Latest news with #sibeprenlimab
Reuters
3 days ago
- 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.
Medscape
5 days ago
- Health
- Medscape
Sibeprenlimab Halves uPCR in IgA Nephropathy Trial
VIENNA — Sibeprenlimab, a novel selective immune antibody, reduced the urine protein-to-creatinine ratio (uPCR) by more than half in patients with immunoglobulin A (IgA) nephropathy, according to an interim analysis of the VISIONARY trial. Beyond this clinical effect, a notable observation was the lack of safety concerns, especially given that, although sibeprenlimab is a selective agent, there may have been unexpected off-target effects. 'Safety's been a key consideration with these drugs,' study presenter Vlado Perkovic, MD, PhD, provost and scientia professor, University of New South Wales, Sydney, Australia, told Medscape Medical News . Sibeprenlimab represents a new mechanism of action and 'we don't yet fully understand the profile, so we've been looking at that data very carefully,' explained Perkovic. 'In particular, the infection risk has been my biggest concern, given we know that infections are dramatically increased in people with steroid therapy for example, in IgA nephropathy.' The results of the trial — the largest to date in the field — were presented at the 62nd European Renal Association Congress 2025 on June 6 and drew a warm applause from the audience. An Underestimated Condition IgA nephropathy is estimated to affect 2.5 per 100,000 people per year, although 'it's possible that that number is a significant underestimate,' said Perkovic. Diagnosis typically occurs between 20 and 40 years of age. And, despite supportive care, the majority of patients have a high lifetime risk of end-stage kidney disease (ESKD), with up to 50% of patients progressing to ESKD within 20 years of their clinical presentation. 'It's quite likely we've underestimated just how important this condition is,' said Perkovic, but 'we're fortunate that we're in the middle of something of a golden age of developing new treatments.' A number of therapies have been shown to reduce the risks associated with the disease, although they do not necessarily address the immunological basis of the condition. In addition to newer treatments, 'corticosteroids have long been used for people with IgA nephropathy,' Perkovic said, 'but of course, corticosteroids also have a range of different effects across the immune system,' which can lead to adverse outcomes. Sibeprenlimab is a selective IgG2 antibody that binds to and inhibits the biological activity of APRIL (a proliferation-inducing ligand), which is produced by mucosal epithelial and myeloid cells and binds to B cells. APRIL regulates B-cell-mediated immune responses and mediates IgG and IgA class switching in mature B cells. It is these two actions that make APRIL a key factor in the so-called 4-Hit process in the pathogenesis of IgA nephropathy, which results in the deposition of immune complexes in the glomerulus, leading to proteinuria and loss of kidney function. Phase 3 VISIONARY TRIAL Following on from the successful phase 2 ENVISION trial of sibeprenlimab, the researchers undertook the phase 3 VISIONARY trial, an ongoing study involving patients with biopsy-confirmed IgA nephropathy from 240 sites in 31 countries, who were randomized to sibeprenlimab or placebo for 100 weeks and followed up for a further 12 weeks. All patients were required to have a uPCR of ≥ 0.75 g/g or urine protein excretion of ≥ 1.0 g/day, an estimated glomerular filtration rate (eGFR) of ≥ 30 mL/min/1.73 m2, and to have been on a stable dose of either an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, with or without a SGLT2 inhibitor, for ≥ 3 months prior to screening. For the current pre-specified interim analysis, Perkovic reported the efficacy and safety results in the first 320 randomized patients (152 in the sibeprenlimab group and 168 in the placebo group), focusing on the primary endpoint of 24-hour uPCR at 9 months vs baseline, with eGFR and other data expected to be presented in 2026. The median age of the patients was 42-43 years. There were proportionally fewer females in the sibeprenlimab group (34.2%) vs the placebo group (40.5%). The majority of the patients were Asian, at 61.8% and 56.5%, respectively. Compared with a rise in uPCR at the 9-month follow-up in the placebo group, sibeprenlimab was associated with a 50.2% reduction in uPCR, giving a highly significant placebo-adjusted treatment effect of 51.2% ( P < .0001). Importantly, the benefit of sibeprenlimab on uPCR was seen as early as 4 weeks after initiating treatment and continued to accrue throughout follow-up. Ronald T. Gansevoort, MD, PhD, professor of medicine and a nephrologist at the Department of Nephrology, University Medical Center Groningen, Netherlands, who co-chaired the session, told Medscape Medical News that the results look 'very promising.' 'Recently, we have had several agents working in different ways that all show proteinuria lowering,' he continued, but the results from those studies show that the improvements seen in VISIONARY are 'the best proteinuria lowering' seen so far. Gansevoort noted, however, that this remains an interim analysis, and that he is really looking forward to seeing the kidney function results, adding: 'It was a little bit of a pity that they were not allowed to show at least the 9-month interim data on kidney function, which would have been so interesting.' Safety Results In terms of safety, the proportion of patients experiencing a treatment-related treatment-emergent adverse event (TEAE) was marginally lower with sibeprenlimab, at 32.9% vs 31.0% with placebo. The proportion of patients having a TEAE that led to treatment discontinuation was 0.7% vs 2.4%, respectively, and there were fewer severe and serious TEAEs with the experimental drug. 'If we focus on the infection-related adverse events,' Perkovic said, 'we can see that rates were numerically slightly higher in the sibeprenlimab than the placebo group, with a pattern that was broadly consistent, but with perhaps a slight excess of COVID 19.' He noted that this was 'the reverse of the pattern we've seen in the phase 2 trials, suggesting a chance' outcome. 'The data so far look remarkably encouraging,' he added. There's really no suggestion of an increased risk of infection,' with no opportunistic infections identified, 'and certainly no deaths.' More data is required from the ongoing follow-up to support what has been observed so far, but if the final results do bear out both the efficacy and safety outcome, it will show that sibeprenlimab is 'a precision approach to the fundamental abnormality in IgA nephropathy: that's the really exciting part,' said Perkovic. The study was funded by Otsuka Pharmaceutical Development and Commercialization. Perkovic declares relationships with Amgen, AstraZeneca, Bayer, Biogen, Boehringer Ingelheim, Chinook Therapeutics, Eli Lilly & Company, Gilead Sciences, GlaxoSmithKline, Guard Therapeutics, Incyte, Janssen, Merck, Mitsubishi Tanabe Pharma, Mundipharma, Novartis, Novo Nordisk, Otsuka, Pfizer, Roche, Sanofi, Shaanxi Micot Technology, Travere Therapeutics.
Associated Press
6 days ago
- 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
