Otsuka Pharmaceutical Development & Commercialization, Inc. and Otsuka Pharmaceutical Co., Ltd. (Otsuka) today announce the U.S. Food and Drug Administration (FDA) has accepted for review the Biologics License Application (BLA) for sibeprenlimab, an investigational monoclonal antibody that selectively inhibits the activity of APRIL (A PRoliferation-Inducing Ligand) in adults with immunoglobulin A nephropathy (IgAN). APRIL plays a key role in the pathogenesis of IgAN as explained by the 4-hit process, in which pathogenic galactose-deficient IgA (Gd-IgA1) is produced, leading to the synthesis of autoantibodies against Gd-IgA1, immune complex formation, and deposition in the glomerular mesangium. Sibeprenlimab is a single-dose prefilled syringe for subcutaneous injection every four weeks intended for self-administration, providing patients the convenience of at-home delivery.
The BLA is supported by the Phase 3 VISIONARY clinical trial (NCT05248646), which met its primary endpoint at the prespecified interim analysis, and results from the Phase 2 ENVISION clinical trial (NCT04287985). Sibeprenlimab demonstrated a statistically significant and clinically meaningful reduction in 24-hour uPCR after nine months of treatment compared to placebo in the Phase 3 VISIONARY trial.1
The BLA has been granted priority review and a Prescription Drug User Fee Act (PDUFA) target action date of November 28, 2025.
“Over the past decade, Otsuka has consistently approached difficult-to-treat diseases in nephrology with scientific and clinical innovation, seeking to provide crucial advancements for underserved patients with complex conditions like IgA nephropathy,” said John Kraus, M.D., Ph.D., executive vice president and chief medical officer, Otsuka Pharmaceutical Development & Commercialization, Inc. “If approved, sibeprenlimab would enable individuals living with IgA nephropathy to self-inject once every 4 weeks. We are thankful to share a potential treatment that could offer important clinical benefits and convenience to those living with this disease.”
Sibeprenlimab has Breakthrough Therapy designation for the treatment of IgAN based on the favorable results from the Phase 2 (ENVISION) trial (NCT04287985).2
IgAN is a progressive, autoimmune, chronic kidney disease that can lead to end-stage kidney disease (ESKD) over the lifetime of most patients under current optimized standard care.3
Targeting APRIL represents a potential therapeutic strategy to disrupt IgAN’s pathogenesis via the 4-hit process, which may reduce production of immune complexes, which can deposit into kidney tissue, and may lead to ESKD and the need for transplantation.1,2,4,5
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 and plays a key role in the 4-hit process. By binding and inhibiting APRIL, sibeprenlimab may help reduce the amount of immunoglobulin A (IgA) and Gd-IgA1 levels. Lower levels of Gd-IgA1 provide less substrate for immune complex formation, and may also result in reduced auto-antibody production. Decreased immune complex creation should result in diminished deposition in the kidney, and reduced proteinuria and kidney inflammation. By reducing the production of Gd-IgA1, sibeprenlimab may help slow kidney damage and progression toward ESKD.2,4,5,6 By inhibiting APRIL, sibeprenlimab may help address one of the IgAN-specific drivers for nephron loss.
About IgAN and APRIL
IgAN is a progressive, autoimmune, chronic kidney disease that typically manifests in adults aged 20-40 years and leads to ESKD over the lifetime of most patients.3,6,7
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.6 Despite supportive care, there is an unmet need for treatments that address the root cause of the condition. Continued research in the disease remains crucial to uncovering opportunities for advancement in our understanding and treatment of patients.8
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 produce IgA, particularly the pathogenic Gd-IgA1 that forms immune complexes in the kidneys.8
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, renal, 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/.
References
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