[Translation] A Phase I, open-label, randomized, parallel-group clinical study to evaluate the pharmacokinetic characteristics, safety, tolerability, and immunogenicity of BION-1301 after a single dose in healthy adult Chinese subjects

主要目的：评估中国健康成年受试者单次皮下注射（SC）BION-1301的药代动力学（PK）特征次要目的：评估中国健康成年受试者单次SC BION-1301后对免疫球蛋白的药效学（PD）影响；评估中国健康成年受试者单次SC BION-1301的免疫原性；评估中国健康成年受试者单次SC BION-1301的安全性和耐受性

[Translation]

Primary objective: To evaluate the pharmacokinetic (PK) characteristics of a single subcutaneous (SC) injection of BION-1301 in healthy Chinese adult subjects Secondary objectives: To evaluate the pharmacodynamic (PD) effects of a single SC BION-1301 on immunoglobulins in healthy Chinese adult subjects; To evaluate the immunogenicity of a single SC BION-1301 in healthy Chinese adult subjects; To evaluate the safety and tolerability of a single SC BION-1301 in healthy Chinese adult subjects

Start Date17 Apr 2023

Sponsor / Collaborator

Chinook Therapeutics, Inc.

[+3]

100 Clinical Results associated with Zigakibart

100 Translational Medicine associated with Zigakibart

100 Patents (Medical) associated with Zigakibart

Literatures (Medical) associated with Zigakibart

01 May 2024·Drugs

Drugs in Development to Treat IgA Nephropathy

Review

Author: Rimoldi, Chiara ; Locatelli, Francesco ; Allinovi, Marco ; Del Vecchio, Lucia ; Peiti, Silvia ; Comolli, Stefania

IgA nephropathy is a common glomerulonephritis consequent to the autoimmune response to aberrant glycosylated immunoglobulin (Ig) A antibodies. Although it has historically been considered a benign disease, it has since become clear that a substantial percentage of patients reach end-stage kidney failure over the years. Several therapeutic attempts have been proposed, with systemic steroids being the most prevalent, albeit burdened by possible serious adverse events. Thanks to the more in-depth knowledge of the pathogenesis of IgA nephropathy, new treatment targets have been identified and new drugs developed. In this narrative review, we summarise the molecules under clinical development for the treatment of IgA nephropathy. As a search strategy, we used PubMed, Google, ClinicalTrials.gov and abstracts from recent international congresses. TRF budesonide and sparsentan are the two molecules at a more advanced stage, just entering the market. Other promising agents are undergoing phase III clinical development. These include anti-APRIL and anti-BLyS/BAFF antibodies and some complement inhibitors. Other new possible strategies include spleen tyrosine kinase inhibitors, anti-CD40 ligands and anti-CD38 antibodies. In an era increasingly characterised by 'personalised medicine' and 'precision therapy' approaches and considering that the potential therapeutic armamentarium for IgA nephropathy will be very broad in the near future, the identification of biomarkers capable of helping the nephrologist to select the right drug for the right patient should be the focus of future studies.

04 Dec 2023·Clinical Kidney Journal

The contribution of a proliferation-inducing ligand (APRIL) and other TNF superfamily members in pathogenesis and progression of IgA nephropathy

Review

Author: Barratt, Jonathan ; Yeo, See Cheng

ABSTRACTAdvances in our understanding of the pathogenesis of immunoglobulin A nephropathy (IgAN) have led to the identification of novel therapeutic targets and potential disease-specific treatments. Specifically, a proliferation-inducing ligand (APRIL) has been implicated in the pathogenesis of IgAN, mediating B-cell dysregulation and overproduction of pathogenic galactose-deficient IgA1 (Gd-IgA1). Animal and clinical studies support the involvement of APRIL in the pathogenesis and progression of IgAN. An elevated level of APRIL is found in IgAN when compared with controls, which correlates with the level of Gd-IgA1 and associates with more severe disease presentation and worse outcomes. Conversely, anti-APRIL therapy reduces pathogenic Gd-IgA1 and IgA immune complex formation and ameliorates the severity of kidney inflammation and injury. Genome-wide association studies in IgAN have identified TNFSF13 and TNFRSF13B, a cytokine ligand-receptor gene pair encoding APRIL and its receptor, respectively, as risk susceptibility loci in IgAN, further supporting the causal role of the APRIL signalling pathway in IgAN. Several novel experimental agents targeting APRIL, including atacicept, telitacicept, zigakibart and sibeprenlimab, are currently under investigation as potential therapies in IgAN. Preliminary results suggest that these agents are well-tolerated, and reduce levels of Gd-IgA1, with corresponding improvement in proteinuria. Further studies are ongoing to confirm the safety and efficacy of anti-APRIL approaches as an effective therapeutic strategy in IgAN.

01 Dec 2023·Clinical Rheumatology

A narrative review of potential drug treatments for nephritis in children with IgA vasculitis (HSP)

Review

Author: Chetwynd, Andrew J ; Oni, Louise ; Marro, Julien ; Williams, Chloe E C ; Lamond, Megan

AbstractImmunoglobulin A (IgA) vasculitis (IgAV, also known as Henoch-Schoenlein purpura, HSP) is the most common vasculitis of childhood. It usually presents with a simple, self-limiting disease course; however, a small subset of patients may develop kidney involvement (IgAV-N) which occurs 4–12 weeks after disease onset and is the biggest contributor to long-term morbidity. Treatment currently targets patients with established kidney involvement; however; there is a desire to work towards early prevention of inflammation during the window of opportunity between disease presentation and onset of significant nephritis. There are no clinical trials evaluating drugs which may prevent or halt the progression of nephritis in children with IgAV apart from the early use of corticosteroids which have no benefit. This article summarises the latest scientific evidence and clinical trials that support potential therapeutic targets for IgAV-N that are currently being developed based on the evolving understanding of the pathophysiology of IgAV-N. These span the mucosal immunity, B-cell and T-cell modulation, RAAS inhibition, and regulation of complement pathways, amongst others. Novel drugs that may be considered for use in early nephritis include TRF-budesonide; B-cell inhibiting agents including belimumab, telitacicept, blisibimod, VIS649, and BION-1301; B-cell depleting agents such as rituximab, ofatumumab, and bortezomib; sparsentan; angiotensin converting enzyme inhibitors (ACE-Is); and complement pathway inhibitors including avacopan, iptacopan, and narsoplimab. Further clinical trials, as well as pre-clinical scientific studies, are needed to identify mechanistic pathways as there may be an opportunity to prevent nephritis in this condition.Key Points• Kidney involvement is the main cause of long-term morbidity and mortality in IgA vasculitis despite the current treatment recommendations.• The evolving understanding of the pathophysiology of IgA vasculitis is allowing exploration of novel treatment options which target underlying immune pathways.• Novel treatments currently being trialled in IgA nephropathy may have benefit in IgA vasculitis due to the similarities in the underlying pathophysiology, such as TRF-budesonide, B-cell modulators, and complement inhibitors.• Further studies, including clinical trials of novel drugs, are urgently needed to improve the long-term outcomes for children with IgA vasculitis nephritis.

102

News (Medical) associated with Zigakibart

26 Oct 2024

·www.prnewswire.com

Novartis oral Fabhalta® (iptacopan) sustained clinically meaningful results at one year in Phase III C3 glomerulopathy (C3G) trial

New APPEAR-C3G data show Fabhalta sustained proteinuria reduction at 12 months1 Upon Fabhalta initiation, improvement observed in estimated glomerular filtration rate (eGFR) slope – a key measure of kidney function – vs. patients' historic rapid decline1 Fabhalta also showed a favorable safety profile with no new safety signals1 Fabhalta is the only oral alternative complement pathway inhibitor to selectively target the underlying cause of C3G, an ultra-rare kidney disease with no approved treatments2-5 Novartis continues to advance multi-asset renal portfolio; C3G regulatory submissions completed in EU, China and Japan, and expected in US by year-end EAST HANOVER, N.J., Oct. 26, 2024 /PRNewswire/ -- Novartis today presented 12-month data from the Phase III APPEAR-C3G study at American Society of Nephrology (ASN) Kidney Week 2024 showing that patients with C3 glomerulopathy (C3G) treated with oral Fabhalta® (iptacopan) in addition to supportive care experienced clinically meaningful, sustained results at one year.1 These data confirm treatment with Fabhalta resulted in clinically meaningful proteinuria reduction, which was seen as early as 14 days, and sustained at 12 months. Similarly, in an open-label period of the study, proteinuria reduction was seen in participants who were switched to Fabhalta. In addition, improvement in estimated glomerular filtration rate (eGFR) slope was observed upon Fabhalta initiation compared to patients' historic rapid decline based on results from a prespecified exploratory analysis. Fabhalta showed a favorable safety profile, with no new safety signals.1 APPEAR-C3G evaluated the efficacy and safety of twice-daily oral Fabhalta in adult patients with C3G. The study was comprised of a 6-month randomized, double-blind treatment period with Fabhalta compared to placebo, followed by an additional 6-month open-label treatment period where all participants received Fabhalta.1 Results previously presented at the 2024 European Renal Association (ERA) Congress demonstrated a statistically significant and clinically meaningful 35.1% proteinuria reduction vs. placebo on top of supportive care at 6 months.6 Longer-term data show sustained results with oral Fabhalta "As a clinician treating young people living with C3G, I see firsthand the challenges with therapies used to treat this condition today, underscoring the vital need for dedicated treatment for these patients," said Carla Nester, M.D., M.S.A., F.A.S.N., Professor of Pediatrics-Nephrology at the University of Iowa and APPEAR-C3G Co-Investigator. "I am encouraged to see these data, which reinforce the clinically meaningful impact on kidney health measures we saw at 6 months. As the only oral complement inhibitor intended to treat C3G, Fabhalta could provide new hope for people living with this condition." "These results mark an important milestone for the management of C3G, as the first study to shed light on longer-term treatment targeting the underlying mechanism of this disease via the alternative complement pathway," said Andrew Bomback, M.D., M.P.H., Associate Professor of Medicine at Columbia University Irving Medical Center and APPEAR-C3G Co-Investigator and Steering Committee Member. "I am optimistic that these iptacopan APPEAR-C3G findings bring us a step closer to revolutionizing the treatment paradigm in this ultra-rare disease with no approved therapies." Approximately 50% of C3G patients progress to kidney failure within 10 years of diagnosis, at which point they require lifelong dialysis and/or kidney transplantation.4,7 Fabhalta, the only oral Factor B inhibitor of the alternative complement pathway, has potential to be the first US Food and Drug Administration (FDA) approved treatment for C3G.2,4,5 Regulatory submissions for Fabhalta in C3G are completed in the EU, China and Japan, and expected in US by year-end. Transforming patient care in kidney disease "We are thrilled to share these data, which demonstrate the potential of Fabhalta in C3G, and look forward to working with regulatory authorities with the goal of bringing this innovative medicine to this patient community," said David Soergel, M.D., Global Head, Cardiovascular, Renal and Metabolism Development Unit, Novartis. "Building on the longstanding experience of Novartis in nephrology and our first rare kidney disease approval in IgA nephropathy earlier this year, these results in C3G show continued advancement of our broad, industry-leading portfolio, which aims to transform care for these patients." Fabhalta, discovered at Novartis, received FDA approval in December 2023 for the treatment of adults with paroxysmal nocturnal hemoglobinuria (PNH) and accelerated approval in August 2024 for the reduction of proteinuria in certain adults with primary IgA nephropathy (IgAN).2 Fabhalta is being studied in a broad range of rare kidney diseases, including C3G, atypical hemolytic uremic syndrome (aHUS), immune complex membranoproliferative glomerulonephritis (IC-MPGN) and lupus nephritis (LN). Studies are ongoing to evaluate the safety and efficacy profiles in these investigational indications and support potential regulatory submissions. In addition to Fabhalta, Novartis is advancing the late-stage development of two additional IgAN therapies with highly differentiated mechanisms of action: atrasentan, an investigational oral endothelin A receptor antagonist that received FDA filing acceptance in Q2 2024, and zigakibart, an investigational subcutaneously administered anti-APRIL monoclonal antibody that is currently in Phase III development. A conference call to update investors on the Novartis renal portfolio will take place on Monday, October 28, 2024, at 8:00 am ET. Details can be found at Event calendar | Novartis. About APPEAR-C3G APPEAR-C3G (NCT04817618) is a Phase III multicenter, randomized, double-blind, parallel group, placebo-controlled study to evaluate the efficacy and safety of twice-daily oral Fabhalta (200 mg) in C3G patients. The study comprises a 6-month double-blind period in which adult patients were randomized 1:1 to receive Fabhalta or placebo on top of supportive care, followed by a 6-month open-label period in which all patients receive Fabhalta (including those who were previously on placebo). The primary endpoint for the double-blind period was proteinuria reduction from baseline at 6 months for Fabhalta compared to placebo as measured by 24-hour urine protein to creatinine ratio (UPCR).1,8 In addition to the results from adult patients with C3G, enrollment is ongoing in a separate cohort of adolescent patients with C3G.8 The majority of treatment-emergent adverse events (TEAEs) over the 12-month study period were mild to moderate in severity and there were no deaths, no cases of meningitis and/or meningococcal sepsis and no discontinuations due to TEAEs.1 About C3 glomerulopathy (C3G) C3G is an ultra-rare, progressive kidney disease that initially presents mostly in children and young adults.3,4,9 Each year, approximately 1-2 people per million worldwide are newly diagnosed with C3G, a form of membranoproliferative glomerulonephritis (MPGN).3 In C3G, overactivation of the alternative complement pathway – part of the immune system – causes deposits of C3 protein to build up in kidney glomeruli, which are a network of blood vessels that filter waste and remove extra fluids from the blood.9,10 This triggers inflammation and glomerular damage that results in proteinuria (protein in urine), hematuria (blood in urine) and reduced kidney function.9,11 Indication FABHALTA® (iptacopan) is a prescription medicine used to reduce protein in the urine (proteinuria) in adults with primary immunoglobulin A nephropathy (IgAN), who are at risk of their disease progressing quickly. It is not known if FABHALTA is safe and effective in children with IgAN. FABHALTA has been approved based on a reduction of proteinuria. Continued approval may require results from an ongoing study to determine whether FABHALTA slows decline in kidney function. Important Safety Information FABHALTA is a medicine that affects part of the immune system and may lower one's ability to fight infections. FABHALTA increases the chance of getting serious infections caused by encapsulated bacteria, including Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type b. These serious infections may quickly become life-threatening or fatal if not recognized and treated early. Patients must complete or update vaccinations against Streptococcus pneumoniae and Neisseria meningitidis at least 2 weeks before the first dose of FABHALTA. If patients have not completed vaccinations and FABHALTA therapy must be started right away, they should receive the required vaccinations as soon as possible. If patients have not been vaccinated and FABHALTA must be started right away, they should also receive antibiotics to take for as long as their doctor tells them. If patients have been vaccinated against these bacteria in the past, they might need additional vaccinations before starting FABHALTA. Their doctor will decide if they need additional vaccinations. Vaccines do not prevent all infections caused by encapsulated bacteria. Patients should call their doctor or get emergency medical care right away if they have any of these signs and symptoms of a serious infection: fever with or without shivers or chills, fever with chest pain and cough, fever with high heart rate, headache and fever, confusion, clammy skin, fever and a rash, fever with breathlessness or fast breathing, headache with nausea or vomiting, headache with stiff neck or stiff back, body aches with flu-like symptoms, or eyes sensitive to light. Doctors will give their patients a Patient Safety Card about the risk of serious infections. Patients must carry it with them at all times during treatment and for 2 weeks after their last dose of FABHALTA. The risk of serious infections may continue for a few weeks after their last dose of FABHALTA. It is important for patients to show this card to any doctor who treats them. This will help doctors diagnose and treat patients quickly. FABHALTA is only available through a program called the FABHALTA Risk Evaluation and Mitigation Strategy (REMS). Before patients can take FABHALTA, their doctor must enroll in the FABHALTA REMS program, counsel patients about the risk of serious infections caused by certain bacteria, give patients information about the symptoms of serious infections, make sure that patients are vaccinated against serious infections caused by encapsulated bacteria and that they receive antibiotics if they need to start FABHALTA right away and are not up to date on vaccinations, as well as give patients a Patient Safety Card about the risk of serious infections. Patients should not take FABHALTA if they are allergic to FABHALTA or any of the ingredients in FABHALTA. Patients should not take FABHALTA if they have a serious infection caused by encapsulated bacteria, including Streptococcus pneumoniae, Neisseria meningitidis, or Haemophilus influenzae type b when starting FABHALTA. Before taking FABHALTA, patients should tell their doctor about all their medical conditions, including if they have an infection or fever, have liver problems, are pregnant or plan to become pregnant (it is not known if FABHALTA will harm an unborn baby), or are breastfeeding or plan to breastfeed as it is not known if FABHALTA passes into breast milk. Patients should not breastfeed during treatment and for 5 days after the final dose of FABHALTA. Patients should tell their doctor about all the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Taking FABHALTA with certain other medicines may affect the way FABHALTA works and may cause side effects. Patients should know the medicines they take and the vaccines they receive. Patients should keep a list of them to show their doctor and pharmacist when they get a new medicine. FABHALTA may cause serious side effects, including those mentioned above as well as increased cholesterol and triglyceride (lipid) levels in the blood. Doctors will do blood tests to check patients' cholesterol and triglycerides during treatment with FABHALTA. Doctors may start patients on medicine to lower cholesterol if needed. The most common side effects of FABHALTA in adults include headache; nasal congestion, runny nose, cough, sneezing, and sore throat (nasopharyngitis); diarrhea; pain in the stomach (abdomen); infections (bacterial and viral); nausea; and rash. Please see full Prescribing Information, including Boxed WARNING and Medication Guide. Novartis in kidney disease At Novartis, our journey in nephrology began more than 40 years ago when the development and introduction of cyclosporine helped reimagine the field of transplantation and immunosuppression. We continue today with a broad renal R&D portfolio targeting the underlying causes of disease to preserve kidney function. We aim to help transform the lives of people living with kidney diseases, enabling them to live longer without the need for dialysis or transplantation. Disclaimer This press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as "potential," "can," "will," "plan," "may," "could," "would," "expect," "anticipate," "look forward," "believe," "committed," "investigational," "pipeline," "launch," "progress," "accelerated," "targets," "continued," "contingent," "progressive," "evolving," "enable," "innovation," "ongoing," "evaluating," "evolve," "committed," "advance," "advancing," "commitment," "to developing," "to provide, "development," "to address," or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for Fabhalta or the other investigational or approved products described in this press release, or regarding potential future revenues from such product. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that Fabhalta or the other investigational or approved products described in this press release will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that such products will be commercially successful in the future. In particular, our expectations regarding such products could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures and requirements for increased pricing transparency; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political, economic and business conditions, including the effects of and efforts to mitigate pandemic diseases; safety, quality, data integrity or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise. About Novartis Novartis is an innovative medicines company. Every day, we work to reimagine medicine to improve and extend people's lives so that patients, healthcare professionals and societies are empowered in the face of serious disease. Our medicines reach more than 250 million people worldwide. Reimagine medicine with us: Visit us at and and connect with us on LinkedIn, Facebook, X/Twitter and Instagram. References Smith RJ, Kavanagh D, Vivarelli M, et al. Efficacy and safety of iptacopan in patients with C3 glomerulopathy: 12-Month results from the Phase 3 APPEAR-C3G study. Presented at American Society of Nephrology (ASN) Kidney Week 2024; October 23-27, 2024; San Diego, CA. FABHALTA prescribing information. East Hanover, NJ: Novartis Pharmaceuticals Corp; August 2024. Schena FP, Esposito P, Rossini M. A Narrative Review on C3 Glomerulopathy: A Rare Renal Disease. Int J Mol Sci. 2020;21(2):525. Martín B, Smith RJH. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. C3 Glomerulopathy. GeneReviews® [Internet]. Updated 2018. University of Washington, Seattle; 1993-2024. Available from: . Accessed September 2024. Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney Int. 2021;100(4S):S1-S276. Kavanagh D, Bomback A, Vivarelli M, et al. Efficacy and Safety of Iptacopan in Patients with C3 Glomerulopathy: Results from the Phase 3 APPEAR-C3G Trial. Presented at European Renal Association (ERA) Congress; May 25, 2024; Stockholm, Sweden. Smith RJH, Appel GB, Blom AM, et al. C3 Glomerulopathy – understanding a rare complement-driven renal disease. Nat Rev Nephrol. 2019;15(3):129-143. ClinicalTrials.gov. Study of Efficacy and Safety of Iptacopan in Patients With C3 Glomerulopathy. (APPEAR-C3G). Available from: . Accessed September 2024. Caravaca-Fontán F, Lucientes L, Cavero T, Praga M. Update on C3 Glomerulopathy: A Complement-Mediated Disease. Nephron. 2020;144(6):272-280. Ravindran A, Fervenza FC, Smith RJH, Sethi S. C3 Glomerulopathy Associated with Monoclonal Ig is a Distinct Subtype. Kidney Int. 2018;94(1):178-186. Medjeral-Thomas NR, O'Shaughnessy MM, O'Regan JA, et al. C3 Glomerulopathy: Clinicopathologic Features and Predictors of Outcome. Clin J Am Soc Nephrol. 2014;9(1):46-53. ### SOURCE Novartis Pharmaceuticals Corporation WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Clinical ResultPhase 3Drug Approval

22 Oct 2024

·pipelinereview.com

Otsuka Announces Positive Interim Results from the Phase 3 Trial of Sibeprenlimab for the Treatment of Immunoglobulin A Nephropathy in Adults

PRINCETON, NJ, USA & TOKYO, Japan I October 22, 2024 I Otsuka Pharmaceutical Development & Commercialization, Inc. and Otsuka Pharmaceutical, Co. Ltd. (Otsuka), today announce positive topline interim data from the ongoing Phase 3 clinical trial of sibeprenlimab for the treatment of immunoglobulin A nephropathy (IgA nephropathy) in adults. Sibeprenlimab is an investigational, anti-APRIL monoclonal antibody ( A PR oliferation- I nducing L igand) that blocks a key initiating step in the immune pathogenic cascade of IgA nephropathy by limiting Gd-IgA1 production and immune complex formation. IgA nephropathy is a progressive, autoimmune, chronic kidney disease that can lead to end-stage kidney disease (ESKD) over the lifetime of most patients. 1,2,3,4 Otsuka was previously granted Breakthrough Therapy designation for sibeprenlimab following favorable results of the Phase 2 ENVISION clinical trial. 3 The pre-specified interim analysis review, conducted by an independent data monitoring committee, found that the Phase 3 VISIONARY study (NCT05248646) met its primary endpoint by demonstrating that sibeprenlimab produced a statistically significant and clinically meaningful reduction in 24-hour uPCR (urine protein-to-creatine ratio) compared to placebo after nine months of treatment. 5 The study, a multicenter, randomized, double-blind, placebo-controlled trial consisting of approximately 530 adult patients (largest of its kind) with IgA nephropathy who were receiving standard-of-care therapy (defined as maximally tolerated ACE inhibitor or ARB +/- SGLT2 inhibitor), was designed to evaluate the efficacy and safety of sibeprenlimab 400 mg administered subcutaneously every four weeks, compared to placebo. The primary efficacy endpoint was to evaluate the change in 24-hour uPCR at 9 months compared with baseline. 5 “The positive interim data from this trial suggest that by targeting APRIL, we could provide a new therapeutic strategy for people living with this progressive kidney disease,” said John Kraus, M.D., Ph.D., executive vice president and chief medical officer, Otsuka Pharmaceutical Development & Commercialization, Inc. “We look forward to the completion of this study and reviewing the full results at a future timepoint. We are deeply appreciative to the patients with IgA nephropathy who participated in this trial, their caregivers, and investigators, all of whom continue to contribute greatly to this research.” Brian Pereira, M.D., CEO of Visterra, Inc., an Otsuka U.S. affiliate, which designed and engineered sibeprenlimab, said, “We are encouraged by sibeprenlimab’s continuing progress and its potential to provide a needed and possibly disease-modifying treatment option to IgA nephropathy patients.” The ongoing Phase 3 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 IgA nephropathy. Otsuka plans to review interim analysis results with the FDA to enable a potential regulatory submission for accelerated approval. 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 blocks the action of APRIL ( A PR oliferation- I nducing L igand), that plays a key role in IgA nephropathy’s four-hit pathogenic cascade. APRIL is an important sustaining factor in IgA nephropathy progression by promoting the production of pathogenic Gd-IgA1 and immune complex formation. By binding and neutralizing APRIL, sibeprenlimab may help reduce the amount of immunoglobulin A (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 the kidney, and reduced proteinuria and kidney inflammation. By reducing the production of Gd-IgA1, sibeprenlimab may help slow kidney damage and progression toward ESKD. 1,2,3,5 By blocking APRIL, sibeprenlimab may help address one of the IgA nephropathy-specific drivers for nephron loss. About Immunoglobulin A Nephropathy and APRIL IgA nephropathy, also known as Berger’s disease, is a progressive, autoimmune, chronic kidney disease that typically manifests in adults aged 20-40 years and leads to ESKD over the lifetime of most patients. 4, 6, 7 It is characterized by the accumulation of IgA in the kidneys – a type of antibody that plays a critical role in the immune system.IgA nephropathy can lead to progressive kidney dysfunction and, eventually, ESKD, imposing a significant burden on patients. 6 Despite supportive care, including therapies that focus on treating the symptoms of IgA nephropathy, continued research in the disease remains crucial to uncovering opportunities for advancement in our understanding and treatment of patients. 6 APRIL ( A PR oliferation- I nducing L igand), a cytokine in the tumor necrosis factor (TNF) family, is integral to the development and progression of IgA nephropathy. 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. 8 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 34,400 people worldwide and had consolidated sales of approximately USD 14.2 billion in 2023. 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 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 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. Pitcher, D. Braddon, et. al Long-term outcomes in IGA nephropathy. Clinical journal of the American Society of Nephrology : CJASN. https://pubmed.ncbi.nlm.nih.gov/37055195/ . 5. Otsuka Pharmaceutical Development & Commercialization, Inc.Visionary Study: Phase 3 Trial of Sibeprenlimab in Immunoglobulin A Nephropathy (IgAN). Clinicaltrials.gov. 6. 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. 7. Lai K. Iga nephropathy. Nature reviews. Disease primers. 2016. https://pubmed.ncbi.nlm.nih.gov/27189177/ . 8. Yeo SC et al. Is immunoglobulin A nephropathy different in different ethnic populations? April 2019. https://onlinelibrary.wiley.com/doi/full/10.1111/nep.13592 . SOURCE: Otsuka Pharmaceuticals

Phase 2Clinical ResultPhase 3Breakthrough Therapy

22 Oct 2024

·endpts.com

Otsuka’s cytokine-targeting drug for IgAN clears Phase 3 hurdle

Otsuka Pharmaceutical’s 2018 purchase of Visterra seems to be paying off after its anti-APRIL antibody passed a registrational test in a rare kidney disease. The IgA nephropathy (IgAN) antibody, named sibeprenlimab, hit the trial’s primary endpoint by achieving a “statistically significant and clinically meaningful” reduction in 24-hour urine protein-to-creatine ratio versus placebo at nine months, according to a Tuesday release . The study enrolled 530 people with IgAN who were taking standard of care. Otsuka said it plans to review the interim data with the FDA with an eye to accelerated approval. Bank of America Securities analysts said sibeprenlimab could become a first-in-class biologic for IgAN with approval possible as soon as the second half of next year. The Phase 3 trial is ongoing and expected to end in 2026. The company is tracking the study’s secondary endpoints like change in kidney function over 24 months. The Japanese company added sibeprenlimab to its pipeline as part of its $430 million buyout of Visterra in 2018. The monoclonal antibody works by blocking APRIL, a cytokine that plays a key role in B cell dysregulation and the overproduction of galactose-deficient IgA1. The APRIL target has been at the heart of several major deals, including Vertex’s $4.9 billion acquisition of Alpine Immune Sciences and its dual BAFF/APRIL antagonist povetacicept, which is set to enter Phase 3 development this year. Last year, Novartis spent $3.2 billion on Chinook Therapeutics and its pipeline of kidney drugs, including anti-APRIL antibody zigakibart. Otsuka has projected its drug could reach more than 100 billion Japanese Yen ($663 million) in peak sales. The BofA analysts’ expectations were even higher at around 505 billion Japanese Yen ($3.3 billion) in 2035. Jefferies analysts said cross-trial comparisons suggest sibeprenlimab has best-in-class potential, as well as more convenient dosing. IgAN affects around 390,000 people in the US, EU and Japan, the analysts added. It is the leading cause of kidney disease in young people.

Phase 3AcquisitionClinical ResultDrug ApprovalAccelerated Approval

100 Deals associated with Zigakibart

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Glomerulonephritis, IGA	Phase 3	HR	Chinook Therapeutics, Inc.	27 Jul 2023
Glomerulonephritis, IGA	Phase 3	BR	Chinook Therapeutics, Inc.	27 Jul 2023
Glomerulonephritis, IGA	Phase 3	GB	Chinook Therapeutics, Inc.	27 Jul 2023
Glomerulonephritis, IGA	Phase 3	BE	Chinook Therapeutics, Inc.	27 Jul 2023
Glomerulonephritis, IGA	Phase 3	FR	Chinook Therapeutics, Inc.	27 Jul 2023
Glomerulonephritis, IGA	Phase 3	DE	Chinook Therapeutics, Inc.	27 Jul 2023
Glomerulonephritis, IGA	Phase 3	US	Chinook Therapeutics, Inc.	27 Jul 2023
Glomerulonephritis, IGA	Phase 3	AU	Chinook Therapeutics, Inc.	27 Jul 2023
Glomerulonephritis, IGA	Phase 3	JP	Chinook Therapeutics, Inc.	27 Jul 2023
Glomerulonephritis, IGA	Phase 3	CN	Chinook Therapeutics, Inc.	27 Jul 2023

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03945318 (ADU-CL-19, ISN WCN2023)	Phase 1/2	Glomerulonephritis, IGA APRIL \| IgA \| Gd-IgA1 ... View more	-	BION-1301 450 mg IV	bebnskayps(oqtszofgzt) = pbpijmqdyd zacxscupex (hfmiaiuvvi )	Positive	01 Mar 2023
				BION-1301 600 mg SC	bebnskayps(oqtszofgzt) = iddxhcboku zacxscupex (hfmiaiuvvi )
NCT03945318 (Phase 1/2 Study of BION-1301, ASN2022)	Phase 1/2	Glomerulonephritis, IGA APRIL \| IgA \| Gd-IgA1 ... View more	20	BION-1301 450 mg IV	ypwjvwkuse(pyqbhteksk) = ylwminsxsk uekufyazgi (rgujgakpox )	Positive	04 Nov 2022
				BION-1301 600 mg SC	ypwjvwkuse(pyqbhteksk) = dutwlviqmn uekufyazgi (rgujgakpox )
NCT03945318 (Corporate Publications) Manual	Phase 1/2	Glomerulonephritis, IGA	40	BION-1301 (450 mg Q2W IV → 600 mg Q2W SC, up to 104 weeks ‖)	(mmvovajkjr) = ewfknlbhrb itqcbvvnco (aesriivfdo ) View more	Positive	01 Nov 2022
				BION-1301 (600 mg Q2W de novo SC, up to 104 weeks)	(bvnhaeyigq) = ouunkyxdzo gaazpasozd (asjqlphnfi )
NCT03945318 (Corporate Publications) Manual	Phase 1/2	Glomerulonephritis, IGA	10	BION-1301	(mzbuqlnvnf) = ylcmvltzwq nabqdglivs (yhdsmlleco ) View more	Positive	04 Nov 2021
NCT03340883 (CTgov)	Phase 1/2	Relapse multiple myeloma \| Plasma cell myeloma refractory	21	BION-1301 (BION-1301 50 mg Q2W)	(ymqhujtqum) = cvyvmzjckc ffltpxrdku (yuuoxoxxaf, kqqdouovbi - dpkitfbppy) View more	-	07 Sep 2020
				BION-1301 (BION-1301 150 mg Q2W)	(ymqhujtqum) = boxhbptrzq ffltpxrdku (yuuoxoxxaf, kdberpizop - lkwofremot) View more
NCT03340883 (ASCO2019) Manual	Phase 1	Plasma cell myeloma refractory	15	Zigakibart	(davhoctcfc) = none mmjxqmyjol (tfygupvsog ) View more	Negative	03 Jun 2019
BION-1301 (ASN2018)	Not Applicable	Glomerulonephritis, IGA APRIL \| BCMA \| TACI	-	BION-1301	xorjqmycgv(ptwxmmqwhk) = hgjikaijff pfukyjinqt (ufjutypsmn, 0.89) View more	Positive	23 Oct 2018

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

Zigakibart

Overview

Basic Info

Gene Sequence

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation