Latest news with #immunoglobulinA
Business Wire
3 days ago
- Business
- Business Wire
Otsuka Sibeprenlimab Phase 3 Data Show a Statistically Significant and Clinically Meaningful Proteinuria Reduction for the Treatment of Immunoglobulin A Nephropathy (IgAN)
PRINCETON, N.J. & TOKYO--(BUSINESS WIRE)--Otsuka Pharmaceutical Development & Commercialization, Inc. and Otsuka Pharmaceutical, Co. Ltd. (Otsuka) today presented results from a pre-specified interim analysis of the Phase 3 VISIONARY study (NCT05248646) evaluating sibeprenlimab, for the treatment of immunoglobulin A nephropathy (IgAN) in adults. Patients treated with sibeprenlimab achieved a 51.2% (P<0.0001) reduction in proteinuria (as measured by 24-hour uPCR [urine protein-to-creatinine ratio]) at nine months of treatment when compared to placebo 1. The data were presented during a late-breaking clinical trials session at the European Renal Association (ERA) Congress in Vienna, Austria. The study, the largest Phase 3 IgAN trial conducted to date, also showed the safety profile of sibeprenlimab was favorable and consistent with previously reported data 1. Specifically, 76.3% of patients treated with sibeprenlimab experienced any Treatment Emergent Adverse Event (TEAE) versus 84.5% in the placebo group. 1 Patients who experienced a serious TEAE were 3.9% treated with sibeprenlimab compared to 5.4% treated with placebo. Sibeprenlimab received Priority Review designation from the FDA last month following its BLA filing in March. Proteinuria reduction is a recognized surrogate marker correlating with delaying progression to kidney failure and has been used as an endpoint in IgAN clinical trials to support accelerated regulatory approvals 2. Sibeprenlimab is an investigational monoclonal antibody that selectively inhibits the activity of APRIL (A PRoliferation-Inducing Ligand) in adults with 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 3,4,5,6. By selectively binding and inhibiting APRIL, sibeprenlimab reduces the amount of immunoglobulin A (IgA) and Gd-IgA1 levels 1. Lower levels of Gd-IgA1 in people with IgAN provide less substrate for immune complex formation 7. Sibeprenlimab is administered in 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. 'We are confident about the potential of sibeprenlimab and are grateful to the patients who are helping to further the science by participating in these important trials,' said John Kraus, M.D., Ph.D., executive vice president and chief medical officer, Otsuka Pharmaceutical Development & Commercialization, Inc. 'Proteinuria control is an important independent predictor for long-term prognosis, and this interim data reinforces our belief that selectively targeting APRIL has the potential to be an effective and safe approach for this progressive and irreversible kidney disease.' The VISIONARY study continues in a blinded manner to evaluate the change in kidney function over 24 months as measured by estimated glomerular filtration rate (eGFR) and is expected to be completed in early 2026. Further prespecified and exploratory analyses of the data will be conducted to determine the full potential of sibeprenlimab for the treatment of IgAN 1. 'The VISIONARY Phase 3 interim analysis shows a robust proteinuria reduction of 51.2% in the group treated with sibeprenlimab relative to placebo. These results affirm our belief in the efficacy of sibeprenlimab in the largest Phase 3 IgAN trial to date. The study enrolled a diverse patient population reflective of the disease epidemiology,' said Dr. Dana Rizk, professor of medicine in the division of nephrology at the University of Alabama at Birmingham. 'The safety data emerging from VISIONARY is reassuring and adds to our existing knowledge about sibeprenlimab's safety profile from prior programs. This is very exciting news for patients and adds a therapeutic option with a novel mechanism of action potentially targeting the immunologic pathogenesis of IgAN.' About the VISIONARY Study The VISIONARY study is the largest IgAN trial to date, and is a multicenter, randomized, double-blind, placebo-controlled trial consisting of approximately 510 adult patients with IgAN 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 1. The primary efficacy endpoint is to evaluate the change in 24-hour uPCR at 9 months compared with baseline. The secondary endpoint is to evaluate the annualized slope of eGFR estimated over ~24 months 1. 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 selectively binding and inhibiting APRIL, sibeprenlimab reduces the amount of immunoglobulin A (IgA) and Gd-IgA1 levels 1. Lower levels of Gd-IgA1 in people with IgAN provide less substrate for immune complex formation 7. Decreased immune complex formation should result in diminished deposition in the kidney, and reduced proteinuria and kidney inflammation 8. By reducing the production of Gd-IgA1, sibeprenlimab may help slow kidney damage and progression toward ESKD 3,4,5,6. By inhibiting APRIL, sibeprenlimab may help address one of the IgAN-specific drivers for nephron loss. About IgAN and APRIL IgAN is a progressive, immune-mediated, chronic kidney disease that typically manifests in adults aged 20-40 years and leads to ESKD over the lifetime of most patients 9,10,11. 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 10. Despite supportive care, there is an unmet need for treatments that address the root causes of the condition. Continued research in the disease remains crucial to uncovering opportunities for advancement in our understanding and treatment of patients 5. 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 galactose-deficient IgA1 (Gd-IgA1) that forms immune complexes in the kidneys 5. 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 and connect with us on LinkedIn and Twitter at @OtsukaUS. Otsuka Pharmaceutical Co., Ltd.'s global website is accessible at About Visterra Visterra is a biologics research and early-stage clinical development biotechnology company 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. Visterra is an indirect subsidiary of Otsuka Pharmaceutical Co., Ltd. For more information, visit References Otsuka Pharmaceutical Development & Commercialization, Study: Phase 3 Trial of Sibeprenlimab in Immunoglobulin A Nephropathy (IgAN). Thompson A, Carroll K, Inker LA, et al. Proteinuria Reduction as a Surrogate End Pointin Trials of IgA Nephropathy. Clin J Am Soc Nephrol. 2019;14(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. Chang S, Li XK. The Role of Immune Modulation in Pathogenesis of IgA Nephropathy ( Cheung CK, Barratt J, Liew A, Zhang H, Tesar V, Lafayette R. The role of BAFF and April in IGA nephropathy: Pathogenic mechanisms and targeted therapies. Frontiers in nephrology. February 1, 2024. Mathur M, Barratt J, Chacko B, et al. A Phase 2 Trial of Sibeprenlimab in Immunoglobulin A Nephropathy Patients. NEJM. 2023 Gharavi, Ali G, et al. 'Aberrant Iga1 Glycosylation Is Inherited in Familial and Sporadic IGA Nephropathy.' Journal of the American Society of Nephrology : JASN, U.S. National Library of Medicine, May 2008, Kant, Sam, et al. 'Advances in Understanding of Pathogenesis and Treatment of Immune-Mediated Kidney Disease: A Review - American Journal of Kidney Diseases.' American Journal of Kidney Diseases, Apr. 2022, Pitcher, D. Braddon, et. al Long-term outcomes in IGA nephropathy. Clinical journal of the American Society of Nephrology : CJASN. Lai K. Iga nephropathy. Nature reviews. Disease primers. 2016 Cheung, Chee Kay & Boyd, JKF & Feehally, J.. (2012). Evaluation and management of IgA nephropathy. Clinical Medicine. 12. s27-s30. 10.7861/clinmedicine.12-6-s27.
Yahoo
28-04-2025
- Health
- Yahoo
Purespring Therapeutics granted European Medicines Agency (EMA) orphan drug designation for PS-002 for the treatment of patients with primary IgA nephropathy (IgAN)
Purespring Therapeutics EMA designation provides orphan status to medicines being developed for rare conditions that are intended for the diagnosis, prevention or treatment of diseases affecting fewer than 5 in 10,000 people in the European Union Purespring has previously demonstrated the potential of PS-002, the Company's lead programme, as an important novel targeted treatment for primary IgAN PS-002 is progressing towards a Phase I/II clinical trial, supported by a strong preclinical data package London – 28 April 2025 - Purespring Therapeutics, a pioneering company focused on transforming the treatment of kidney diseases, today announces that the European Medicines Agency (EMA) has granted orphan drug designation to PS-002, Purespring's lead programme, in IgA nephropathy (IgAN). Orphan drug designation in the European Union (EU) is granted by the European Commission based on a positive opinion adopted by the EMA Committee for Orphan Medicinal Products. Orphan designation provides incentives to developers of medicines for limited patient populations, including market exclusivity, protocol assistance (guidance on study design and scientific evaluation) and regulatory fee reductions. IgAN is a common, chronic autoimmune kidney disease that primarily affects young adults. In patients with the disease, a protein called immunoglobulin A (IgA) becomes trapped in the filters of the kidney, known as glomeruli, causing inflammation, damage and scarring to the whole kidney. There are currently no approved therapeutic options to stop disease progression, nor a cure, and about one third of high risk IgAN patients will go on to lose kidney function within five years and require a kidney transplant or dialysis. Haseeb Ahmad, Purespring's Chief Executive Officer, commented: 'Orphan drug designation will significantly support Purespring's goal of progressing PS-002 through clinical development and, more broadly, with bringing solutions for kidney disease indications to patients. We're delighted that the EMA has recognised the promise of this potential breakthrough medicine and we look forward to working with them on the development pathway. 'By developing a novel approach to treat IgAN, we believe we can offer hope to patients across Europe and globally who currently have limited therapeutic options, furthering our mission to transform the lives of people suffering from kidney diseases.' Supported by an oversubscribed £80 million / $105 million Series B financing, which completed in October 2024, Purespring is progressing PS-002 towards a Phase I/II clinical trial for IgAN, with additional gene therapy programmes in development for the treatment of both rare and common kidney diseases.
Yahoo
03-04-2025
- Health
- Yahoo
FDA grants accelerated approval to Novartis' Vanrafia for IgAN
The US Food and Drug Administration (FDA) has granted accelerated approval to Novartis' Vanrafia, a treatment aimed at decreasing proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk of rapid disease progression. The non-steroidal selective endothelin A (ETA) receptor antagonist is tailored for one-time-a-day oral administration and can be used alongside other supportive care options such as renin-angiotensin system (RAS) inhibitor, with or without a sodium-glucose co-transporter-2 (SGLT2) inhibitor. FDA's accelerated approval is supported by a prespecified interim analysis from the ongoing randomised Phase III ALIGN trial, which showed proteinuria minimisation at 36 weeks against a placebo. The trial assessed the safety and efficacy of the therapy against placebo in patients with IgAN. Subjects treated with the therapy in conjunction with a RAS inhibitor experienced a reduction of 36.1% in proteinuria, with improvements observed as early as week six and maintained through to week 36. Continued approval of the therapy is dependent on clinical benefit verification from the trial, assessing if the therapy slows the progression of disease according to a measure of estimated glomerular filtration rate (eGFR) decline data at week 136. This data is anticipated in 2026. Vanrafia ALIGN study investigator and Stanford University Medical Center Glomerular Disease Center director Professor Richard Lafayette stated: "Vanrafia is a selective ETA receptor antagonist that effectively reduces proteinuria, a major risk factor in IgAN. Taking early, decisive action is critical to help improve outcomes for these patients who too often progress toward kidney failure." A rare, progressive kidney disease, IgAN leads to glomerular inflammation and proteinuria, resulting from the immune system's attack on the kidneys. Vanrafia's accelerated approval is the third in the US for the company's kidney disease portfolio, following the agency's approvals for Fabhalta in C3 glomerulopathy in March 2025 and another accelerated approval for IgAN in August 2024. "FDA grants accelerated approval to Novartis' Vanrafia for IgAN" was originally created and published by Pharmaceutical Technology, a GlobalData owned brand. The information on this site has been included in good faith for general informational purposes only. It is not intended to amount to advice on which you should rely, and we give no representation, warranty or guarantee, whether express or implied as to its accuracy or completeness. You must obtain professional or specialist advice before taking, or refraining from, any action on the basis of the content on our site. Sign in to access your portfolio
