Lupkynis (voclosporin) / Aurinia Pharma, Otsuka - LARVOL DELTA

Reply to: "Current Use of PBPK Modeling in New Medicinal Product Approvals at EMA: A Clinical Appraisal of Voclosporin in Lupus Nephritis". (PubMed, Clin Pharmacol Ther) - No abstract available

Journal • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology

PREGNANCY OUTCOMES IN PATIENTS EXPOSED TO VOCLOSPORIN: A SUMMARY OF AVAILABLE DATA FROM CLINICAL TRIALS AND POST-MARKETING SOURCES (EULAR 2025) - P2, P3 | "Therapeutic agents including mycophenolate mofetil (MMF), commonly used in LN, have also been linked to birth defects and pregnancy loss. Active LN in pregnancy is associated with an increased risk of adverse maternal and fetal outcomes, and observations from this limited cohort reflect the overall challenges faced by female patients of child-bearing age with active LN. The limited data presented here are insufficient to draw conclusions regarding the use of voclosporin during pregnancy, and additional research is needed to better characterize maternal and fetal outcomes following voclosporin exposure."

Clinical • P4 data • Cardiovascular • Dermatology • Glomerulonephritis • Gynecology • Hypertension • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Ocular Inflammation • Ophthalmology • Psoriasis • Systemic Lupus Erythematosus • Uveitis

Achievement of Proteinuria Targets ≤0.4 g/g in Lupus Nephritis: A Post Hoc Analysis of the AURORA 1 Study of Voclosporin (EULAR 2025) - "The 52-week, Phase 3 AURORA 1 study showed that the addition of voclosporin to low-dose glucocorticoids and mycophenolate mofetil (MMF) led to significantly greater and earlier reductions in proteinuria compared to treatment with low-dose glucocorticoids and MMF alone [7]...Participants were randomized to either voclosporin (23.7 mg) or matching placebo (control) twice daily, in combination with MMF (target 2 g/day) and low-dose glucocorticoids (intravenous methylprednisolone on Days 1 and 2 [total 1 g], followed by oral prednisone at a starting dose of 20-25 mg/day, tapered to ≤2.5 mg/day by Week 16)... Nearly half of the AURORA 1 population achieved a UPCR ≤0.4 g/g at least once during the 52-week study, surpassing treatment targets recommended by current guidelines for the management of LN. A greater proportion of participants treated with voclosporin achieved UPCR ≤0.4 g/g and did so significantly earlier than control-treated participants, with comparable rates of..."

Retrospective data • Chronic Kidney Disease • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Renal Disease

Post-marketing safety surveillance of voclosporin: an observational, pharmacovigilance study leveraging faers database study on the safety of voclosporin. (PubMed, Front Pharmacol) - "Nearly one-third of the adverse events occurred within the first month after voclosporin initiation, with a median onset time of 99 days. This study clarified the characteristics of voclosporin-related adverse drug reactions, providing strong support for clinical monitoring and risk identification of voclosporin."

Adverse events • Journal • P4 data • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Respiratory Diseases

Current Use of Physiologically-Based Pharmacokinetic (PBPK) Modeling in New Medicinal Product Approvals at EMA: A Clinical Appraisal of Voclosporin in Lupus Nephritis. (PubMed, Clin Pharmacol Ther) - No abstract available

European regulatory • Journal • PK/PD data • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology

Real-world effectiveness and safety of voclosporin in the treatment of lupus nephritis with poor prognostic clinical and histological factors (ERA 2025) - "For the treatment of the current LN episode, before starting VCS, one patient had been treated with a combination of mycophenolate mofetil (MMF) and tacrolimus; another had received cyclophosphamide, MMF, tacrolimus, belimumab, and rituximab; a third had received MMF, tacrolimus, and rituximab; while the remaining two patients started VCS immediately after cyclophosphamide (ELNT schedule) as first-line therapy due to poor prognostic histological criteria. At the time of VCS initiation, all patients were on hydroxychloroquine, and three were receiving prednisone (median: 5 mg/day); three patients were switched from MMF and tacrolimus to MMF and VCS, while the remaining two started VCS immediately after cyclophosphamide as first-line therapy... VCS was effective, in the short term, for optimizing treatment in LN patients with incomplete renal remission despite treatment or with poor prognostic histological factors, in real-world settings and with a good safety and..."

Clinical • Real-world • Real-world effectiveness • Real-world evidence • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology

Voclosporin Overdose-Induced Peroxisomal Structural Changes and AKI Are Prevented by Renal Indole Detoxifier, INMT. (PubMed, J Am Soc Nephrol) - "Inmt overexpression in proximal tubules prevented high-dose voclosporin-induced structural changes and AKI."

Journal • Acute Kidney Injury • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Renal Disease • CAT

Cost-effectiveness analysis of voclosporin vs mycophenolate or belimumab in the treatment of patients with lupus nephritis from the Spanish National Healthcare System perspective (ERA 2025) - P3 | "This study aims to estimate the cost-effectiveness of VCS in combination with mycophenolate mofetil (MMF) vs MMF alone or vs belimumab (BEL) in combination with MMF or cyclophosphamide (CYC), for Spanish patients with LN III-V (and mixed classes) from the perspective of the Spanish National Health System (NHS). In the current situation, the use of VCS could provide more health benefits and cost-savings for the Spanish NHS. Even if BEL price was heavily reduced, VCS would still be a cost-effective intervention for treatment of patients with LN III-IV (and mixed classes)."

Clinical • Cost effectiveness • HEOR • Chronic Kidney Disease • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology

Combination Therapy With Voclosporin and Anifrolumab in Two Patients With Lupus Nephritis and Discoid Lupus Erythematosus. (PubMed, Cureus) - "Therefore, it is critical to identify safe targets for lupus disease activity, minimizing drug toxicity and preventing damage accrual. We present two cases with disease features of discoid lupus erythematosus (DLE) and lupus nephritis (LN), who were treated safely and successfully with Voclosporin and Anifrolumab, resulting in disease remission without the use of oral steroids."

Journal • Discoid Lupus Erythematosus • Glomerulonephritis • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Systemic Lupus Erythematosus

Beneficial effects of voclosporin on reducing proteinuria in lupus nephritis and extrarenal effects in SLE: insights form a small cohort with limited follow-up (ERA 2025) - "Treatments, including corticosteroids, rituximab, and cyclophosphamide, were recorded...One patient presented gingival hyperplasia remembering some patients under cyclosporine which has been controlled with mouth hygiene without voclosporin withdrawal and other patient presented a rash in the hip region which voclosporin collaborated in its improvement... Our preliminary findings suggest that voclosporin is effective, safe and valuable and provides a prompt improvement in proteinuria and serologic profile with extrarenal benefits in some cases, especially valuable in refractory patients. Further large-scale studies are needed to determine the long-term efficacy and safety and identify subgroups of patients who may benefit the most from it. Even further, despite its posology, patients maintained good compliance with voclosporin."

Cardiovascular • Diabetes • Glomerulonephritis • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Lupus Nephritis • Metabolic Disorders • Nephrology • Pulmonary Arterial Hypertension • Renal Disease

ISS1.11 Multi-target treatments and a multidisciplinary approach: How they can improve care for patients with lupus nephritis (ERA 2025) - "The approval of belimumab and voclosporin represents a milestone in the management, and other substances such as obinutuzumab have met the primary endpoint of their approval trial and will likely be marketed soon...Management issues encountered by other specialities such as rheumatologists or dermatologists will be outlined and specific therapies approved for non-renal SLE, such as anifrolumab, will be discussed in this context.Besides treatment of active disease ("remission induction"), long-term prescription of immunosuppression is reality...While such an approach is invasive and often disregarded by affected patients, our symposium will outline that this is an essential point moving forward in the individualisation of therapy.In summary, relevant points for nephrologists are tackled from different perspectives in our symposium. These include the implementation of novel therapies in the management of SLE and LN, when referral to other specialities needs to be..."

Clinical • Chronic Kidney Disease • Fatigue • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Renal Disease • Rheumatology • Systemic Lupus Erythematosus

Effect of long-term voclosporin treatment on renal histology in patients with active lupus nephritis with repeat renal biopsies. (PubMed, Arthritis Rheumatol) - "Outcomes from this small subgroup show exposure to study treatment was not associated with nephrotoxicity based on histopathologic evaluation after 18 months. These data are reassuring and further contribute to the safety profile of voclosporin for the treatment of adults with active LN."

Journal • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology

Voclosporin nephrotoxicity: a myth debunked? (PubMed, Arthritis Rheumatol) - No abstract available

Journal

Specialists Eye Gazyva as a New Option for Lupus Nephritis, but ACR Guidelines Favor Benlysta and Lupkynis for Upfront Use, According to Spherix Global Insights (GlobeNewswire) - "The American College of Rheumatology’s (ACR) newly updated treatment guidelines for lupus nephritis (LN) have led specialists to reconsider their treatment approaches, particularly around the use of triple therapy and the potential future role of Roche/Genentech’s Gazyva (obinutuzumab), which is expected to receive FDA approval for LN later this year.... The ACR conditionally recommends triple therapy—including glucocorticoids, mycophenolate mofetil (MMF) or cyclophosphamide, and either Benlysta or a calcineurin inhibitor (CNI)—for patients who are newly diagnosed, flaring, or have active Class III or IV ± V disease. For patients presenting with high levels of proteinuria (≥3 g/g), the ACR recommends triple therapy that includes a CNI, such as Lupkynis....The guidelines also address patients with pure Class V disease, recommending first-line triple therapy that includes a CNI rather than Benlysta in patients with proteinuria ≥1 g/g."

Clinical guideline • Lupus Nephritis

Voclosporin promotes neurological function recovery by inhibiting inflammation and maintaining blood-brain barrier integrity following rtPA reperfusion after MCAO in mice. (PubMed, Inflammopharmacology) - "By Evans blue extravasation assay and cerebral water content measurement, it was found that voclosporin could improve BBB injury and reduce brain edema caused by rt-PA. The ELISA and immunofluorescence experiments further proved that voclosporin can reduce the expression of IL-1β/TNF-α, increase the expression of IL-10/IL-4, and protect the integrity of the BBB by promoting microglia/macrophage to M2 type polarization, providing new thinking for clinical rtPA combined therapy to alleviate BBB damage."

Journal • Preclinical • Cardiovascular • CNS Disorders • Hematological Disorders • Inflammation • Ischemic stroke • IL10 • IL1B • IL4 • TNFA

The kidney injury biomarker profile of patients with lupus nephritis remains unchanged with the second-generation calcineurin inhibitor voclosporin. (PubMed, Front Nephrol) - P3 | "Samples were analyzed from a cohort of patients in AURORA 1 treated with voclosporin (23.7 mg twice daily, n=57) or placebo (n=59) in combination with mycophenolate mofetil (MMF) and low-dose glucocorticoids, including in a subgroup of patients that experienced a ≥30% decline from baseline in estimated glomerular filtration rate (voclosporin, n=26; placebo, n=20). These findings further support the safety of voclosporin for the treatment of LN in adult patients. ClinicalTrials.gov , identifier NCT03021499; EudraCT, identifier 2016-004045-81."

Biomarker • Journal • Fibrosis • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Renal Disease • KIM1 • TGFB1

Kidney transplantation in Lupus Nephritis: a comprehensive review of challenges and strategies. (PubMed, BMC Surg) - "RECENT FINDINGS: Advancements in immunosuppressive therapies, including calcineurin inhibitors, Voclosporin, and biologic agents such as belimumab, have significantly improved LN management. Current guidelines emphasize the importance of achieving disease quiescence before transplantation, while new evidence supports the benefits of preemptive transplantation and personalized immunosuppressive regimens in improving patient and graft survival. This review highlights the latest evidence and strategies for optimizing kidney transplantation outcomes in LN patients, focusing on timing, immunosuppression, and disease monitoring."

Journal • Review • Chronic Kidney Disease • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Systemic Lupus Erythematosus • Transplantation

Baseline Demographics, Clinical Characteristics, and Medical History of an Initial Cohort of Patients Receiving Voclosporin for Lupus Nephritis in the Enlight-LN Registry (NKF-SCM 2025) - "Common antihypertensives used at baseline included calcium channel blockers (21.1%), diuretics (20.3%), and beta blocking agents (13.8%); 15.4% of patients were on a lipid-modifying agent.Conclusion Baseline data on this initial cohort of patients are reflective of the larger LN population in the US and provide an initial understanding of the use of voclosporin in the real-world. Enrollment of additional patients and ongoing data collection will provide further valuable insight into the real-world utilization of voclosporin."

Clinical • Cardiovascular • Dyslipidemia • Glomerulonephritis • Hypertension • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology

A focused report on IFN-1 targeted therapies for lupus erythematosus. (PubMed, Expert Opin Investig Drugs) - "Despite these challenges, anifrolumab, voclosporin, and belimumab were approved by FDA...This review summarizes the clinical trial outcomes of four upcoming medications targeting cytokine activity: Litifilimab showed a 7-point reduction in CLASI-A in its phase II trial. Daxdilimab was unsuccessful in its phase II trial...Anifrolumab binds to the IFN-I receptor, blocking the activity of all IFN-Is, and deucravacitinib reduces IFN-I by inhibiting TYK2, thereby interfering with downstream signaling. Therapies that target IFN-I represents a promising class of medications for SLE patients."

Journal • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • TYK2

Aurinia Pharmaceuticals Reports Financial Results for the Three and Twelve Months Ended December 31, 2024 and Provides Update on Recent Corporate Progress (Businesswire) - "For the three months ended December 31, 2024, net product sales of LUPKYNIS, the first FDA-approved oral therapy for the treatment of adult patients with active lupus nephritis, were $57.6 million, up 36% from $42.3 million in the same period of 2023...For the twelve months ended December 31, 2024, net product sales were $216.2 million, up 36% from $158.5 million in 2023...Aurinia expects to report initial results from its Phase 1 study of AUR200 in the second quarter of 2025."

New P1 trial • Sales • Immunology • Lupus Nephritis

Advances in Targeted Therapy for Systemic Lupus Erythematosus: Current Treatments and Novel Approaches. (PubMed, Int J Mol Sci) - "This review examines the current evidence for biological therapies in SLE, including the anti-B cell activating factor antibody belimumab; the type I interferon receptor antagonist anifrolumab; the novel calcineurin inhibitor voclosporin; and rituximab, which targets CD20 on B cells. Recent advances in biomarker research, including interferon signatures and transcriptomic profiles, may facilitate patient stratification and treatment selection. This review offers insights into current and future treatment strategies for patients with SLE by analyzing clinical trial results and recent immunological findings."

Journal • Review • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • IFNAR2

Ten tips in lupus nephritis management. (PubMed, Clin Kidney J) - "Effective therapeutic options continue to increase, such as belimumab (a monoclonal antibody that inhibits B-cell activating factor, BAFF) and voclosporin (a calcineurin inhibitor) which have obtained regulatory approval in U.S.A. Ironically, the increasing therapeutic options have resulted in uncertainties in deciding which medication, and which treatment regimen, is best for a patient. In this context, one needs to take into consideration the distinct characteristics and the risk profile of each patient, and adopt a holistic and long-term perspective, so that treatment can be personalized to achieve favourable clinical outcomes."

Journal • Review • Acute Kidney Injury • Chronic Kidney Disease • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Renal Disease • Systemic Lupus Erythematosus

The Role of Sodium-Glucose Co-Transporter-2 (SGLT-2) Inhibitors in Treating Lupus Nephritis: A Systematic Review. (PubMed, Cureus) - "Currently, the medications that are being utilized for the treatment of lupus nephritis (LN), include azathioprine, hydroxychloroquine, cyclophosphamide, belimumab, voclosporin, tacrolimus, mycophenylate, and rituximab...SGLT-2 inhibitors show potential benefits beyond glycemic control. However, due to the novelty of this treatment and the limited studies completed, further testing is required to analyze its true effectiveness in LN."

Journal • Review • Chronic Kidney Disease • Fatigue • Glomerulonephritis • Immunology • Inflammation • Inflammatory Arthritis • Lupus • Lupus Nephritis • Musculoskeletal Pain • Nephrology • Pain • Renal Disease • Rheumatology • Systemic Lupus Erythematosus

New Treatment Regimens, New Drugs, and New Treatment Goals for Lupus Nephritis. (PubMed, J Clin Med) - "With the introduction of cyclophosphamide and mycophenolate mofetil, outcomes have dramatically improved...These agents include belimumab, voclosporin, and obinutuzumab, among others...However, determining which patients would benefit the most from novel agents or combined drug regimens and whether these drugs might serve as an alternative to current remission-induction drug regimens rather than as add-on therapies remain unresolved issues. In this review, we will explore the current evidence regarding the efficacy of novel agents."

Journal • Review • Chronic Kidney Disease • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Renal Disease • Systemic Lupus Erythematosus

Exploring potential drug targets for SLE through Mendelian randomization and network pharmacology. (PubMed, PLoS One) - "Our integrative analysis suggested that levels of circulating PPP3CA; PPP3R1 had causal effects on SLE risk and served as potential treatment targets. Moreover, this study provides new evidence for Voclosporin as an SLE treatment through Mendelian randomization and Network pharmacology, and warrants further clinical investigation."

Journal • Observational data • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • ICAM1 • PACERR • PPP3CA • PPP3R1 • PTGS2 • SIRT1