Voclosporin is effective in achieving complete renal response in severe lupus nephritis

Background: Voclosporin is a novel calcineurin inhibitor with a favorable metabolic profile and a consistent dose-concentration relationship. The Phase 3 AURORA 1 trial demonstrated that compared to mycophenolate mofetil (MMF) and low-dose steroids, adding voclosporin significantly increased complete renal response (CRR) rates in patients with lupus nephritis (LN). We report the results of a post-hoc analysis evaluating if the efficacy of voclosporin in patients with severe LN is similar to the overall population of AURORA 1. Methods: Patients with systemic lupus erythematosus, biopsy-proven active LN (Class III, IV or V ± III/IV), and proteinuria of ≥1.5 mg/mg (≥2 mg/mg for Class V) were eligible to enroll in AURORA 1. Overall, 179 and 178 patients were randomized to the voclosporin (23.7 mg BID) and control arms, respectively. All patients received MMF (1 g BID) and low-dose oral steroids. Severe LN was defined as baseline UPCR ≥3 mg/mg with Class III or IV biopsy (± Class V) with active lesions. Renal function and serology were evaluated to ensure the population was representative of severe disease in clinical practice. CRR was defined as UPCR ≤0.5 mg/mg with stable renal function, use of lowdose steroids and no use of rescue medication. Results: There were 76 and 72 patients in the voclosporin and control arms, respectively, with severe disease. Mean (SD) UPCR at baseline was 5.9 (2.4) mg/mg (Table 1). CRR at one year was 34.2% and 11.1% in the voclosporin and control arms, respectively (odds ratio 4.43, p=0.001; Figure 1). Conclusions: In patients with severe LN, adding voclosporin to MMF and steroids results in statistically significantly higher CRR rates. This is clinically meaningful given that patients with severe disease are at higher risk of worse long-term outcomes and development of ESKD.