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

Clinical adverse events to voclosporin: a real-world drug safety study based on FDA Adverse Event Reporting System. (PubMed, Clin Exp Rheumatol) - "The present research provides a significant assessment of the postmarketing safety profile of voclosporin. However, additional studies are needed to corroborate and solidify these observations. Clinicians are advised to remain highly vigilant about the potential AEs associated with voclosporin and to carefully consider the appropriate dosing regimens when utilising this medication in clinical practice."

Adverse events • Journal • Real-world evidence • Cardiovascular • Dermatology • Gastroenterology • Gastrointestinal Disorder • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology

Precision Editing of Cyclophilin A Generates Cyclosporine and Voclosporin Resistant Cellular Therapies. (PubMed, bioRxiv) - "This report of site-specific CypA modification offers a promising avenue for developing next-generation IECs that should function effectively in patients receiving CsA/VCS and thus expand applications for adoptive cell therapies in multiple clinical settings. CRISPR editing of the last exon of PPIA retains CypA expression but with an altered C-terminus that disrupts CsA and VCS interactions PPIA Δ C immune effector cells demonstrate retained proliferation and function in the presence of CsA and VCS."

IO biomarker • Journal • Immunology • Transplantation • PPIA

Management of Refractory Lupus Nephritis Based on New Guideline: Glomerular and Tubulointerstitial Disorders (KSN 2025) - "Promising options include obinutuzumab, anifrolumab, belimumab, and voclosporin. In this lecture, we will review the key updates in the 2024 KDIGO lupus nephritis guidelines and examine the clinical evidence supporting these changes. We will also explore real-world cases of refractory lupus nephritis and discuss practical examples of how the aforementioned therapies are being applied in clinical practice."

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

LUPKYNIS Drug-use Results Survey (clinicaltrials.gov) - P=N/A | N=400 | Not yet recruiting | Sponsor: Otsuka Pharmaceutical Co., Ltd.

New trial • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology

LUPKYNIS Drug-use Results Survey (clinicaltrials.gov) - P=N/A | N=400 | Recruiting | Sponsor: Otsuka Pharmaceutical Co., Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology

Development and Application of a Senolytic Predictor for Discovery of Novel Senolytic Compounds and Herbs. (PubMed, Molecules) - "In an experimental screening of predicted compounds, panaxatriol was found to exhibit senolytic activity on the etoposide-induced senescence of the IMR-90 cell line. Additionally, voclosporin was found to extend the lifespan of C. elegans more effectively than metformin, demonstrating the value of our model for drug repurposing. This study not only provides an efficient framework for discovering novel senolytic agents, but also highlights the predicted novel senolytic compounds and herbs as valuable starting points for future research into senolytic drug development."

Journal

A Prospective Observational Registry of Patients Treated With LUPKYNIS® (Voclosporin) in the US (clinicaltrials.gov) - P=N/A | N=229 | Completed | Sponsor: Aurinia Pharmaceuticals Inc. | Recruiting ➔ Completed | Trial completion date: Jun 2030 ➔ Jan 2025 | Trial primary completion date: Nov 2026 ➔ Jan 2025

Trial completion • Trial completion date • Trial primary completion date • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology

Voclosporin-induced gingival enlargement: A case report. (PubMed, Clin Adv Periodontics) - "The gingiva (gums) is often a site in the mouth where changes or reactions can occur in response to certain systemic medications. Some drugs, particularly those used to treat autoimmune conditions or following organ transplants, can cause the gums to grow excessively, a condition known as drug-induced gingival enlargement (also known as gingival overgrowth). In this report, we document the case of a 27-year-old woman with lupus nephritis who developed gingival enlargement after starting a medication called voclosporin. This drug is a newer treatment option for lupus nephritis, but until now had not been linked to gingival enlargement. The patient experienced significant gum swelling, bleeding, and pain, making it difficult for her to eat. After trying nonsurgical treatments with limited success, and given her objection to surgical therapy, the medication was gradually stopped in consultation with her physician. The enlargement of the gums significantly improved once the..."

Journal • Dental Disorders • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Pain • Periodontitis • Systemic Lupus Erythematosus • Transplantation

Voclosporin: A comprehensive review of its role as a novel calcineurin inhibitor in the management of systemic lupus erythematosus. (PubMed, Medicine (Baltimore)) - "Voclosporin offers superior efficacy and safety compared to traditional CNIs for managing lupus nephritis, with predictable dosing and a favorable side effect profile. Continued research is needed to optimize voclosporin's use and support personalized medicine approaches."

Journal • Cardiovascular • Dyslipidemia • Glomerulonephritis • Hypertension • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Systemic Lupus Erythematosus

VOCAL-EXT: Long-Term Voclosporin Treatment in Adolescent and Pediatric Subjects With Lupus Nephritis (clinicaltrials.gov) - P3 | N=40 | Enrolling by invitation | Sponsor: Aurinia Pharmaceuticals Inc. | Trial completion date: Sep 2026 ➔ Jun 2029 | Trial primary completion date: Jun 2026 ➔ Dec 2028

Trial completion date • Trial primary completion date • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Pediatrics

VOCAL: Voclosporin in Adolescent and Pediatric Subjects With Lupus Nephritis (clinicaltrials.gov) - P3 | N=40 | Recruiting | Sponsor: Aurinia Pharmaceuticals Inc. | Trial completion date: Jan 2025 ➔ Jun 2028 | Trial primary completion date: Dec 2024 ➔ Dec 2027

Trial completion date • Trial primary completion date • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Pediatrics

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

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

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

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

An 18 month outcome survey of the utilisation, accessibility and value of the Eastern Network for Kidney Inflammatory Disease (ENKID) virtual multidisciplinary team meeting (MDT). (UKKW 2025) - "34 responders reported receiving HCD approval for avacopan (74%), rituximab (56%), targeted-release budesonide (38%), belimumab (29%) and voclosporin (26%) (Figure 2). Overall 15 centres with 75 health care professional attendees suggests high accessibility; however, ongoing work will describe geographical access to ENKID and HCD use across the East of England, to ensure that discrepancies in access are identified and resolved. With further HCDs on the horizon for autoimmune kidney diseases, robust services and networks such as ENKID are essential to ensure specialist advice and equity of access to HCDs."

ANCA Vasculitis • Glomerulonephritis • Immunology • Inflammation • Inflammatory Arthritis • Nephrology • Renal Disease • Rheumatology • Vasculitis

The Eastern Network Kidney Inflammatory Disease (ENKID) MDT at 18 Months: Advancing Access to High-Cost Drugs, Clinical Trials, and Complex Case Management in renal autoimmunity. (UKKW 2025) - "A HCD (avacopan, belimumab, voclosporin, TR budesonide, rituximab) was endorsed in 75% of patient cases presented and alternatives recommended in 25%. High attendance and case load underscore the unmet need for this specialist service aligning with the UK government’s mandate for rare autoimmune disease. We describe integration of this novel network within the existing renal regional network structure in the EOE, providing governance, training, access to HCDs and patient outcome reporting."

Clinical • ANCA Vasculitis • Chronic Kidney Disease • Complement-mediated Rare Disorders • Focal Segmental Glomerulosclerosis • Glomerulonephritis • IgA Nephropathy • Immunology • Infectious Disease • Inflammation • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Rare Diseases • Renal Disease • Rheumatology • Vasculitis

Enlight-LN Registry: baseline demographics and clinical characteristics of an initial cohort of patients treated with voclosporin for lupus nephritis in the United States (UKKW 2025) - "In the AURORA 1 and AURORA 2 studies, adding voclosporin to mycophenolate mofetil (MMF) and low-dose glucocorticoids led to significantly earlier and greater reductions in proteinuria while maintaining stable estimated glomerular filtration rate (eGFR) for up to 3 years...A total of 107 patients were on concomitant immunosuppression at voclosporin initiation (most commonly, antimalarials, 72.4%; MMF/mycophenolate sodium, 70.7%; belimumab, 13%)... Baseline data on this initial cohort of patients are reflective of the larger LN population in the US, including high percentages of Black and Hispanic and/or Latino patients. Enrollment of additional patients and ongoing data collection will provide valuable insight into the real-world utilization of voclosporin."

Clinical • Glomerulonephritis • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Renal Disease

Rates of sustained complete renal-response with long-term use of voclosporin in AURORA 2 (UKKW 2025) - "Significantly more patients treated with VCS in combination with MMF and low-dose glucocorticoids (GCs) achieved CRR compared to patients in the control arm treated with mycophenolate mofetil (MMF) and low-dose GCs (41% vs 23%, odds ratio [OR] 2.65, 95% confidence interval [CI] 1.64-4.27, p<0.0001). SCRR is a novel endpoint that can be leveraged to illustrate disease trajectory of LN and treatment efficacy. Consistent with using CRR as an efficacy endpoint in AURORA 1, more VCS- than control- treated patients achieved SCRR, despite nearly 40% of the analyzed study population being ineligible due to the voluntary nature of AURORA 2 participation. The stringency and potential utility of this new endpoint require further exploration."

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

Validity, reliability and responsiveness of Lupus Impact Tracker and LupusPRO: AURORA Trial (UKKW 2025) - "Voclosporin used in addition to mycophenolate mofetil and low dose oral steroids in patients with active lupus nephritis (LN) was found to be superior to placebo in Phase 3, global, double blind, randomized control trial (AURORA 1). both LIT and LupusPRO show good psychometric properties in this clinical trial, including responsiveness. LIT is short, while LupusPRO is comprehensive. For clinical trials, LIT or LupusPRO HRQOL domains inclusion may be more apt to capture proximal effects of the disease and the proposed intervention."

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

Disease targeting properties of voclosporin in renal transplant and lupus nephritis patients (UKKW 2025) - "VCS does not require therapeutic drug monitoring, and is associated with improved glucose, lipid and electrolyte profiles compared to tacrolimus and cyclosporine. The larger peripheral volume of distribution indicates selective peripheral tissue uptake of VCS in patients with renal transplant and LN. This is consistent with immunosuppressive activity of VCS in targeted organs relative to blood circulation. The low blood levels of VCS are consistent with the safety profile of VCS compared to other calcineurin inhibitors."

Clinical • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Transplantation

Immunologic changes over time in repeat kidney biopsies from the AURORA studies of voclosporin in lupus nephritis (UKKW 2025) - "CD34 and Ki67, which have been implicated in tissue regeneration and healing in glomerulonephritides, showed significantly higher expression in repeat biopsies of patients with LN treated with immunosuppression during the AURORA trials. The lack of difference within each treatment group may indicate a lack of concordance between clinical response and immunological landscape but may also be reflective of the small sample size. The potential utility of CD34 and Ki67 as biomarkers of response requires further investigation"

Biopsy • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Renal Disease • CD34

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