Background Voclosporin, a novel calcineurin inhibitor, has been tested successfully in two pivotal trials in adult patients with lupus nephritis. 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 complete renal response rate at approximately one year of treatment. Patients that completed the AURORA 1 study were eligible to enroll in the AURORA 2 extension study. Here we report the first interim analysis of AURORA 2.
Methods AURORA 2 is a two-year, blinded, controlled extension study. Patients completing AURORA 1 continued the same randomized treatment in AURORA 2 of voclosporin (23.7 mg twice daily) or placebo, in combination with MMF (1 g twice daily) and low-dose steroids. The interim analysis evaluated urine protein creatinine ratio (UPCR) and estimated glomerular filtration rate (eGFR) in patients with up to two years of total treatment. In total, 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 received two years of treatment at the time of this interim analysis.
Results Mean UPCR at pre-treatment AURORA 1 baseline was 3.9 mg/mg in the voclosporin arm (n=116) and 3.9 mg/mg in the control arm (n=100). The least square (LS) mean change in UPCR from pre-treatment AURORA 1 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; figure 1). Mean corrected eGFR at pre-treatment AURORA 1 baseline was 79.6 mL/min/1.73 m2 for the voclosporin arm (n=116) and 78.9 mL/min/1.73 m2 for the control arm (n=100) and at year two, was 79.0 mL/min/1.73 m2 for the voclosporin arm (n=73) and 82.9 mL/min/1.73 m2 for the control arm (n=51). There was a small, expected, and early decrease in mean eGFR in the voclosporin arm 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 adverse events observed in patients who continued with voclosporin treatment compared to control-treated patients.
Mixed effects model for repeated measures (MMRM) analysis of least squares mean change from pre-treatment AURORA 1 baseline for UPCR included terms for baseline covariate, treatment, visit and treatment by visit interaction. Interim analysis of AURORA 2 patients includes data from pre-treatment baseline of AURORA 1, the one-year treatment period in AURORA 1 and up to one-year treatment period in AURORA 2.
Conclusions 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.
Acknowledgments Study funded by Aurinia Pharmaceuticals Inc.
Trial RegistrationClinicalTrials gov identifier: NCT03597464
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