Otsuka Files Biologics License Application (BLA) for Sibeprenlimab in the Treatment of Immunoglobulin A Nephropathy

• Phase 3 VISIONARY study met its primary endpoint at the prespecified interim analysis; sibeprenlimab demonstrated a statistically significant and clinically meaningful reduction in 24-hour uPCR after nine months of treatment
• Immunoglobulin A nephropathy 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
• Sibeprenlimab has received Breakthrough Therapy designation from the FDA following favorable results from the Phase 2 (ENVISION) trial (NCT04287985)

Otsuka Pharmaceutical Development & Commercialization, Inc. and Otsuka Pharmaceutical Co., Ltd. (Otsuka) today announce the filing of a Biologics License Application (BLA) with the U.S. Food and Drug Administration (FDA) 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 4-hit process of IgAN pathogenesis and is an important initiating and sustaining factor in IgAN progression by promoting the production of pathogenic Gd-IgA1 and immune complex formation. Sibeprenlimab is a single-dose prefilled syringe for subcutaneous injection every four weeks intended for self-administration or administration by caregiver, providing patients the option of convenience at home.

IgAN is a progressive, autoimmune, chronic kidney disease that is associated with a high risk for progression to end-stage kidney disease (ESKD) over the lifetime of many patients.¹ In 2024, the FDA granted a Breakthrough Therapy designation for sibeprenlimab following favorable results of the Phase 2 ENVISION clinical trial.² This designation accelerates the development and regulatory review of potential new medicines intended to treat a serious condition and address a significant unmet medical need. If approved, sibeprenlimab would be administered via injection every four weeks, which would allow patients the convenience and option of self-administration in the home setting.³

The BLA submission, Otsuka’s first, is supported by results from the Phase 2 ENVISION clinical trial (NCT04287985) and the Phase 3 VISIONARY clinical trial (NCT05248646), which met its primary endpoint by demonstrating that sibeprenlimab produced a statistically significant and clinically meaningful reduction in 24-hour uPCR (urine protein-to-creatine ratio) compared to placebo after nine months of treatment.⁴ In the trial, the safety profile of sibeprenlimab was favorable and consistent with previously reported data.

“This BLA filing marks an important milestone in Otsuka's commitment to address unmet needs in kidney diseases,” said John Kraus, M.D., Ph.D., executive vice president and chief medical officer, Otsuka Pharmaceutical Development & Commercialization, Inc. “Sibeprenlimab’s unique mechanism of action inhibits the activity of APRIL and addresses an IgA-specific driver of kidney loss in IgA nephropathy. APRIL is a cytokine that plays a key role in the pathogenesis of IgA nephropathy and we are optimistic about its potential to be an important treatment option for this progressive kidney disease. On behalf of Otsuka, we are grateful to every patient, caregiver and healthcare professional who has contributed so much to advancing this important research.”

The VISIONARY study is a multicenter, randomized, double-blind, placebo-controlled trial consisting of approximately 530 adult patients (largest trial to date) with IgA nephropathy who were receiving standard-of-care therapy (defined as maximally tolerated ACE inhibitor or ARB +/- SGLT2 inhibitor), designed to evaluate the efficacy and safety of sibeprenlimab 400 mg administered subcutaneously every four weeks, compared to placebo. The primary efficacy endpoint is to evaluate the change in 24-hour uPCR at 9 months compared with baseline.⁴ The secondary endpoint is to evaluate the annualized slope of eGFR estimated over ~24 months.⁴

“This BLA for sibeprenlimab represents a significant achievement in our journey to bring innovative treatments to patients with IgA nephropathy," commented Brian Pereira, M.D., CEO of Visterra, Inc., the U.S. affiliate of Otsuka that designed and engineered sibeprenlimab. “We look forward to the FDA’s review and are grateful for the opportunity to help develop a treatment that could alter the course of this challenging kidney disease and improve patient outcomes.”

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 IgA nephropathy-specific drivers for nephron loss.

About Immunoglobulin A Nephropathy and APRIL

IgA nephropathy 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.^1,7,8

IgA nephropathy is characterized by the accumulation of Gd-IgA1 complexes in the kidneys. IgA nephropathy can lead to progressive loss of kidney function and, eventually, ESKD, imposing a significant burden on patients.⁷ 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.⁹

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

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/.

About Visterra

Visterra is a biologics research and early-stage clinical development biotechnology company and a wholly owned subsidiary of Otsuka America, Inc. 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. For more information, visit www.visterrainc.com.

View source version on businesswire.com: https://www.businesswire.com/news/home/20250331152906/en/