Lupkynis achieved significantly higher renal response in lupus nephritis patients with high proteinuria compared to patients treated with MMF and low dose steroids alone
Aurinia Pharmaceuticals Inc. announced the results of a post-hoc, pooled analysis of the Phase II AURA-LV (NCT02141672) and Phase III AURORA 1 (NCT03021499) studies, which found that Lupkynis with mycophenolate mofetil (MMF) and low-dose steroids resulted in earlier and greater reductions in proteinuria in lupus nephritis (LN) patients with high proteinuria across biopsy classes, races, and ethnicities
These data were presented at the European Congress of Rheumatology, EULAR 2023, in Milan, Italy.
Consistent with results from the overall pooled study population, patients with urine protein creatinine ratio (UPCR) greater than 2 g/g at baseline treated with Lupkynis achieved significantly higher renal response rates than patients treated with MMF and low-dose steroids alone, regardless of baseline demographics or clinical characteristics.
“Proteinuria is a common manifestation of LN that can lead to progressive kidney damage. Early reductions in UPCR have been shown to be predictive of improved long-term outcomes in LN. Yet, there remains the need for safe and effective therapies for patients with high proteinuria, especially given that monoclonal antibody therapies have demonstrated limited efficacy in LN patients with moderate to high proteinuria. These findings for voclosporin, a novel calcineurin inhibitor, are clinically relevant and can help improve renal outcomes for LN patients,” said lead study author Emily Littlejohn, D.O., M.P.H., Cleveland Clinic Main Campus, Rheumatologic and Immunologic Disease, Cleveland, Ohio.
About the Analysis: To further characterize the efficacy and safety of voclosporin in patients with high proteinuria, outcomes were analyzed in various subpopulations of patients with UPCR greater than 2 g/g at baseline using the pooled dataset from the Phase II AURA-LV and Phase III AURORA 1 studies. Both studies enrolled patients with biopsy-proven LN (Class III, IV, or V ± III/IV) within 6 months (or up to 2 years in AURORA 1) and proteinuria ?1.5 g/g (?2 g/g for Class V). Patients were randomized to voclosporin (23.7 mg BID) or placebo and treated for up to one year (48 weeks in AURA-LV and 52 weeks in AURORA 1). All patients received MMF and low-dose steroids. Protocol-defined glucocorticoid taper included intravenous methylprednisolone on Days 1 and 2. Oral glucocorticoid was initiated on Day 3 with 20-25 mg/day prednisone and tapered to a target dose of 2.5 mg/day at Week 16 and thereafter.
For the analysis, complete renal response (CRR) rates were evaluated in patients with baseline UPCR greater than 2 g/g. CRR was defined as UPCR less than 0.5 g/g with stable renal function, low-dose steroids, and no rescue medication. Subgroup analyses were based on sex, age, race, ethnicity, biopsy class, and estimated glomerular filtration rate (eGFR) at baseline. Adverse events (AEs) and mean eGFR levels over time were also assessed. Of the 268 and 266 patients included in the voclosporin and control arms of the pooled analysis, respectively, 217 and 215 patients had a baseline UPCR greater than 2 g/g (mean [SD], 5.1 [3.3] vs. 4.6 [2.8] g/g, respectively). At one year, the change from baseline in least squares mean UPCR was less than 3.8 (0.1) g/g in the voclosporin arm, compared to -3.1 (0.2) g/g in the control arm (difference vs. control, -0.7; p=0.0003).
A significantly greater percentage of voclosporin-treated patients achieved CRR at one year compared to the control arm (41.0% vs. 21.9%; odds ratio [OR] 2.48). Across biopsy classes, the highest rates of CRR were observed in Class III patients treated with voclosporin (50% vs. 16.1% in control, p=0.0126), followed by Class IV (44% vs. 23.8%, p=0.0019), Class V with III or IV lesions (37.7% vs. 17% p=0.0306), and Class V (31.3% vs. 28.6%, p=0.81).
CRR rates were numerically greater in subgroups of voclosporin-treated patients, including both sexes and across all ages, races, ethnicities, biopsy classes, and eGFR levels assessed, as indicated with OR >1
Similar rates of AEs were reported in both arms and mean eGFR levels were similar and stable over one year of treatment.
Related news and insights
Regeneron Pharmaceuticals, Inc. and Sanofi announced that the FDA has accepted for Priority Review the supplemental Biologics License Application (sBLA) for Dupixent (dupilumab) to treat children aged 1 to 11 years with eosinophilic esophagitis (EoE)
Sandoz, a global leader in generic and biosimilar medicines, announced that the European Commission (EC) granted marketing authorization for the first and only biosimilar Tyruko (natalizumab), developed by Polpharma Biologics. The authorization covers treatment as a single disease-modifying therapy (DMT) in adults with highly active RRMS, the same indication as approved by the EC for the reference medicine Tysabri (natalizumab)
Alzheon, Inc., announced statistically significant and clinically relevant reduction in plasma biomarkers of neurodegeneration, preservation of brain volume, and positive cognitive effects in Early AD patients who are carriers of apolipoprotein e4 allele (APOE4) following 24 months of treatment with investigational agent ALZ 801 in the Phase II biomarker trial