APRIL as a fundamental driver of IgAN and signal a potential shift in how the disease is treated.”

As presented by Dr. Rizk at the GlomCon Hawaii 2026 conference in August 2026, VISIONARY met its key secondary endpoint highlighting a positive, annualized eGFR slope of +0.3 (95% CI, -0.4 to 0.9) mL/min/1.73 m²/year with VOYXACT versus -4.2 (95% CI, -4.9 to -3.6) mL/min/1.73 m²/year with placebo, demonstrating a statistically significant treatment effect of +4.5 (95% CI, 3.6 to 5.4; p<0.0001) mL/min/1.73 m²/year at two years. The treatment effect of VOYXACT was consistent across prespecified stratification factors including screening uPCR-24h, eGFR, and SGLT2i use, supporting broad therapeutic applicability in patients with IgAN. At two years, the least square mean change from baseline in eGFR showed +1.3 mL/min/1.73 m² with VOYXACT (95% CI, −0.3 to 2.8), compared with −7.9 mL/min/1.73 m² with placebo (95% CI, −9.5 to −6.4), resulting in a relative group treatment difference of +9.2 mL/min/1.73 m² (95% CI, 7.1 to 11.4; p<0.0001) demonstrating preservation of kidney function with VOYXACT.

Taken together, these investigational data support selective APRIL inhibition as a potential disease-modifying approach in IgAN. The clinical benefits of VOYXACT were maintained regardless of anti-drug or neutralizing antibody status. Further, the benefit-risk profile observed demonstrates that selective APRIL inhibition and reductions in immunoglobulin levels were maintained without an observed increase in infection risk or the emergence of new safety concerns over two years.

Otsuka would like to thank the patients, families, advocates, and investigators who participated in the VISIONARY study and whose commitment and perseverance made this research possible.

About the VISIONARY Study
VISIONARY (NCT05248646) is a global, randomized, double-blind, placebo-controlled Phase 3 study evaluating the efficacy and safety of VOYXACT (sibeprenlimab-szsi) in adults with primary IgAN at risk for disease progression. The primary efficacy endpoint assessed proteinuria reduction, as measured by the change in 24-hour urine protein-to-creatinine ratio (uPCR-24h) from baseline compared with placebo after nine months of treatment. The key secondary endpoint evaluated annualized eGFR slope over two years, providing an assessment of kidney function over time. The least square mean change from baseline in eGFR at month 24 was also evaluated as a secondary endpoint, offering a complementary measure of overall treatment effect at a defined timepoint^1,2. This program continues to advance the science in IgAN, with future data forthcoming in an open-label, long-term extension study (NCT05248659).

About IgAN
IgA nephropathy (IgAN) is a progressive, immune-mediated, chronic kidney disease that typically manifests in adults aged 20-40 years and can lead to kidney failure (KF) over the lifetime of most patients^5-7. IgAN is characterized by the accumulation of Gd-IgA1 complexes in the kidneys⁸. IgAN can lead to progressive loss of kidney function and, eventually, KF, imposing a significant burden on patients⁷. Despite supportive care, there is an unmet need for treatments that address the root causes of the condition⁸. Continued research in IgAN remains crucial to uncovering opportunities for advancement in our understanding and treatment of patients⁸.

About VOYXACT® (sibeprenlimab-szsi)
VOYXACT (sibeprenlimab-szsi) 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)^2,8,9. 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 once every four weeks. VOYXACT is the first-and-only U.S. FDA-approved treatment for adults with primary IgAN at risk for disease progression that selectively inhibits APRIL, a key immune driver of the disease², and the only selective APRIL inhibitor shown to stabilize eGFR versus placebo over two years. VOYXACT was granted accelerated approval by the U.S. FDA on November 25, 2025. Otsuka has completed the rolling submission of an sBLA to the U.S. FDA for VOYXACT traditional approval, which will include the two-year eGFR findings. Recently a Phase 3, open-label clinical trial (NCT07770815) evaluating sibeprenlimab administered subcutaneously every four weeks in pediatric participants aged 2 to 17 years with IgAN, as an add-on to standard-of-care therapy was initiated. Additionally, a Phase 2, multicenter, open-label trial (NCT07861113) to evaluate the efficacy and safety of sibeprenlimab in primary membranous nephropathy (pMN), immune-mediated focal segmental glomerulosclerosis (IM-FSGS), and minimal change disease (MCD) was also initiated.

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

1. Kidney Disease: Improving Global Outcomes (KDIGO) IgAN and IgAV Work Group. KDIGO 2025 Clinical Practice Guideline for the Management of Immunoglobulin A Nephropathy (IgAN) and Immunoglobulin A Vasculitis (IgAV). Kidney Int. 2025;108(4S):S1-S71.
2. Perkovic, V., Trimarchi, H., Tesar, V., Lafayette, R., Wong, M. G., Barratt, J., Suzuki, Y., Liew, A., Zhang, H., Carroll, K., Jha, V., Quevedo, A., Han, S. H., Praga, M., Chacko, B., Sahay, M., Cheung, C. K., Kooienga, L., Walsh, M., … Rizk, D. V. (2026). Sibeprenlimab in IGA nephropathy — interim analysis of a phase 3 trial. New England Journal of Medicine, 394(7), 635–646. https://doi.org/10.1056/nejmoa2512133
3. Hitoshi Suzuki, et. al. WCN26-6808 EFFECT OF SIBEPRENLIMAB ON MICROSCOPIC HEMATURIA IN ADULTS WITH IgA NEPHROPATHY: INTERIM ANALYSIS OF THE “VISIONARY” PHASE 3 TRIAL, Kidney International Reports, Volume 11, Issue 4, Supplement, 2026, 106279, ISSN 24680249, https://doi.org/10.1016/j.ekir.2026.106279.
4. 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
5. 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/.
6. 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.
7. Lai K. Iga nephropathy. Nature reviews. Disease primers. 2016
8. 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.
9. Chang S, Li XK. The Role of Immune Modulation in Pathogenesis of IgA Nephropathy (nih.gov)