FC056: Early Reductions in Proteinuria with Voclosporin Treatment Across Lupus Nephritis Biopsy Classes: Pooled Data from the AURA-LV AND AURORA 1 Trials

Abstract

Abstract BACKGROUND AND AIMS Voclosporin, a novel calcineurin inhibitor, was approved by the FDA for the treatment of adults with active lupus nephritis (LN) in combination with background immunotherapy, and was successfully tested in two pivotal trials, AURA-LV (Phase 2) and AURORA 1 (Phase 3). Pooled data from these trials showed that the addition of voclosporin to mycophenolate mofetil (MMF) and low-dose steroids resulted in significantly higher complete renal response (CRR) rates at 24 weeks and 1 year of treatment in patients with LN. More patients in the voclosporin group achieved urine protein creatinine ratio (UPCR) reductions of ≥ 50% from baseline, and the median time to this endpoint was significantly shorter in the voclosporin group compared with the control group. Reduced proteinuria at 1 year is the best predictor of improved long-term renal outcomes in LN.[1,2] The current report evaluates the impact of voclosporin on the time to proteinuria reduction by biopsy class in pooled data from the AURA-LV and AURORA 1 trials. METHOD Both trials 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 mg/mg (≥2 mg/mg for Class V). The pooled analysis included 268 patients in the voclosporin (23.7 mg BID) group and 266 patients in the control group. All patients received MMF (target 1 g BID) and low-dose steroids (target dose 2.5 mg/day by week 16 according to protocol-defined steroid taper). For this post-hoc analysis, hazard ratios (HR) for the times to UPCR ≤ 0.5 mg/mg and UPCR reduction ≥ 50% from baseline were analyzed by biopsy class. RESULTS The addition of voclosporin resulted in faster times to both UPCR ≤ 0.5 mg/mg and UPCR reduction ≥ 50% from baseline in the overall study population and across individual biopsy classes (HR > 1; Table 1). Median times to UPCR of ≤ 0.5 mg/mg and UPCR reduction ≥ 50% from baseline for both pure Class III and pure Class IV were significantly shorter for patients treated with voclosporin than the respective control groups: 142 versus 372 days (Class III) and 142 versus ND (not determinable) days (Class IV) for UPCR ≤ 0.5 mg/mg; 25 versus 84 days (Class III) and 29 versus 57 days (Class IV) for UPCR reduction ≥ 50% from baseline. The differences between the voclosporin and control groups for pure Class III and pure Class IV were apparent within the first month of treatment and sustained at 1 year. Similar results were seen with mixed Class III/V and IV/V. Patients with pure Class V took the longest to achieve both UPCR endpoints; the difference between groups was not statistically significant. CONCLUSION Patients treated with voclosporin in addition to MMF and low-dose steroids achieved earlier reductions in proteinuria across all biopsy classes. As expected, patients with Class V disease took longer to reach both UPCR endpoints than patients with proliferative disease, suggesting this population of patients may require a longer duration of treatment. This analysis further supports the efficacy results observed in the individual AURA-LV and AURORA 1 trials, indicating faster time to response when voclosporin is added to standard of care agents MMF and steroids.