Sibeprenlimab Receives U.S. FDA Breakthrough Therapy Designation for the Treatment of Immunoglobulin A Nephropathy ( IgAN )

PRINCETON, N.J. & TOKYO & WALTHAM, Mass. — Otsuka Pharmaceutical Development & Commercialization, Inc., (OPDC); Otsuka Pharmaceutical, Co. Ltd. (Otsuka); and Visterra, Inc., an Otsuka group company announce that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation for the investigational drug sibeprenlimab for the treatment of immunoglobulin A nephropathy (IgAN; Berger’s disease).

Sibeprenlimab is a humanized monoclonal antibody that blocks the action of the B-cell growth factor, APRIL (an acronym for a proliferation-inducing ligand), which plays a key role in the development and progression of IgAN. Otsuka and Visterra announced positive results of the Phase 2 ENVISION trial (NCT04287985) for IgAN in November 2023. The trial results were also published in The New England Journal of Medicine. Breakthrough therapy designation is granted by the FDA for a drug intended to treat a serious condition when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on at least one clinically significant endpoint. Breakthrough therapy designation allows the agency to prioritize and focus resources on the most promising products for which no satisfactory treatment option exists.

“We are encouraged by the FDA’s decision to grant breakthrough therapy status for the sibeprenlimab program,” said John Kraus, M.D., Ph.D., executive vice president and chief medical officer at Otsuka. “This is an important milestone that recognizes the potential value that this investigational candidate may have in the future for people living with one of the most common causes of kidney failure. Otsuka and Visterra are committed to advancing the Phase 3 trial for sibeprenlimab and we are deeply appreciative to all of the study participants, their caregivers, and the investigators who have contributed so much to this research.”

Immunoglobulin A nephropathy is the most common form of primary glomerulonephritis worldwide and is the most common cause of kidney failure in young adults. The disease is associated with a reduction in life expectancy of 10 years, with at least 30 percent of affected patients progressing to kidney failure within 20 to 30 years, despite optimized standard of care therapy. Current standard of care management is based on renin-angiotensin aldosterone system (RAAS) blockers and adequate blood pressure control, but the risk of kidney failure remains high.

“Sibeprenlimab is the first of several precision therapy biologics designed and engineered by Visterra to treat chronic kidney disease patients with major unmet medical needs,” said Brian J. G. Pereira, M.D., chief executive officer of Visterra Inc. “The results of the Phase 2 trial in patients with IgA nephropathy have been encouraging, and we look forward to completion of the Phase 3 trial and submission of the Biological Licensing Application (BLA) to the US FDA and other global regulatory authorities.”

 

About Sibeprenlimab

Sibeprenlimab (formerly VIS649) is an investigational humanized IgG2 monoclonal antibody that reduces the production of Gd-IgA1 by binding to a specific signaling molecule called APRIL (short for “a proliferation-inducing ligand”), which has been demonstrated to be a driver of IgA and Gd-IgA1 production. By binding and neutralizing APRIL, sibeprenlimab may reduce the amount of IgA and Gd-IgA1. Lower levels of Gd-IgA1 may then result in reduced auto-antibody production, which in turn may result in fewer immune complexes, decreased immune complex deposits in kidney, and reduced kidney inflammation. By reducing the production of Gd-IgA1, sibeprenlimab is believed to prevent further kidney damage and the progression to end stage kidney disease.

 

About APRIL (A Proliferation-Inducing Ligand)

APRIL is a tumor necrosis factor (TNF) superfamily cytokine involved in B-cell signaling. Its function in driving IgA class switch recombination and production and survival of IgA-secreting plasma cells has become increasingly acknowledged as a cytokine likely to play a key role in pathogenesis of IgAN.

 

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’ 2,000 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 Company, Ltd., which is a subsidiary of Otsuka Holdings Co., Ltd. headquartered in Tokyo, Japan. The Otsuka group of companies employed 47,000 people worldwide and had consolidated sales of approximately USD 13.1 billion in 2022.

 

About Visterra, Inc.

Visterra is a clinical-stage biotechnology company and a wholly owned subsidiary of Otsuka America, Inc. committed to developing innovative antibody-based therapies for the treatment of patients with kidney diseases and other hard-to-treat autoimmune diseases.

Visterra’s 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 IgA nephropathy and other kidney diseases, immunologically-driven diseases and infectious diseases.