Sibeprenlimab

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.libproxy1.nus.edu.sg/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.

The sibeprenlimab Phase 2 clinical trial results will also be presented this week at the American Society of Nephrology (ASN) Kidney Week.1 Findings demonstrated that 12 months of sibeprenlimab treatment resulted in significant reductions in proteinuria (protein in urine), a marker of kidney damage compared to placebo in patients with IgAN.1 IgAN, also known as Berger’s disease, is the most common cause of kidney failure in young adults2 and is associated with a 10-year reduction in life expectancy.3 PRINCETON, N.J. & WALTHAM, Mass.--(BUSINESS WIRE)-- Otsuka Pharmaceutical Development & Commercialization, Inc. and Visterra Inc., today announced that the full results of a Phase 2 trial of sibeprenlimab (VIS649) for treatment of immunoglobulin A nephropathy (IgAN; Berger’s disease) have been published in the New England Journal of Medicine.1 The topline findings will also be presented in a late-breaking poster session at the American Society of Nephrology (ASN) Kidney Week meeting in Philadelphia, PA. This press release features multimedia. View the full release here: Sibeprenlimab is an investigational humanized monoclonal antibody that blocks the action of the cytokine A Proliferation Inducing Ligand (APRIL), an immune cell growth factor believed to play a key role in the development and progression of IgAN.1,4,5 The Phase 2 trial randomized 155 adult participants with biopsy-confirmed IgAN to monthly intravenous injections of sibeprenlimab 2, 4, or 8 mg/kg, or placebo for 12 months. The primary outcome measure was the change from baseline in 24-hour urine protein-to-creatinine ratio (uPCR) at month 12. Secondary outcomes included safety and change in estimated glomerular filtration rate (eGFR), a measure of kidney function.1 The study results demonstrated that 12 months of sibeprenlimab treatment in patients with IgAN resulted in significant reductions in proteinuria compared to placebo. At 12 months, geometric mean ratio reduction in 24-hour uPCR from baseline was 47.2%, 58.8%, 62.0%, and 20.0% with sibeprenlimab 2, 4, and 8 mg/kg, and placebo, respectively.1 Beneficial changes in eGFR were also observed in the sibeprenlimab groups compared to placebo. The annual eGFR change was −2.7, +0.2, −1.5, and −7.4 ml/1.73 m2 with sibeprenlimab 2, 4, and 8 mg/kg, and placebo, respectively. This reflects a stabilization of eGFR with sibeprenlimab compared to the eGFR decline observed with placebo.1 The incidence of treatment-emergent adverse events (TEAEs) for patients on sibeprenlimab and placebo was similar. The safety pro sibeprenlimab showed no evidence of undesirable toxicity or clinically meaningful immunosuppression during this trial and follow-up through month 16.1 “IgAN is the most common form of primary glomerulonephritis and is associated with a significant reduction in life expectancy,” said Brian J. G. Pereira, M.D., CEO of Visterra, Inc., and the senior author of the New England Journal of Medicine paper. “Current therapies have modest efficacy, at best, in reducing the rate of chronic kidney disease progression and new disease-specific targeted treatment options would be hugely beneficial.” “We are excited by these results, which bring us one step closer to addressing the critical unmet treatment needs of patients with this complex, life-threatening condition,” said John Kraus, M.D., Ph.D., executive vice president and chief medical officer, Otsuka Pharmaceutical Development & Commercialization, Inc. "We look forward to continuing to evaluate the potential of sibeprenlimab in the ongoing Phase 3 trial program." About Immunoglobulin A Nephropathy Immunoglobulin A nephropathy (IgAN; Berger’s disease) is the most common form of primary glomerulonephritis worldwide and is the most common cause of kidney failure in young adults.1,2 The disease is associated with a reduction in life expectancy of 10 years,3 with at least 30% 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 About Sibeprenlimab Sibeprenlimab (VIS649) is an investigational humanized immunoglobulin G (IgG2) monoclonal antibody that binds to and blocks the biological actions of the cytokine A PRoliferation Inducing Ligand (APRIL), a key factor in the production of galactose-deficient IgA1 (Gd-IgA1), which has been demonstrated to play a key role in the pathogenesis of IgAN.1,4,5 About the Phase 2 Sibeprenlimab Trial The multicenter, randomized, double-blind, placebo-controlled, multiple-dose, parallel-group study was conducted in adults with biopsy-confirmed IgAN at high risk of disease progression, despite having received standard-of-care treatment. Participants were randomized 1:1:1:1 to intravenous sibeprenlimab 2, 4, or 8 mg/kg or placebo monthly for 12 months.9 The study was designed to test the safety and efficacy of different doses of sibeprenlimab. The main objectives were to evaluate the safety and tolerability of sibeprenlimab and to evaluate the dose response to different doses of sibeprenlimab on proteinuria and eGFR.9 The study was comprised of three main periods, Screening, Treatment (12 months) and Follow-Up (4 months). The findings from this study form the basis for the subsequent clinical development of sibeprenlimab.9 About Otsuka Otsuka Pharmaceutical Co., Ltd. is a global healthcare company with the corporate philosophy of “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 CNS, 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’ 2,000 employees in the U.S. develop and commercialize medicines in the areas of mental health and kidney diseases, 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 and connect with us on LinkedIn and X at @OtsukaUS. Otsuka Pharmaceutical Co., Ltd.’s global website is accessible at About Visterra Visterra is a clinical-stage biotechnology company and a wholly owned subsidiary of Otsuka America Pharmaceutical, Inc. committed to developing innovative antibody-based therapies for the treatment of patients with kidney diseases and other hard-to-treat autoimmune 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 IgA nephropathy and other kidney diseases, immunologically-driven diseases and infectious diseases. Prior to its acquisition by Otsuka, Visterra was funded by investments by Polaris Partners, Flagship Pioneering, the Bill and Melinda Gates Foundation, MRL Ventures Fund, Vertex Ventures HC, Serum Institute of India Private Ltd., Temasek Holdings, Omega Funds, Cycad Group, Lux Capital, Alleghany Financial Group Ventures, CTI Life Sciences Fund and Alexandria Equities. For more information, visit . References 1. Mathur M, Barratt J, Chacko B, et al. A Phase 2 Trial of Sibeprenlimab in Immunoglobulin A Nephropathy Patients. NEJM. 2023 2. Floege J, Amann K. Primary glomerulonephritides. Lancet. 2016;387(10032):2036-2048. 3. 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. 4. 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. 5. Chang S, Li XK. The Role of Immune Modulation in Pathogenesis of IgA Nephropathy. Front Med (Lausanne). 2020;7:92. 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. Rizk DA, Perkovic V, Lafayette R, et al. A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Sibeprenlimab Administered Subcutaneously in Patients With IgAN. Presented at the ASN Kidney Week 2022, November 3–6, 2022, Orlando, FL. 9. ClinicalTrials.gov. National Library of Medicine (U.S.). Safety and Efficacy Study of VIS649 for IgA Nephropathy Identifier: NCT04287985. .