Background/Purpose: Voclosporin (VCS) is a novel calcineurin inhibitor (CNI) with a favorable metabolic profile and a consistent predictable dose response potentially eliminating the need for therapeutic drug monitoring.

Voclosporin has been evaluated for the treatment of lupus nephritis (LN) in two double blind RCTs, the Phase 2 AURA-LV and Phase 3 AURORA 1 trials representing the largest successful LN program to date.  Previously reported results from these studies demonstrated that the addition of VCS to MMF and low-dose steroids resulted in statistically superior renal response at 24 weeks and at one year (AURA-LV 48 weeks, AURORA 1 52 weeks).

Methods: The AURORA 1 and AURA-LV studies were of similar design and conducted in comparable patient populations. The results of the efficacy and safety analyses from AURORA 1 were consistent with and confirmed the conclusions from the AURA-LV study. The data from both studies for subjects treated with the recommended VCS dose of 23.7 mg BID(AURORA 1; n=179, AURA-LV; n=89) or with matching placebo (AURORA 1; n= 178, AURA-LV; n=88) were therefore pooled for an integrated analysis of efficacy.

The primary endpoint in both studies was renal response (RR), defined as UPCR of ≤ 0.5 mg/mg, eGFR ≥ 60 mL/min, or no confirmed decrease from baseline in eGFR of > 20%, < 10 mg/d prednisone for at least 8 weeks prior to endpoint assessmentand no administration of rescue medication.

Results: In the integrated analysis, treatment with VCS resulted in a clinically meaningful and statistically significant higher renal response (RR) rate (43.7%) compared to placebo (23.3%) at 1 year (OR 2.76, 95% CI: 1.88, 4.05; p < 0.0001) and at 6 months (VCS 31.7%; placebo 20.3%), [OR: 2.01; 95% CI: 1.34, 3.01; p=0.0008].  

Furthermore, a 50% reduction in UPCR from baseline at any time was achieved by 93.7% of subjects treated with VCS compared with 75.2% of subjects receiving placebo, with a median time to 50% reduction in UPCR of 29 days versus 58 days, respectively. The time taken to reach a 50% reduction in UPCR was significantly shorter for the voclosporin group than the placebo group (HR 1.96; 95% CI: 1.61, 2.38; p< 0.0001).  At one year 160 (75.8%) patients in the VCS arm and 150 (73.9%) patients in the placebo arm were on oral prednisone ≤ 2.5 mg/d.

Conclusion: Integrated efficacy analysis further supports efficacy results from the AURORA 1 and AURA-LV trials.  Adult patients with LN treated with VCS on top of MMF and steroids achieve meaningful reductions in proteinuria and achieve that reduction faster compared to patients on MMF and steroids alone.    

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/integrated-efficacy-of-the-aurora-1-and-aura-lv-trials-confirms-voclosporin-rapid-proteinurea-reduction-in-the-presence-of-low-dose-steroids/