Background:Voclosporin, a novel calcineurin inhibitor (CNI), has been tested successfully in two pivotal trials in adult patients with lupus nephritis.Previously reported results from the Phase 3 AURORA 1 study and the Phase 2 AURA-LV study showed that compared with mycophenolate mofetil (MMF) and low-dose steroids alone, the addition of voclosporin significantly increased the renal response rate and reduced proteinuria, as measured by urine protein creatinine ratio (UPCR), in patients with lupus nephritis (LN) at approximately one year of treatment (48 weeks in AURA-LV and 52 weeks in AURORA 1).Objectives:Patients that completed one year of treatment in the AURORA 1 study were eligible to enroll into the two-year, blinded, controlled extension study, AURORA 2. Here we report the first interim analysis of the ongoing AURORA 2 study.Methods:Patients completing AURORA 1 were eligible to continue the same randomized treatment of voclosporin (23.7 mg BID) or placebo, in combination with MMF (1 g BID) and low-dose oral steroids in the AURORA 2 extension. This interim analysis evaluated UPCR and estimated glomerular filtration rate (eGFR) in patients with up to two years of total treatment: one year from AURORA 1 and up to one year in AURORA 2.Results:116 patients in the voclosporin arm and 100 patients in the control arm enrolled in the extension study, of which 73 patients in the voclosporin arm and 51 patients in the control arm had received two years of treatment at the time of this interim analysis. Mean UPCR at pre-treatment (AURORA 1) baseline was 3.94 mg/mg in the voclosporin arm (n=116) and 3.87 mg/mg in the control arm (n=100). The LS mean change in UPCR from pre-treatment baseline to year two was -3.1 mg/mg for the voclosporin arm (n=73) and -2.1 mg/mg for control arm (n=51; Table 1). Mean eGFR at pre-treatment (AURORA 1) baseline was 79.6 mL/min for the voclosporin arm (n=116) and 78.9 mL/min for the control arm (n=100) and at year two, was 79.0 mL/min for the voclosporin arm (n=73) and 82.9 mL/min for the control arm (n=51). There was a small early decrease in mean eGFR in the first four weeks of treatment (in AURORA 1) after which eGFR remained stable throughout year one and year two. Additionally, there were no unexpected new AEs observed in patients who continued with voclosporin treatment compared to control-treated patients for more than one year.Table 1.UPCRControl (n=100)Voclosporin (n=116)Treatment Comparison of Voclosporin to ControlnUPCR (mg/mg)nUPCR (mg/mg)UPCR (mg/mg)p-valuePre-treatment baseline, mean1003.871163.94NCNCChange from pre-treatment baseline, LS mean Year 1100-2.4116-3.0-0.60.0080 Year 251-2.173-3.1-1.00.0004LS, least squares; NC, not calculated; UPCR, urine protein creatinine ratio.Mixed effects model for repeated measures (MMRM) analysis of LS mean change from pre-treatment baseline for UPCR included terms for baseline covariate, treatment, visit and treatment by visit interaction. Integrated results include data from pre-treatment baseline of AURORA 1, the one-year treatment period in AURORA 1 and up to a one-year treatment period in AURORA 2.Conclusion:Patients in the voclosporin treatment arm maintained meaningful reductions in proteinuria with no change in mean eGFR at two years of treatment. Additional AURORA 2 efficacy and safety data will be provided at the conclusion of the study.Disclosure of Interests:Amit Saxena: None declared, Paola Mina-Osorio Shareholder of: Aurinia Pharmaceuticals Inc., Employee of: Aurinia Pharmaceuticals Inc., Christopher Mela Shareholder of: Aurinia Pharmaceuticals Inc., Employee of: Aurinia Pharmaceuticals Inc., Vanessa Berardi Shareholder of: Aurinia Pharmaceuticals Inc., Employee of: Aurinia Pharmaceuticals Inc.
POS-324 Ultra-low dose Rituximab regimen for the treatment of lupus nephritis: A preliminary observational study