Sibeprenlimab

The treatment is indicated for adult schizophrenia patients who have been stabilised with aripiprazole. Credit: Ground Picture / Shutterstock.com. The European Commission (EC) has approved Otsuka Pharmaceutical Europe and H Lundbeck’s Abilify Maintena 720mg/960mg (aripiprazole) for the maintenance treatment of schizophrenia. The treatment is indicated for use in adult schizophrenia patients who have been stabilised with aripiprazole. The approval marks the introduction of the first once-every-two-month long-acting injectable (LAI) antipsychotic in the European Union (EU) for this indication. Designed for bi-monthly dosing through an intramuscular injection into the gluteal muscle, the new formulation of aripiprazole once every two months LAI is offered in a single-chamber prefilled syringe and does not need reconstitution. The EC’s decision extends to all EU member states, Norway, Iceland and Liechtenstein. See Also: China NMPA accepts Astellas’ sBLA for urothelial cancer treatment EC approves Merck’s KEYTRUDA regimen for NSCLC treatment Otsuka Europe medical affairs vice-president and head Dr Peter Gillberg stated: “We welcome the EC approval of aripiprazole once-every-two-months LAI, which represents a significant milestone in offering adult patients with schizophrenia another simplified treatment regimen. “We hope that this treatment may help to mitigate challenges with adherence, and potentially allow patients and their healthcare practitioners to focus on other elements of care.” The approval was based on the results of a 32-week pharmacokinetic bridging clinical trial. This study also assessed the safety and efficacy of Abilify Maintena as primary and secondary endpoints respectively. The once-every-two-month LAI formulation demonstrated plasma concentrations, effectiveness, safety and tolerability profiles in line with the established once-monthly LAI (Abilify Maintena 400mg) dose in 266 adult subjects, 185 of whom were diagnosed with schizophrenia. Lundbeck research and development executive vice-president and head Dr Johan Luthman stated: “Specifically designed for adult patients with schizophrenia who have been stabilised with aripiprazole, this treatment aims to increase patient adherence and convenience, contributing to the careful and comprehensive management of this chronic condition.” Last month, Otsuka received breakthrough therapy designation for its rare kidney disease drug sibeprenlimab from the US Food and Drug Administration.

PRINCETON, N.J. & TOKYO & WALTHAM, Mass.--( BUSINESS WIRE )--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 pr oliferation- i nducing l igand), which plays a key role in the development and progression of IgAN. 1,2,3 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 . 1 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. 4,5 The disease is associated with a reduction in life expectancy of 10 years, 5 with at least 30 percent of affected patients progressing to kidney failure within 20 to 30 years, despite optimized standard of care therapy. 6,7 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. 8 “ 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 pr oliferation- i nducing l igand”), 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. 1,2,3 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. 2 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. 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, 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. For more information, visit www.visterrainc.com . References 1. 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 2. Chang S, Li XK. The Role of Immune Modulation in Pathogenesis of IgA Nephropathy (nih.gov) 3. 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. 4. Floege J, Amann K. Primary glomerulonephritides. Lancet. 2016;387(10032):2036-2048. 5. Hastings MC, Bursac Z, Julian BA, et al. Life Expectancy for Patients From the Southeastern United States With IgA Nephropathy. Kidney Int Rep. 2017;3(1):99-104. 6. Lai KN, Tang SC, Schena FP, et al. IgA nephropathy. Nat Rev Dis Primers . 2016;2:16001. 7. Gleeson PJ, O'Shaughnessy MM, Barratt J. IgA nephropathy in adults - Treatment Standard [published online ahead of print, 2023 Jul 7]. 8. Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney Int. 2021 Oct;100(4S):S1-S276. doi: 10.1016/j.kint.2021.05.021. PMID: 34556256.