Background Voclosporin (VCS) is a novel CNI intended for use in the treatment of autoimmune diseases such as lupus nephritis (LN). VCS's unique structure allows for less pharmacokinetic-pharmacodynamic variability and a potentially improved safety profile compared to other CNIs.
Objectives Achievement of complete remission (CR) as assessed at week 24 (primary objective) and assessment of the efficacy over 48 weeks (secondary objective), with 2 doses of VCS (low dose VCS: 23.7mg BID and high dose VCS: 39.5mg BID) vs. placebo in subjects with active LN.
Methods The double blind placebo controlled AURA study enrolled 265 subjects with active LN in 20 countries. Patients were randomized into 3 arms (placebo, low dose VCS or high dose VCS) in addition to MMF 2g/day and steroids (with rapid tapering). CR was defined as a confirmed urine protein/creatinine ratio (UPCR) of ≤0.5 mg/mg using first morning void and confirmed estimated glomerular filtration rate (eGFR, CKD-EPI equation) ≥60 mL/min/1.73 m2 or no decrease from baseline in eGFR of ≥20% in the presence of low dose steroids. Partial remission (PR) was defined as a 50% reduction in UPCR. UPCR assessments were made at each visit, together with biomarker data at regular intervals.
Results We now present the 48 week data showing improved CR rates over the 24 week data. The rate of CR was significantly higher in the low dose VCS compared to the control group (32.6% vs. 19.3%; OR: 2.03, p=0.045) at 24 weeks. It was 27.3% in the high dose VCS group (p=NS). Both doses of voclosporin demonstrated superiority to control using time to CR, PR (50% reduction in proteinuria) and time to PR.
At 48 weeks, 23.9% of patients on the control arm achieved CR comparted to 49.4% low dose (OR: 3.21, p<0.001) and 39.8% high dose (OR: 2.10, p<0.026). Over 92% of subjects experienced at least one adverse event (AE) with the most common two being infections (58% low, 66% high and 55% placebo) and GI disorders (43% low, 52% high and 38% placebo). The overall rate of serious adverse events (SAEs) was numerically higher in both voclosporin groups (28% low, 25% high, 19% placebo) with the nature of SAEs consistent with those observed in patients with highly active LN. Most deaths occurred in the first 2 months and were: low dose (infection3, ARDS2, thrombotic3, cardiac tamponade, pulmonary hemorrhage), high dose (infection, PE) and control (CVA). All were considered unrelated to drug exposure by the investigators. 3 additional deaths occurred in placebo patients after the conclusion of the 48 weeks of treatment.
Conclusions The AURA-LV study is the first global study demonstrating the beneficial effect of VCS, in combination with MMF and steroids, in the treatment of LN. Remission rate was rapid. VCS treatment resulted in increasing CR and PR seen by week 6 despite rigorous steroid taper (mean steroid dose 4 mg at week 16). Adverse events were higher in the treated patient group with the nature in keeping with immunosuppression. These promising data will be used to plan subsequent studies of voclosporin in LN.
Acknowledgements This data was submitted on behalf of the AURA-LV study investigators.
Disclosure of Interest V. Dobronravov Grant/research support from: Aurinia Pharmaceuticals Inc., M. A. Dooley Grant/research support from: Aurinia Pharmaceuticals Inc., S. A. Haq Grant/research support from: Aurinia Pharmaceuticals Inc., I. Adzerikho Grant/research support from: Aurinia Pharmaceuticals Inc., O. Bugrova Grant/research support from: Aurinia Pharmaceuticals Inc., D. Isenberg: None declared, F. Houssiau: None declared, N. Solomons Shareholder of: Aurinia Pharmaceuticals Inc., Employee of: Aurinia Pharmaceuticals Inc., R. Huizinga Shareholder of: Aurinia Pharmaceuticals Inc., Employee of: Aurinia Pharmaceuticals Inc.