Obinutuzumab lupus We collated data from nine SLE patients Positive topline results were announced from a phase 3 study of obinutuzumab in patients with lupus nephritis. 4,36. The addition of Background/Purpose: Patients with LN who received obinutuzumab, a humanized type II anti-CD20 monoclonal antibody, with standard-of-care (MMF) immunosuppression (Phase II NOBILITY; NCT02550652; PMID 34615636) showed improved clinical responses through Week 104 versus those who received MMF alone. “I B-cell depletion with obinutuzumab for the treatment of proliferative lupus nephritis: a randomised, double-blind, placebo-controlled trial Richard A Furie 1, Gustavo Aroca 2 , Matthew D Cascino 3 , Jay P Garg 3 , Brad H Rovin 4 , Analia Alvarez 5 , Hilda Fragoso-Loyo 6 , Elizabeth Zuta-Santillan 7 , Thomas Schindler 8 , Paul Brunetta 3 , Despite the improved treatment strategy for lupus nephritis, 22% of patients still develop renal failure . 1 Despite numerous advances in the treatment of active lupus nephritis, including the regulatory approvals of belimumab in 2020 and voclosporin in 2021, 2, 3 of belimumab in lupus nephritis. Immunosuppressants in lupus nephritis. The type II anti-CD20 antibody obinutuzumab (GA101) is more effective than rituximab at depleting B cells and treating disease in a murine lupus model. Management of lupus nephritis has evolved considerably over the past years. Both therapies target B cells, immune-system cells involved in the production of autoantibodies and lupus disease activity, but Gazyva exhibits more direct B-cell Obinutuzumab (Gazyva) in Active Lupus Nephritis: Post Hoc Analysis of a Phase 2 Trial – Abstract #0659. In the study, a higher proportion of people treated with Gazyva/Gazyvaro plus standard therapy (mycophenolate mofetil and glucocorticoids) achieved a complete renal response (CRR) at 76 weeks Obinutuzumab has recently been proven as an effective option in proliferative lupus nephritis leading to significantly better renal response compared with placebo. N Engl J Med 2020; 383: 1117–28. Ann Rheum Dis. Obinutuzumab. Top-line data could be available in the fall or winter of next year, and the study is due to finish in 2029. In development as a potential Positive topline results were announced from a phase 3 study of obinutuzumab in patients with lupus nephritis. Of note, obinutuzumab was not associated with increases in serious adverse events, serious infections or deaths, but non-serious infusion-related reactions occurred more frequently with the The new drug application for the investigational therapy, ATA3219, for treatment of systemic lupus erythematosus (SLE) with kidney involvement (lupus nephritis) was approved for study by the U. Objectives We set out to evaluate the clinical efficacy and Gazyva®/Gazyvaro® (obinutuzumab) is a Type II engineered humanised monoclonal antibody designed to attach to CD20, a protein found on certain types of B cells. Furie, 1 Jorge A. Lupus nephritis remains a severe and therapeutically challenging manifestation of systemic lupus erythematosus. 3 Furie R, Aroca G, Alvarez A, et al. Obinutuzumab is a next-generation humanized type-2 anti-CD20 therapy licensed for hematological malignancies which may overcome this issue(2). We hypothesized that a Type II anti-CD20 mAb with a different mechanism–obinutuzumab (GA101)—could be Positive Phase-III-Ergebnisse zu Obinutuzumab zeigen Überlegenheit gegenüber alleiniger Standardtherapie bei Patienten mit Lupus-Nephritis. We suggest that obinutuzumab should be given when B-cell repopulation occurs. 6 months), abatacept-30mg (20. Belimumab and obinutuzumab, as After obinutuzumab, 4/9 patients received 5mg and were in Lupus Low Disease Activity State (LLDAS). ekir Successful management of belimumab after obinutuzumab in a patient with systemic lupus erythematosus: a case report with an 18-month follow-up Front Immunol . 2024 Oct 3:15:1459241. Roche announced positive topline results from the phase III REGENCY study of Gazyva/Gazyvaro (obinutuzumab) in people with active lupus nephritis. However, its mechanism of action also suggests Gazyva may be useful to prevent excessive inflammation associated with several autoimmune diseases, including lupus. Conclusions: Obinutuzumab has shown promising results in a case series of patients with phospholipase A 2 receptor-associated membranous nephropathy and mixed results in systemic lupus erythematosus. The BTD classification is designed to accelerate the development and review of medicines intended to Depleting pathogenic B cells could treat SLE. The purpose of this clinical trial is to compare the effects, good or bad, of obinutuzumab against placebo in patients with lupus nephritis. The major search headings focused on ‘lupus nephritis,’ ‘B cell-targeting biological agents,’ ‘belimumab,’ ‘rituximab,’ ‘ocrelizumab,’ ‘obinutuzumab,’ ‘anifrolumab. About. This is the first time a person in the US has received an allogeneic NK cell (natural killer cell, a type of white blood cell that plays a critical role in the immune system, particularly in the detection and Serious infections were recorded in 8% in the obinutuzumab group and in 18% in the placebo group, making obinutuzumab not only an efficacious but also a safe choice in the management of lupus Das Potenzial von Obinutuzumab bei Lupus nephritis wird in der Phase-3-Studie REGENCY weiter untersucht, stellte der Experte in Aussicht. Two-year results from NOBILITY are reported Feb 16, 2024 · Background Secondary inefficacy characterized by infusion reactions and anti-drug antibodies occur in 14% of SLE patients treated with repeat rituximab courses(1). 8 months), and belimumab (23. Ruiz-Irastorza, in Revista Clínica Española (English Edition), 2023 Obinutuzumab. Obinutuzumab Benefits Patients With Active Lupus Nephritis Irrespective of Baseline Proteinuria Severity: a Post Hoc Analysis of the Phase II Nobility Trial Richard A. Lupus nephritis (LN) is a serious kidney complication associated with systemic lupus erythematosus (SLE), marked by the immune system's misdirected attack on kidney tissues, resulting in inflammation and compromised filtration. The purpose of this study is to compare the effects, good or bad, of obinutuzumab compared to a medication that looks like a drug but has no active ingredient (placebo) on participants with lupus nephritis. This review will discuss approved and target-specific therapeutics in development that bring hope for better Treatment of systemic lupus erythematosus: new therapeutic options. research study. The analysis assessed achievement of Based on the results from this study, the use of obinutuzumab in proliferative lupus nephritis is being further evaluated in a global phase 3 study (NCT04221477). 2022;81(1):100–107. Additionally, potential concerns regarding its safety were defeated due to a lower rate of adverse events in the obinutuzumab group when compared with the placebo group. Although promising data are emerging for B-cell-modulating biologics such as belimumab and obinutuzumab, 2,3. showing varied efficacy. Based on the results from this study, the use of obinutuzumab in proliferative lupus nephritis is being further evaluated in a The therapy is a monoclonal antibody that binds CD20, a protein found on the surface of certain healthy and malignant B-cells, destroying them. In 2017, 2 years after the last (effective) rituximab infusion, a renal relapse occurred (proteinuria up to 11 g/24 h with class III nephritis at repeat Background/Purpose: NOBILITY demonstrated improved renal responses and complete B-cell depletion with the humanized type II anti-CD20 monoclonal antibody obinutuzumab (OBI) compared with placebo (PBO) through 18 months in patients with proliferative lupus nephritis (LN) when added to standard of care therapies [1]. Despite available therapies [1], persistently active and corticosteroid-dependent SLE remains a major therapeutic challenge [2] and Treat-to-Target (T2T) strategies with the ultimate goal of While many drug candidates which met the end points in phase II trials have failed phase III trials, the number of target-specific therapies for SLE has continued to expand. , Gazyva is part of a collaboration between Genentech, a subsidiary of Roche, and Biogen. Expert opinion criteria for systemic lupus erythematosus and had biopsy-proven proliferative LN • Lupus nephritis (LN) is the most common severe organ-threatening manifestation of systemic lupus erythematosus1 – Obinutuzumab, a humanized type II anti-CD20 monoclonal antibody, enhances B-cell depletion These findings are consistent with previous studies investigating the efficacy of Obinutuzumab for various indications, including lupus nephropathy 16, 35, 36 and MN. Editing and writing assistance for this article was provided Feb 26, 2024 · The Food & Drug Administration (FDA) has granted Fast Track designation to the investigational therapy, AlloNK® (also known as AB-101), to be used in combination with rituximab or obinutuzumab, as a possible treatment for lupus nephritis, (LN, lupus-related kidney disease). S. It is a monoclonal antibody that works by blocking At least 50% of all patients with systemic lupus erythematosus (SLE) will manifest kidney involvement, or lupus nephritis (LN), in the course of the disease. Objectives We set out to evaluate the clinical efficacy and safety Obinutuzumab-Based Regimen in Lupus Nephritis To the Editor: A 47-year-old man diagnosed with class V lupus nephritis in 1993 has been treated over the years with cyclophosphamide, azathioprine, mycophenolate, and rituximab. Sunday 12 January 2025. Le lupus systémique est une maladie auto-immune systémique d’expression clinique très hétérogène. Obinutuzumab is a humanized anti-CD20 monoclonal antibody (unlike rituximab, which is chimeric) of type II that induces potent and rapid B-cell depletion. After promising 18-month outcomes in patients with proliferative lupus nephritis, obinutuzumab showed sustained benefits through 2 years of treatment for patients burdened with the rheumatic disease. B-cell-directed therapy has attracted much attention because of its unique mechanism of action. Successful phase II trials have recently been reported for obinutuzumab and telitacicept with larger confirmatory trials currently underway. . , 2022) It is given as two 1000mg intravenous infusions at 2 weeks apart, and its use in SLE is off label. Askanase, MD, MPH, shares potential highlights for the upcoming ACR Convergence 2024 and how excitement is building in the area of lupus therapeutics development, including two phase 3 We would like to show you a description here but the site won’t allow us. Editing and writing assistance for this article was provided Sep 30, 2024 · Swiss pharma giant Roche has announced positive top-line results from the Phase III REGENCY study of Gazyva/Gazyvaro (obinutuzumab) in people with active lupus nephritis. Obinutuzumab was well tolerated and no new safety The NOBILITY (A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Evaluate the Safety and Efficacy of Obinutuzumab in Patients With ISN/RPS 2003 Class III or IV Lupus Nephritis) trial randomized 126 patients Gazyva is a monoclonal antibody that has been designed to bind CD20, a protein found on the surface of certain types of B cells, including malignant chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) cells, destroying them. Seven patients (70%) had received rituximab within a year before receiving obinutuzumab Además de estos, existen múltiples fármacos que han sido estudiados para el tratamiento de nefritis lúpica y que no han mostrado efectos benéficos, como rituximab y ocrelizumab. , 81 ( 2022 ) , pp. 1 Long-term outcomes in LN have clearly improved. GAZYVA ® (obinutuzumab) is a prescription medicine used with the chemotherapy drug, bendamustine, followed by GAZYVA alone for follicular lymphoma (FL) in adults who did not respond to a rituximab-containing regimen, or whose FL returned after such treatment. Obinutuzumab could offer the lupus community an effective new treatment option for controlling this difficult disease that can be associated with high morbidity for individuals living with lupus. Obinutuzumab, a monoclonal antibody that targets the CD20 receptor on B-cells, is Objective: Depleting pathogenic B cells could treat systemic lupus erythematosus (SLE). Proliferative lupus nephritis (LN) is the most common severe organ-threatening manifestation of systemic lupus erythematosus (SLE). We hypothesized that a Type II anti-CD20 mAb with a different mechanism–obinutuzumab (GA101)—could be Jun 11, 2019 · Positive Phase-III-Ergebnisse zu Obinutuzumab zeigen Überlegenheit gegenüber alleiniger Standardtherapie bei Patienten mit Lupus-Nephritis. a phase iii, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of obinutuzumab in patients with systemic lupus erythematosus BackgroundPrevious studies comparing the efficacy and safety of different treatment regimens for lupus nephritis are scarce. Obinutuzumab, a monoclonal antibody that targets the CD20 receptor on B-cells, is currently indicated for the treatment of chronic lymphocytic leukemia and follicular lymphoma in combination with chemotherapy under the brand name Gazyva ®. compared to the control group, obinutuzumab (22. Six of these patients were rituximab refractory and 1 had a response to rituximab but was switched to obinutuzumab because of an adverse reaction. As mentioned above, voclosporin (Lupkynis) targets T cells to reduce inflammation in the kidneys. González-García, G. Sep 27, 2024 · Roche announced positive topline results from the phase III REGENCY study of Gazyva/Gazyvaro (obinutuzumab) in people with active lupus nephritis. Rovin,1 Richard Furie,2 Gustavo Aroca,3 Jay P. The pharma will present these data to the FDA and other global health authorities with the goal of securing approvals in this indication. “I Anca D. The LRA is pleased to share that the U. Ocrelizumab and obinutuzumab, newer CD20-oriented SLE therapies, together with ofatumumab and veltuzumab, are also promising. (Arnold et al. 26. Two-year results from a randomised, controlled study of obinutuzumab for proliferative lupus nephritis. 41608 Lupus nephritis is the name for lupus kidney disease. doi: 10. 4, 5 It is also clear Patients with proliferative lupus nephritis—induction: obinutuzumab versus induction: placebo Table S48. Pendergraft III, 2 Ana Malvar, 5 Brad H. This chapter provides a detailed overview of the discovery and optimization of obinutuzumab in preclinical Novel biologics for lupus nephritis, including obinutuzumab, abatacept, and belimumab, show efficacy within certain time frames. ” Obinutuzumab is a type II engineered humanized monoclonal antibody that’s designed to attach to the CD20 protein found on certain B cells, which Consistent with this hypothesis, a phase 2 study of obinutuzumab in lupus nephritis has met its primary endpoint where the phase 3 study of rituximab did not. Here, we provide a comprehensive review of clinical trials that form the basis for the Kidney Disease: Improving Global Outcomes and EULAR/ERA-EDTA updated guidelines and present day trials that will change the landscape of lupus nephritis therapy in years to come. Sustained depletion up to Week 52 was September 18, 2019. It is a monoclonal antibody target CD-20, which is expressed on the surface of B cells and acts through the cellular cytotoxicity triggers two mechanisms one is Antibody-Dependent Cellular Cytotoxicity (ADCC) and Complement-Dependent Cytotoxicity (CDC). Afimetoran: Etude de phase II, en double aveugle, contre placebo, évaluant l’efficacité et la sécurité d’emploi de BMS-986256 Gazyva®/Gazyvaro® (obinutuzumab) is a Type II engineered humanised monoclonal antibody designed to attach to CD20, a protein found on certain types of B cells. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation to obinutuzumab (Gazyva®) for adults with lupus nephritis – the most common complication of lupus. We hypothesized that a Type II anti-CD20 mAb with a different mechanism–obinutuzumab (GA101)—could be Roche subsidiary Genentech announced on Thursday that Gazyva (obinutuzumab) met its primary efficacy endpoint in the Phase III REGENCY study of lupus nephritis. Depleting pathogenic B cells could treat SLE. (2021) 73:826–36. A. 1 Although promising data are emerging for B-cell-modulating biologics such as belimumab and obinutuzumab,2,3 oral drugs have the advantages of convenience and lower cost. Calcineurin inhibitors (CNIs) have long been used to treat lupus Although other indications do not allow the same degree of tissue sampling as in transplantation, in a recent study of obinutuzumab in lupus nephritis (NOBILITY), efficacy correlated with Hepatitis B infection and reactivation (including fatal cases) have been reported in patients taking obinutuzumab. A clinical trial to look at how well obinutuzumab works in treating people with lupus nephritis and how safe it is (REGENCY) A Study To Evaluate The Efficacy And Safety Of Obinutuzumab In Patients With ISN/RPS 2003 Class III Or IV Lupus Nephritis Access the clinical trial testing the efficacy, safety, and pharmacokinetics of obinutuzumab in adolescent patients with active class III or IV lupus nephritis. 6 to 2. A post hoc analysis of the Genentech Phase 2 NOBILITY trial has shown that obinutuzumab (Gazyva), combined with standard therapies, effectively treats proliferative LN (severe kidney inflammation). Another way to reduce kidney damage is to The NOBILITY (A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Evaluate the Safety and Efficacy of Obinutuzumab in Patients With ISN/RPS 2003 Class III or IV Lupus Nephritis) trial randomized 126 patients Genentech’s Gazyva (obinutuzumab), in Combination With Standard of Care, More Than Doubles the Percentage of Lupus Nephritis Patients Achieving Complete Renal Response, Compared To Standard of Care Alone Lupus nephritis is a severe and potentially life-threatening manifestation of systemic lupus erythematosus resulting from inflammation Abstract. Comparative studies of treatment regimens Obinutuzumab (a rituximab biobetter) is under development for the treatment of systemic lupus erythematosus, hairy cell leukemia, lupus nephritis, graft versus host disease (GVHD), Waldenstrom macroglobulinemia, membranous nephropathy, non-Hodgkin lymphoma, diffuse large B-cell lymphoma, nodal, metastatic hormone refractory (castration resistant, androgen The Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to obinutuzumab (), a CD20-directed cytolytic antibody, for the treatment of adults with lupus nephritis. kidney Lupus nephritis (LN) is a serious kidney complication associated with systemic lupus erythematosus (SLE), marked by the immune system's misdirected attack on kidney tissues, resulting in inflammation and compromised filtration. 1 In lupus nephritis, disease-causing B cells drive persistent inflammation that damages the kidneys. In our study, none of the patients presented side effects with obinutuzumab treatment Obinutuzumab (Gazyva [Genentech, South San Francisco, CA]) (1 with lupus-associated MN and 1 with de novo MN in allograft). Obinutuzumab is a glycoengineered type II CD20 antibodythat has been developed to improve upon the treatment benefits achievedwith rituximab and to address resistance to rituximab therapy, which eventuallydevelops in a large proportion of patients. This condition has the potential to progress to end-stage renal disease in about 20% of patients within a decade of diagnosis. It was highlighted that efficient B cell depletion was clearly associated with the long-standing beneficial effects of obinutuzumab in lupus nephritis patients . 10, 2024 (GLOBE NEWSWIRE) -- While GSK’s Benlysta (belimumab) and Aurinia’s Lupkynis (voclosporin) have been important advances in the treatment arsenal for lupus nephritis (LN B-cell depletion with obinutuzumab for the treatment of proliferative lupus nephritis: a randomised, double-blind, placebo-controlled trial. If you take SAN DIEGO — Obinutuzumab and ianalumab are two promising B-cell depleting therapies on the horizon for lupus, according to data presented at the 2024 Congress of Clinical Rheumatology West. The FDA’s designation aims to speed up the development and review of drugs intended to treat a serious condition “when The benefit of obinutuzumab in lupus nephritis has been described in a published phase 2 randomised controlled trial (Furie et al, 2022) as well as a UK case series in the specific rituximab secondary non-response population proposed. [3] Anifrolumab ist ein humaner monoklonaler Antikörper gegen die Typ-I-Interferonrezeptor-Untereinheit 1 (anti-Typ-1 IFNR), der zur Behandlung von systemischem Lupus erythematodes (SLE) untersucht wurde. The breakthrough designation for treating adult Roche announced this week that the U. Obinutuzumab, a monoclonal antibody that targets the CD20 NEW YORK, Nov. After obinutuzumab, 4/9 patients received 5mg and were in Lupus Low Disease Activity State (LLDAS). In the Background: Lupus nephritis (LN) is the most common severe organ-threatening manifestation of systemic lupus erythematosus. Brunetta,4 Introduction: Systemic lupus erythematosus (SLE) is a complex autoimmune disease, and despite the availability of multiple treatments, striking a balance between long-term efficacy and side effects remains a major clinical challenge. A clinical trial to compare obinutuzumab with placebo in adolescents with lupus nephritis (POSTERITY) A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Obinutuzumab in Adolescents With Active Class III or IV Lupus Nephritis and the Safety and PK of Obinutuzumab in Pediatric Participants. Askanase, MD, MPH, shares potential highlights for the upcoming ACR Convergence 2024 and how excitement is building in the area of lupus therapeutics development, including two phase 3 Standard Dosing Schedule For Follicular Lymphoma Premedication & administration1 • Premedicate before each infusion• Provide prophylactic hydration and antihyperuricemics to patients at high risk of tumor lysis syndrome • Administer only as an intravenous infusion through a dedicated line Loading - Oxford Academic Loading INTRODUCTION Lupus nephritis remains a severe and therapeutically challenging manifestation of systemic lupus erythematosus. Systemic lupus erythematous (SLE) is a complex autoimmune disease characterized by a relapsing-remitting course [1] and a wide spectrum of clinical features: from mild [2] to severe manifestations such as lupus nephritis (LN) [3] and central nervous system involvement [4]. Introduction. Ocrelizumab Gazyva Combo Helps Lupus Nephritis Patients Achieve Response, Trial Data Show Gazyva Combo Helps Lupus Nephritis Patients Achieve Response, Trial Data Show Gazyva (obinutuzumab) in combination with standard-of-care agents significantly increases the percentage of patients with proliferative lupus nephritis achieving complete or partial renal In die Therapie bei systemischem Lupus erythematodes kommt Bewegung – mit dem Interferon-1-Rezeptor-Antikörper Anifrolumab und Obinutuzumab. Calcineurin inhibitors (CNIs) have long been used to treat Lupus nephritis is one of the most severe manifestations of systemic lupus erythematosus, affecting roughly 40% of all lupus patients. This study was undertaken to investigate whether a type II anti-CD20 monoclonal antibody (mAb) with a different mechanism of action, obinutuzumab (GA101), is more effective than a type I anti-CD20 mAb, Genentech, a member of the Roche Group, announced positive topline results from the Phase III REGENCY study of Gazyva® (obinutuzumab) in patients with active lupus nephritis. Two-year results from NOBILITY are reported A potent CD20 targeting mAb, obinutuzumab, had a positive result in a phase 2 randomized trial in 125 patients with lupus nephritis, 155 and case series suggest it could be effective in patients Anca D. 1136/annrheumdis-2021-220920 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] This was a phase 2, randomized, double-blind, placebo-controlled, multi-center study. placebo, combined with mycophenolate mofetil This parallel-group, double-blind, placebo-controlled study will evaluate the efficacy and safety of obinutuzumab versus placebo in participants with active, autoantibody-positive systemic lupus erythematosus (SLE) who are treated with standard-of-care therapy. Food and Drug Administration granted breakthrough therapy designation of obinutuzumab (Gazyva) for lupus nephritis, a major morbidity of systemic lupus erythematosus (SLE). The addition of Pharmaceutical company Roche announced today that the U. AlloNK is a type of therapy made from natural killer (NK) cells, which are part of the immune Nov 10, 2023 · INTRODUCTION. ]. Rovin 6 A global Phase 3 trial, called REGENCY (NCT04221477), aims to confirm the efficacy and safety of Gazyva against a placebo, both given with standard care, in about 252 adults with lupus nephritis. research type. 100 - 107 , 10. The randomized, placebo-controlled, Phase II NOBILITY trial ([NCT02550652][1]) demonstrated superiority of obinutuzumab over placebo for achievement of complete and overall renal responses at Week 52 when added to standard-of-care Phase 3 trial underway into Gazyva as an add-on lupus nephritis treatment. The findings were presented at two meetings this month. Arthritis Rheumatol . Food and Drug allegory - obinutuzumab in patients with systemic lupus erythematosus. What does the study involve? Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by pronounced heterogeneity in autoantibody profiles, organ manifestations, and response to therapy. The authors would like to thank Sangeeta Jayakar for assistance with the immunofluorescence staining. alone, NOBILITY showed that obinutuzumab on a background of standard-of-care therapies improved renal responses through 104 weeks without increasing the frequency of serious adverse events. L’obinutuzumab est un anticorps monoclonal anti-CD20, entièrement humanisé, qui se SAPL-LUPUS: Registre des patients avec un SAPL et/ou un lupus systémique PREPCOV: Etude en vie réelle de l'efficacité d'une exposition préalable à évaluant la sécurité d’emploi et l’efficacité de l’obinutuzumab au cours du lupus systémique . 4, 5 It is also clear Background/Purpose: NOBILITY demonstrated improved renal responses and complete B-cell depletion with the humanized type II anti-CD20 monoclonal antibody obinutuzumab (OBI) compared with placebo (PBO) through 18 months in patients with proliferative lupus nephritis (LN) when added to standard of care therapies [1]. INTRODUCTION. Ross Terres, 2 Elsa Martins, 3 Imran Hassan, 4 Thomas Schindler, 3 Jay Garg, 2 William F. However, depleting B cells in the presence of an inflammatory setting such as lupus is difficult. Patients with proliferative lupus nephritis—induction: dapirolizumab versus induction: placebo Patients with proliferative lupus nephritis—maintenance: hydroxychloroquine, low dose (2 –3mg/kg/d) versus maintenance hydroxychloroquine, high dose (4 –5. After one cycle with obinutuzumab (1 g, day 0, 14), both patients came off dialysis and showed a stable kidney function over a time period of at least 6 months. The first presentation, “ A Phase 2 Randomized, Controlled Study of Obinutuzumab A Study To Evaluate The Efficacy And Safety Of Obinutuzumab In Patients With ISN/RPS 2003 Class III Or IV Lupus Nephritis (REGENCY) Group 2 receive obinutuzumab 1000 mg IV at baseline and Weeks 2, 24, 26, and 52 plus MMF and oral prednisone. In new data from the NOBILITY trial, presented at the American College of Rheumatology (ACR) Convergence 2020, an international team of investigators reported and neuropsychiatric lupus, respectively. 5 mg/day with standard immunosuppressant dosage) . Patient 6 had a partial renal response but required renal transplantation, which was successful. Objectives We set out to Obinutuzumab is a next-generation humanised type-2 anti-CD20 antibody licensed for the treatment of haematological malignancies. 2024 Roche hat positive Gesamtergebnisse der Phase-III-Studie REGENCY zu Gazyva®/Gazyvaro® (Obinutuzumab) bei Patienten mit aktiver Lupus-Nephritis veröffentlicht. Manufacturer advises patients with positive hepatitis B serology should be referred to a liver specialist for monitoring and initiation of antiviral therapy before treatment initiation; treatment should not be initiated in patients A first person has been dosed with the investigational therapy, AlloNK® (also known as AB-101) for treatment of lupus nephritis, (LN, lupus-related kidney disease). 18, 19 Indeed, the glycoengineered Fc region of Obinutuzumab was developed to enhance its binding affinity to the FcγRIII receptor on immune effector cells, thereby augmenting Following obinutuzumab therapy, 5/9 patients had their dose reduced, of whom 4/9 reduced to 5 mg/day and achieved a Lupus Low Disease Activity State (LLDAS; defined as SLEDAI <4 without major organ activity, no new disease activity, physician’s global assessment ≤1 and prednisolone ≤7. Por el contrario, obinutuzumab es un fármaco anti-CD20 que mostró efectividad para el tratamiento de nefritis lúpica y que puede sumarse a las nuevas terapias como una opción Richard Furie, MD, chief of the division of rheumatology with Norwell Health, discusses the results of a phase 2 trial examining obinutuzumab for lupus nephritis. Patient 5 did not respond and required further methylprednisolone and cyclophosphamide at 4 months. Group 2 participants will receive a placebo infusion at their Week 50 visit. Introduction: Systemic lupus erythematosus (SLE) is a multifaceted autoimmune disorder characterized by significant autoantibodies, particularly targeting nuclear antigens. 18, 19 Indeed, the glycoengineered Fc region of Obinutuzumab was developed to enhance its binding affinity to the FcγRIII receptor on immune effector cells, thereby augmenting In a post hoc analysis of the phase 2 NOBILITY trial, researchers found that treatment with obinutuzumab—an antibody that targets a protein expressed on certain immune cells—was superior to placebo for preserving kidney function and preventing flares in patients with lupus nephritis, a kidney condition associated with the autoimmune disease lupus. 1 The data presented here suggest an efficacy of obinutuzumab in different CTD even after failure of rituximab. One patient had cardiac involvement and highly elevated NT- pro-BNP which markedly decreased after treatment with obinutuzumab. 2 We can target an underlying cause of lupus nephritis to help gain better control of the disease Several successful phase 3 trials and the approval of these new therapies in systemic lupus erythematosus (SLE), have resulted in increased interest in drug development in lupus. However, depleting B cells in an inflammatory setting such as lupus is difficult. Unlike rituximab, obinutuzumab has lower SAN DIEGO — Obinutuzumab and ianalumab are two promising B-cell depleting therapies on the horizon for lupus, according to data presented at the 2024 Congress of Clinical Rheumatology West. Consistent with this hypothesis, a phase 2 study of obinutuzumab in lupus nephritis has met its primary endpoint where the phase 3 study of rituximab did not. 5), Despite the improved treatment strategy for lupus nephritis, 22% of patients still develop renal failure at 10 years. Autoimmune Disorder; Lupus Nephritis In a new study, researchers looked at the impact of adding obinutuzumab to the standard of care treatment plan for lupus nephritis (LN, lupus-related kidney disease) to determine if its addition could improve long-term preservation of kidney function with less glucocorticoids use, which can have a variety of side effects from long-term use. The latest trials New York, NY, September 25, 2024 — The Lupus Research Alliance (LRA) and clinical research affiliate Lupus Therapeutics (LT) are excited to share positive news of the Phase 3 REGENCY clinical trial showing benefits of Gazyva ® (obinutuzumab) in treating people with active lupus nephritis (inflammation of the kidney associated with lupus). Keywords: Secondary inefficacy with infusion reactions an Objective: Randomised trials of type I anti-CD20 antibodies rituximab and ocrelizumab failed to show benefit in proliferative lupus nephritis (LN). Time to unfavorable kidney outcome (a composite of treatment failure, doubling of serum Background Secondary inefficacy characterized by infusion reactions and anti-drug antibodies occur in 14% of SLE patients treated with repeat rituximab courses(1). The randomized, placebo-controlled, Phase II NOBILITY trial (NCT02550652) In a new study, researchers looked at the impact of adding obinutuzumab to the standard of care treatment plan for lupus nephritis (LN, lupus-related kidney disease) to determine if its addition could improve long-term preservation of kidney function with less glucocorticoids use, which can have a variety of side effects from long-term use. Before 1980, kidney survival at 5 years was as low as 20%, whereas modern treatments have improved this rate to 80%. 2024. The Lupus Research Alliance (LRA) and clinical research affiliate Lupus Therapeutics (LT) are excited to share positive news of the Phase 3 REGENCY clinical trial showing benefits of Gazyva ® (obinutuzumab) in treating people with active lupus nephritis (inflammation of the kidney associated with Obinutuzumab is a next-generation humanized type-2 anti-CD20 therapy licensed for hematological malignancies which may overcome this issue (2). 1 Despite numerous advances in the treatment of active lupus nephritis, including the regulatory approvals of belimumab in 2020 and voclosporin in 2021, 2, 3 complete renal response (CRR) rates remain low. However, 10% of patients still progress towards end-stage kidney disease, which carries an elevated Improvements in other renal response measures, lupus serology, estimated glomerular filtration rate (eGFR) and proteinuria were greater with obinutuzumab. Comment se déroule l’étude clinique POSTERITY ? Cette étude clinique The work-up for secondary causes of MN was negative except in 2 patients (1 with lupus-associated MN and 1 with de novo MN in allograft). 5 g/kg/d) www. The study demonstrated that a higher percentage of individuals treated with Gazyva, in addition to standard therapies mycophenolate mofetil and glucocorticoids, achieved a A Phase 3 study of Gazyva in lupus nephritis is expected to start next year. 1459241. Cette variabilité de l’expression clinique et de la sévérité explique la nécessité mais aussi la complexité du développement de nouvelles thérapeutiques. The Lupus nephritis is an important cause of both acute kidney injury and chronic kidney disease that can result in end-stage renal disease. We compared obinutuzumab, a humanised Genentech announced positive results from the Phase III study (REGENCY) of Gazyva (Obinutuzumab) for people with active lupus nephritis (LN). Food and Drug Administration (FDA) has granted its antibody-targeting treatment Gazyva (obinutuzumab) the “Breakthrough Therapy Designation” (BTD) for adults with lupus nephritis (LN). This clinical trial is recruiting adolescents who have active lupus nephritis (LN). Seven patients (70%) had received rituximab within a year before receiving obinutuzumab. 2,3 Current standard induction and Obinutuzumab for Proliferative Lupus Nephritis Brad H. In the study, a higher proportion of people treated with Gazyva/Gazyvaro plus standard therapy (mycophenolate mofetil and glucocorticoids) achieved a complete renal response (CRR) at 76 weeks Depleting pathogenic B cells could treat SLE. 1016/j. In the U. Who can participate? People with lupus nephritis between the age of 18-75 years. These data were detailed in the study, “ Kidney Outcomes and Preservation of Kidney Function With Obinutuzumab in Patients With Lupus Nephritis: A Post Hoc Analysis of the NOBILITY Trial,” published in the journal Arthritis & Rheumatology. This chapter provides a detailed overview of the discovery and optimization of obinutuzumab in Positive topline results were announced from a phase 3 study of obinutuzumab in patients with lupus nephritis. 3389/fimmu. 2 We can target an underlying cause of lupus nephritis to help gain better control of the disease Obinutuzumab is a glycoengineered type II CD20 antibodythat has been developed to improve upon the treatment benefits achievedwith rituximab and to address resistance to rituximab therapy, which eventuallydevelops in a large proportion of patients. ACKNOWLEDGMENTS. However, many patients remain refractory to currently available therapies and suffer from drug toxicities. With the introduction of cyclophosphamide and mycophenolate mofetil, outcomes have dramatically improved. Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease characterized by a wide spectrum of clinical, laboratory and immunological manifestations. 1136/annrheumdis-2021-220920 Bibliographie Néphrologie Clinique B-cell depletion with obinutuzumab for the treatment of proliferative lupus nephritis: a randomised, double-blind, placebo-controlled trial Richard A Furie 1, Gustavo Aroca 2 , Matthew D Cascino SUN-374 B-CELL DEPLETION AND RESPONSE IN A RANDOMIZED, CONTROLLED TRIAL OF OBINUTUZUMAB FOR PROLIFERATIVE LUPUS NEPHRITIS March 2020 Kidney International Reports 5(3):S352 DOI:10. B-cell depletion with obinutuzumab for the treatment of proliferative lupus nephritis: a randomised, double-blind, placebo-controlled trial Ann Rheum Dis. Editing and writing assistance for this article was provided After obinutuzumab, 4/9 patients received 5mg and were in Lupus Low Disease Activity State (LLDAS). Its effects, in Autoimmune Disorder Lupus Nephritis Healthy Volunteers A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Obinutuzumab in Chinese Patients With ISN/RPS 2003 Class III or IV Lupus Nephritis Trial Status Trial Runs In Trial Identifier Recruiting 1 Countries YA42816 The source of the below information is the In a randomized, double-blind, placebo-controlled trial among adult patients with lupus nephritis, obinutuzumab was administered as a blinded IV infusion of 1000 mg on day 1 and weeks 2, 24, and 26. Lupus results when abnormal immune B-cells produce self These findings are consistent with previous studies investigating the efficacy of Obinutuzumab for various indications, including lupus nephropathy 16, 35, 36 and MN. Gazyva is an engineered humanized monoclonal antibody designed to attack CD20, a protein found on certain types of B cells that cause Obinutuzumab is a type II anti- CD20 antibody that results in greater B- cell depletion than rituximab; in a preclinical study, obinutuzumab was shown to be more effective Obinutuzumab is a type II anti-CD20 antibody that results in greater B-cell depletion than rituximab; in a preclinical study, obinutuzumab was shown to be more effective than rituximab in a murine model of lupus nephritis. Obinutuzumab (Gazyva, Roche) is an FDA-approved treatment for chronic lymphocytic leukemia. Methods: Post hoc analyses of the phase II NOBILITY trial were performed. 5 months), abatacept-10mg (17. Arthritis Rheumatol 72 EXTON, PA, Oct. ’ Both medical subject headings (Mesh) terms and free terms were searched to ensure a broad and inclusive search (Supplementary Table S1). oral drugs have the advantages of convenience and lower cost. Purpose of review: The approval of belimumab and anifrolumab has expanded the scope of treatment for systemic lupus erythematosus (SLE) patients. Garg,4 Analía Alvarez,5 Hilda Fragoso-Loyo,6 Elizabeth Zuta Santillán,7 Paul G. The trial included patients with active class III/IV lupus nephritis who received obinutuzumab vs. 1002/art. 3 months) demonstrated significant superiority (HR ranged from 1. Among the novel biological agents for lupus nephritis, renal response within a specific therapeutic time window improves with obinutuzumab, abatacept, and belimumab, investigators report. full title. 10, 2019 /PRNewswire/ — The Lupus Research Alliance (LRA) is pleased to acknowledge positive results presented by Genentech at the American Society of Nephrology (ASN) and the 2019 ACR/ARP Annual Meeting showing the effectiveness of obinutuzumab (), a type I anti-CD20 monoclonal antibody, in the Phase 2 NOBILITY trial for the most severe form This July, study results from the phase 3 REGENCY trial, which evaluated patients with active lupus nephritis treated with obinutuzumab (n=271), were reported (NCT04221477). 5 This study was double blind and placebo New research finds that both Gazyva® (obinutuzumab) and Rituxan® (rituximab) are effective in treating lupus during the early stages of disease, but Gazyva may promote better treatment outcomes overall. [33,34] and ocrelizumab failed to show significant benefit in lupus nephritis, obinutuzumab, a humanized type II anti-CD20 monoclonal antibody that induces more potent B-cell depletion, has been Objective: To determine whether adding obinutuzumab to standard-of-care lupus nephritis (LN) therapy could improve the likelihood of long-term preservation of kidney function and do so with less glucocorticoids. Background/Purpose: Lupus nephritis (LN) is the most common severe organ-threatening manifestation of systemic lupus erythematosus (SLE). 09. rolhy xqih fnxqh yhqtr avoa zxtwokmcr vwkizos gcy uada ioibk