Latest news with #proteinuria
Reuters
08-06-2025
- Business
- Reuters
Otsuka's kidney disease therapy trial results heat up battle with rival Vera
June 6 (Reuters) - Otsuka's (4578.T), opens new tab experimental therapy for a potentially life-threatening kidney disease more than halved severe levels of protein in the urine of patients, intensifying the battle for an effective new treatment with rival Vera Therapeutics (VERA.O), opens new tab. The Japan-based company said on Friday its therapy, sibeprenlimab, cut proteinuria levels by 51.2% in patients with Immunoglobulin A Nephropathy, also known as Berger's disease, at nine months in a late-stage trial. The data comes just days after Vera said its drug, atacicept, reduced protein levels in patients' urine by 46%, compared with a 7% reduction with a placebo, meeting the main goal of a 428-patient late-stage study. Shares of the U.S.-based drug developer slid 31% to $20.89. Analysts, however, said that though data from Otsuka's sibeprenlimab might look superior, it was unlikely that doctors would interpret it that way. The difference between the two datasets is not too clinically diverse to affect demand for Vera's drug, said Jefferies analyst Farzin Haque. Berger's disease causes abnormal protein buildup in the kidneys and could eventually lead to the organ's failure. Analysts have estimated the U.S. market for its treatments could be worth as much as $10 billion. Otsuka has already applied for the FDA's accelerated approval for its therapy to treat the disease. However, its sales would largely depend on whether the treatment can improve kidney function, analysts said. Even if the drug gains accelerated approval, Otsuka said it plans to study whether it can preserve the organ's ability to filter toxins from blood, measured as the glomerular filtration rate (eGFR). "The magnitude of the protein reduction should translate into eGFR preservation down the line, because ultimately that's what patients are going to be asking for," Dana Rizk, the trial's investigator and a professor of medicine at the University of Alabama in Birmingham, told Reuters. The study is expected to be completed in early 2026.
Associated Press
06-06-2025
- Business
- Associated Press
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)--Jun 6, 2025-- 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 View source version on CONTACT: Contacts for MediaOtsuka in the Murphy Corporate Communications Otsuka America Pharmaceutical, Inc. [email protected]+1 609 249 7262Otsuka in JapanJeffrey Gilbert Leader, Pharmaceutical PR Otsuka Pharmaceutical Co., Ltd. [email protected]+81 3 6361 7379 KEYWORD: UNITED STATES JAPAN NORTH AMERICA ASIA PACIFIC NEW JERSEY INDUSTRY KEYWORD: SCIENCE BIOTECHNOLOGY RESEARCH PHARMACEUTICAL HEALTH FDA CLINICAL TRIALS OTHER HEALTH SOURCE: Otsuka Pharmaceutical Co., Ltd. Copyright Business Wire 2025. PUB: 06/06/2025 06:00 AM/DISC: 06/06/2025 05:58 AM
National Post
22-05-2025
- Health
- National Post
New AURORA 1 Analysis: LUPKYNIS-Based Triple Immunosuppressive Therapy Yields Deep Proteinuria Reduction in Lupus Nephritis
Article content ROCKVILLE, Md. & EDMONTON, Alberta — Aurinia Pharmaceuticals Inc. (NASDAQ: AUPH) (Aurinia or the Company), today announced that a post-hoc analysis of the 52-week, Phase 3 AURORA 1 study showed that lupus nephritis (LN) patients who received triple immunosuppressive therapy with LUPKYNIS ® (voclosporin), mycophenolate mofetil (MMF), and low-dose glucocorticoids achieved lower proteinuria targets at substantially higher rates compared to patients in the control group who received mycophenolate mofetil (MMF) and low-dose glucocorticoids alone. Article content The analysis assessed the achievement of urine protein creatine ratio (UPCR) targets of ≤0.4 g/g, ≤0.3 g/g, ≤0.2 g/g (classified as ultra-low UPCR), and ≤0.1 g/g in LN patients treated with LUPKYNIS-based triple immunosuppressive therapy compared to patients in the control group. Of the 357 patients in AURORA 1, 60.9% in the triple immunosuppressive therapy group (N=109) achieved a UPCR of ≤0.4 g/g at least once during the study compared to 37.1% of patients in the control group (N=66). Patients in the triple immunosuppressive therapy group also achieved higher rates of all other UPCR targets compared to patients in the control group. Adverse event rates were comparable in both groups. Article content 'It is widely known that no level of proteinuria is safe for nephrons and that early reductions in proteinuria are predictive of better long-term kidney outcomes. Yet, UPCR endpoints have varied widely across clinical trials and in clinical practice,' said lead study author Maria Dall'Era, M.D., Professor of Medicine in the Division of Rheumatology, University of California, San Francisco. 'This analysis shows that achieving UPCR targets of ≤0.4 g/g may be a feasible goal and that a voclosporin-based triple immunosuppressive therapy regimen can reduce proteinuria to profoundly low levels in a proportion of patients.' Article content An additional post-hoc analysis from the AURORA 1 study evaluated lipidomic profiles in LN patients based on achievement of proteinuria reductions, including ultra-low UPCR, at Week 52. The analysis found a distinct lipidomic profile in patients who achieved ultra-low UPCR. This analysis builds upon a previous analysis of AURORA 1 in which patients who received triple immunosuppressive therapy with LUPKYNIS achieved significantly greater improvements in total and low-density lipoprotein (LDL) cholesterol compared to those in the control group. While further research is needed to clarify the role of certain lipids in the biochemistry of LN patients, these preliminary findings suggest that attaining ultra-low UPCR targets may provide additional benefits to LN patients and contribute to modification of cardiovascular disease risk. Article content An analysis of real-world baseline data from ENLIGHT-LN, a U.S.-based prospective, observational registry of adult LN patients treated with LUPKYNIS, was also presented at LUPUS 2025. 'The data presented at LUPUS 2025 highlight the critical role of LUPKYNIS in improving health outcomes for LN patients. Early reduction of proteinuria to the lowest possible levels and long-term preservation of kidney health are key goals of LN therapy. These data provide compelling evidence that LUPKYNIS-based therapy can achieve significantly lower UPCR targets, potentially reducing the risk of significant kidney damage and other comorbidities,' said Dr. Greg Keenan, Chief Medical Officer of Aurinia. Article content Title: Attainment of Ultra-Low Levels of UPCR in the AURORA 1 Study Associated with Alterations in the Circulating Lipidome Authors: Farsad Afshinnia, Subramaniam Pennathur, Michelle Zubrycki, Linda Rehaume, Lucy Hodge Date: Thursday, May 22 Time: 12:10 – 1:10 PM ET Abstract Number: 252 Article content About LUPKYNIS Article content LUPKYNIS is a second generation calcineurin inhibitor with a dual mechanism of action, acting as an immunosuppressant through inhibition of T-cell activation and cytokine production and promoting podocyte stability in the kidney. The AURORA Clinical Program, comprised of the AURORA 1 pivotal trial and AURORA 2 extension trial, demonstrated the importance of triple immunosuppressive therapy with LUPKYNIS, mycophenolate mofetil, and low-dose glucocorticoids to preserve kidney health in lupus nephritis patients without reliance on chronic high-dose glucocorticoids. It is the only clinical program in lupus nephritis to include three years of triple immunosuppressive therapy. Article content About Aurinia Article content Aurinia Pharmaceuticals is a fully integrated biopharmaceutical company focused on delivering therapies to people living with autoimmune diseases with high unmet medical needs. In January 2021, the Company introduced LUPKYNIS ® (voclosporin), the first FDA-approved oral therapy dedicated to the treatment of adult patients with active lupus nephritis. Aurinia is also developing AUR200, a differentiated, potential best-in-class therapy for autoimmune diseases that targets both BAFF (B-cell Activating Factor) and APRIL (A Proliferation-Inducing Ligand). Article content LUPKYNIS is indicated in combination with a background immunosuppressive therapy regimen for the treatment of adult patients with active lupus nephritis (LN). Article content Limitations of Use: Safety and efficacy of LUPKYNIS have not been established in combination with cyclophosphamide. Use of LUPKYNIS is not recommended in this situation. Article content CONTRAINDICATIONS: LUPKYNIS is contraindicated in patients taking strong CYP3A4 inhibitors because of the increased risk of acute and/or chronic nephrotoxicity, and in patients who have had a serious/severe hypersensitivity reaction to LUPKYNIS or its excipients. Article content WARNINGS AND PRECAUTIONS Article content Lymphoma and Other Malignancies: Immunosuppressants, including LUPKYNIS, increase the risk of developing lymphomas and other malignancies, particularly of the skin. The risk appears to be related to increasing doses and duration of immunosuppression rather than to the use of any specific agent. Article content Serious Infections: Immunosuppressants, including LUPKYNIS, increase the risk of developing bacterial, viral, fungal, and protozoal infections, including opportunistic infections. These infections may lead to serious, including fatal, outcomes. Article content Nephrotoxicity: LUPKYNIS, like other calcineurin inhibitors (CNIs), may cause acute and/or chronic nephrotoxicity. The risk is increased when CNIs are concomitantly administered with drugs associated with nephrotoxicity. Monitor eGFR regularly. Article content Hypertension: Hypertension is a common adverse reaction of LUPKYNIS therapy and may require antihypertensive therapy. Monitor blood pressure regularly. Article content Neurotoxicity: LUPKYNIS, like other CNIs, may cause a spectrum of neurotoxicities: severe include posterior reversible encephalopathy syndrome (PRES), delirium, seizure, and coma; others include tremor, paresthesia, headache, and changes in mental status and/or motor and sensory functions. Monitor for neurologic symptoms. Article content Hyperkalemia: Hyperkalemia, which may be serious and require treatment, has been reported with CNIs, including LUPKYNIS. Concomitant use of agents associated with hyperkalemia may increase the risk for hyperkalemia. Monitor serum potassium levels periodically. Article content QTc Prolongation: LUPKYNIS prolongs the QTc interval in a dose-dependent manner when dosed higher than the recommended lupus nephritis therapeutic dose. The use of LUPKYNIS in combination with other drugs that are known to prolong QTc may result in clinically significant QT prolongation. Article content Immunizations: Avoid the use of live attenuated vaccines during treatment with LUPKYNIS. Inactivated vaccines noted to be safe for administration may not be sufficiently immunogenic during treatment with LUPKYNIS. Article content Pure Red Cell Aplasia: Cases of pure red cell aplasia (PRCA) have been reported in patients treated with another CNI immunosuppressant. If PRCA is diagnosed, consider discontinuation of LUPKYNIS. Article content Drug-Drug Interactions: Avoid co-administration of LUPKYNIS and strong CYP3A4 inhibitors or with strong or moderate CYP3A4 inducers. Co-administration of LUPKYNIS with strong CYP3A4 inhibitors is contraindicated. Reduce LUPKYNIS dosage when co-administered with moderate CYP3A4 inhibitors. Avoid use of LUPKYNIS with strong or moderate CYP3A4 inducers. Article content ADVERSE REACTIONS Article content The most common adverse reactions (≥3%) were glomerular filtration rate decreased, hypertension, diarrhea, headache, anemia, cough, urinary tract infection, abdominal pain upper, dyspepsia, alopecia, renal impairment, abdominal pain, mouth ulceration, fatigue, tremor, acute kidney injury, and decreased appetite. Article content SPECIFIC POPULATIONS Article content Pregnancy: Avoid use of LUPKYNIS. Article content Lactation: Consider the mother's clinical need for LUPKYNIS and any potential adverse effects to the breastfed infant when prescribing LUPKYNIS to a lactating woman. Article content Renal Impairment: LUPKYNIS is not recommended in patients with baseline eGFR ≤45 mL/min/1.73 m 2 unless benefit exceeds risk. If used in this population, reduce LUPKYNIS dose. Article content Dall'Era M. et al. Achievement of Proteinuria Less Than 0.4 G/G in the Phase 3 AURORA 1 Study of Voclosporin in Lupus Nephritis. Presented at LUPUS 2025 Congress, 2025, Toronto, CA. Geraldino-Pardilla L. et al. Baseline Demographics, Clinical Characteristics, and Treatment Regimens of an Initial Cohort of Patients Receiving Voclosporin for Lupus Nephritis in the Enlight-LN Registry. Presented at LUPUS 2025 Congress, 2025, Toronto, CA. Afshinnia F. et al. Attainment of Ultra-Low Levels of UPCR in the AURORA 1 Study Associated with Alterations in the Circulating Lipidome. Presented at LUPUS 2025 Congress, 2025, Toronto, CA. Arriens C. et al. Arthritis Care & Research. Vol. 75, No. 7, July 2023, pp 1399–1408. Article content Article content Article content Article content Article content Contacts Article content Article content
