Otsuka Receives FDA Accelerated Approval for VOYXACT® (sibeprenlimab-szsi) for the Reduction of Proteinuria in Adults with Primary Immunoglobulin A Nephropathy (IgAN) at Risk for Disease Progression

• VOYXACT achieved a significant placebo-adjusted treatment effect of 51% (P<0.0001) reduction in proteinuria at 9 months of treatment (-50% VOYXACT vs 2% placebo) in the VISIONARY Phase 3 interim analysis.
• In the study, the most common adverse reactions (reported in ≥10% of patients treated with VOYXACT and at a higher incidence than placebo) reported in patients treated with VOYXACT and placebo, respectively, were infections (49% versus 45%) and injection site reactions (24% versus 23%).
• VOYXACT blocks A-PRoliferation-Inducing-Ligand (APRIL), resulting in reduced levels of serum galactose-deficient IgA1 (Gd-IgA1). Gd-IgA1 is implicated in the pathogenesis of IgAN.
• Proteinuria reduction is a recognized surrogate marker correlating with delaying progression to kidney failure and has been used as a surrogate endpoint in IgAN clinical trials to support accelerated regulatory approvals.
• VOYXACT is a self-administered, subcutaneous injection dosed every 4 weeks.
• Despite the current standard of care, IgAN is a progressive, immune-mediated, chronic kidney disease that typically manifests in adults aged 20-40 years and can lead to end-stage kidney disease (ESKD) over the lifetime of most patients.

Otsuka Pharmaceutical Development & Commercialization, Inc. and Otsuka Pharmaceutical, Co. Ltd. (Otsuka) today announce the U.S. Food and Drug Administration (FDA) has granted accelerated approval of VOYXACT (sibeprenlimab-szsi) for the reduction of proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk for disease progression. VOYXACT is a self-administered, subcutaneous injection dosed every four weeks. VOYXACT was granted accelerated approval based on the VISIONARY Phase 3 interim analysis, where it achieved a significant placebo-adjusted treatment effect of 51% (P<0.0001) reduction in proteinuria at nine months (n=320) of treatment (-50% VOYXACT vs 2% placebo). VOYXACT is the first and only therapy to block A-PRoliferation-Inducing-Ligand (APRIL).

Proteinuria reduction is a recognized surrogate marker correlating with delaying progression to kidney failure and has been used as a surrogate endpoint in IgAN clinical trials to support accelerated regulatory approvals¹. This indication is approved by the FDA under the accelerated approval pathway 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 from the ongoing Phase 3 VISIONARY study evaluating whether VOYXACT slows disease progression as measured by estimated glomerular filtration rate (eGFR) decline at 24 months. The eGFR data are expected in early 2026 and are intended to support traditional FDA approval.

“The availability of VOYXACT represents a novel targeted approach to help manage this complex disease for patients living with IgAN,” said John Kraus, M.D., Ph.D., executive vice president and chief medical officer, Otsuka. “With its targeted mechanism, strong efficacy, safety profile, and once-every-four-weeks dosing, VOYXACT offers a new option for IgAN patients. We recognize the urgent need for new treatment options for IgAN and are thankful for the patients and healthcare professionals who continue to participate in our clinical trial program.”

VOYXACT works by blocking 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)^2,3,4,5. Inhibition of APRIL results in reduced levels of serum galactose-deficient IgA1 (Gd-IgA1), which is implicated in the pathogenesis of IgAN.

“VOYXACT is the first approved treatment for adults with primary IgAN at risk for disease progression that blocks the activity of APRIL,” said Dr. Dana Rizk, professor of medicine in the division of nephrology at the University of Alabama at Birmingham and VOYXACT VISIONARY study investigator and co-chair of the steering committee. “I'm encouraged by its potential to help improve the outlook for IgAN patients.”

“We’re thrilled to hear the news about the accelerated approval of VOYXACT,” said Bonnie and Ed Schneider, IgA Nephropathy Foundation co-founders. “It’s important for patients who are managing IgAN to have new treatment options. On behalf of our board of directors, leadership, and the community we serve, thank you to the patients and experts involved in helping advance this option.” Otsuka is honored to support the IgAN Foundation and other organizations in raising awareness of IgA Nephropathy.

Data Supporting Approval

The Phase 3 VISIONARY study is a multicenter, randomized, double-blind, placebo-controlled trial consisting of 510 adult patients with IgAN who were receiving standard-of-care therapy (defined as maximally tolerated ACE inhibitor and/or ARB with or without SGLT2 inhibitor), designed to evaluate the efficacy and safety of sibeprenlimab 400 mg administered subcutaneously every four weeks, compared to placebo⁶.

In the trial, patients had to have a biopsy-confirmed IgAN diagnosis, urine protein-to-creatinine ratio (uPCR)≥ 0.75 g/g or urine protein ≥ 1.0g/day, eGFR≥ 30 mL/min/1.73 m², and be on a stable dose of supportive therapy (ACE inhibitor and/or ARB with or without SGLT2 inhibitor) for ≥ three months prior to screening⁶. Patients were randomized to treatment once every four weeks with VOYXACT or placebo and remained on supportive therapy throughout the study⁶.

The primary endpoint is the ratio of 24-hour uPCR at month nine compared with baseline. In the VISIONARY Phase 3 interim analysis (n=320), VOYXACT achieved a significant placebo-adjusted treatment effect of 51% (P<0.0001) reduction in proteinuria at nine months of treatment (-50% VOYXACT vs 2% placebo). Proteinuria reduction is a recognized surrogate marker correlating with delaying progression to kidney failure and has been used as a surrogate endpoint in IgAN clinical trials to support accelerated regulatory approvals¹. The study is still ongoing, and the secondary endpoint data of the annualized slope of eGFR over 24 months is expected to be available in 2026.

In the study, 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.

About IgAN

IgAN is a progressive, immune-mediated, chronic kidney disease that typically manifests in adults aged 20-40 years and can lead to end-stage kidney disease (ESKD) over the lifetime of most patients^7,8,9. 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 patients⁸. Despite supportive care, there is an unmet need for treatments that address the root causes of the condition⁴. Continued research in the disease remains crucial to uncovering opportunities for advancement in our understanding and treatment of patients⁴.

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 (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)^2,5. 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 global healthcare company with the corporate philosophy: Otsuka–people creating new products for better health worldwide. Otsuka researches, develops, manufactures, and markets innovative products, with a focus on pharmaceutical products to meet unmet medical needs and nutraceutical products for the maintenance of everyday health.

In pharmaceuticals, Otsuka is a leader in the challenging areas of mental, kidney, and cardiovascular health and has additional research programs in oncology and on several under-addressed diseases including tuberculosis, a significant global public health issue. These commitments illustrate how Otsuka is a “big venture” company at heart, applying a youthful spirit of creativity in everything it does.

Otsuka established a presence in the U.S. in 1973 and today its U.S. affiliates include Otsuka Pharmaceutical Development & Commercialization, Inc. (OPDC) and Otsuka America Pharmaceutical, Inc. (OAPI). These two companies’ 2,250 employees in the U.S. develop and commercialize medicines in the areas of mental health and nephrology, using cutting-edge technology to address unmet healthcare needs.

OPDC and OAPI are indirect subsidiaries of Otsuka Pharmaceutical Co., Ltd., which is a subsidiary of Otsuka Holdings Co., Ltd. headquartered in Tokyo, Japan. The Otsuka group of companies employed 35,340 people worldwide and had consolidated sales of approximately USD 14.7 billion in 2024.

All Otsuka stories start by taking the road less traveled. Learn more about Otsuka in the U.S. at www.otsuka-us.com and connect with us on LinkedIn and Twitter at @OtsukaUS. Otsuka Pharmaceutical Co., Ltd.’s global website is accessible at https://www.otsuka.co.jp/en/.

About Visterra

Visterra is a biologics research and early-stage clinical development biotechnology company committed to developing innovative antibody-based therapies for the treatment of patients with immune-mediated kidney diseases and other hard-to-treat diseases. Its proprietary Hierotope® platform enables the design and engineering of precision biologics-based product candidates that specifically bind to, and modulate, key disease targets that are not adequately addressed by traditional therapeutic approaches. The platform also includes Fc engineering capabilities for half-life extension, bispecific antibodies, and antibody-drug conjugates (ADCs). Visterra’s pipeline includes programs targeting kidney diseases, immunologically-driven diseases and infectious diseases. Visterra is an indirect subsidiary of Otsuka Pharmaceutical Co., Ltd. For more information, visit www.visterrainc.com.

References

1. 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
2. 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.
3. Chang S, Li XK. The Role of Immune Modulation in Pathogenesis of IgA Nephropathy (nih.gov)
4. 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.
5. 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
6. Perkovic, et al. Evaluating Sibeprenlimab in IgA Nephropathy - Rationale and Baseline Data from the VISIONARY Trial. Kidney International Reports. https://doi.org/10.1016/j.ekir.2025.09.031
7. 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/.
8. Lai K. Iga nephropathy. Nature reviews. Disease primers. 2016
9. 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.

View source version on businesswire.com: https://www.businesswire.com/news/home/20251125491375/en/