#3032 EFFICACY AND SAFETY OF VOCLOSPORIN IN PATIENTS WITH PROTEINURIA ≥2 MG/MG: AN INTEGRATED ANALYSIS OF THE AURA-LV AND AURORA 1 STUDIES

Abstract

Abstract Background and Aims Proteinuria has been established as a mediator of progressive renal damage in many nephropathies. However, recent studies of several monoclonal antibodies demonstrated a lack of efficacy in patients with lupus nephritis and moderate to high levels of proteinuria (UPCR ≥2 to ≥3 mg/mg), potentially due to an increase in renal antibody clearance.1-4 Given that, we examined the efficacy and safety of voclosporin in patients with lupus nephritis and a UPCR of ≥2 mg/mg using the pooled dataset from the Phase 2 AURA-LV and Phase 3 AURORA 1 trials. Method Both studies enrolled patients with biopsy-proven LN (Class III, IV, or V ± III/IV, biopsied within 6 months in AURA-LV or up to 2 years in AURORA 1) and proteinuria ≥1.5 mg/mg (≥2 mg/mg for Class V). Patients were randomized to receive either voclosporin (23.7 mg BID) or placebo and treated for up to one year (48 weeks [AURA-LV], 52 weeks [AURORA 1]); all patients received MMF and low-dose steroids. For this post-hoc analysis, changes in UPCR and renal response rates were evaluated in patients with baseline UPCR ≥2 mg/mg. Complete renal response (CRR) was defined as UPCR ≤0.5 mg/mg with stable renal function, low-dose steroids, and no rescue medication; partial renal response (PRR) was defined as a ≥50% reduction in UPCR from baseline. Safety outcomes were also assessed. Results The pooled analysis included 268 and 266 patients in the voclosporin and control arms, respectively. Of those, 217 and 215 patients had UPCR ≥2 mg/mg (baseline mean [SD], 5.2 [3.4] vs. 4.6 [2.9] mg/mg, respectively). A significantly greater percentage of voclosporin-treated patients achieved a CRR at one year compared to the control arm (41.0% vs. 21.9%; odds ratio [OR] 2.48, p<0.0001, Figure 1A). Similarly, significantly more patients in the voclosporin arm (69.6%) than control arm (50.0%) achieved a PRR at the same time point (OR 2.3, p<0.0001); this endpoint was met significantly earlier in voclosporin-treated patients as well (29 vs. 57 days, hazard ratio [HR] 2.0, p<0.0001). The median time to UPCR ≤0.5 mg/mg was also significantly earlier in the voclosporin arm (211 days); less than 50% of the control arm achieved this endpoint within the study period (OR 1.9, p<0.0001, Figure 1B). Adverse event rates were comparable in both arms (Table 1), and mean eGFR levels were similar and stable over the study period, a trend that was maintained for AURORA 1 patients who continued randomized treatment for another two years in the AURORA 2 study. Conclusion Consistent with results from the overall pooled study population, patients with UPCR ≥2 mg/mg at baseline treated with voclosporin achieved significantly higher renal response rates and significantly earlier reductions in UPCR than patients treated with MMF and low-dose steroids alone. These findings are clinically important given the lack of effective therapies available for patients with high baseline proteinuria.