VOCLOSPORIN for LUPUS NEPHRITIS: RESULTS of the TWO-YEAR AURORA 2 CONTINUATION STUDY

ABSTRACT

Background: Voclosporin (VCS), a novel calcineurin inhibitor, was approved in the US in January 2021 for the treatment of adult patients with active lupus nephritis (LN) in combination with background immunosuppressive therapy. The Phase 3 AURORA 1 study showed that the addition of VCS to mycophenolate mofetil (MMF) and low-dose steroids in patients with LN signifcantly increased rates of complete renal response at 52 weeks. Objectives: Here we report the results of the completed continuation study, AURORA 2, which assessed the long-term safety and tolerability of VCS compared to placebo in patients with LN receiving treatment for an additional 24 months following completion of the AURORA 1 study Methods: Key inclusion criteria for the parent AURORA 1 study included a diagnosis of biopsy-proven active LN (Class III, I V, or V ± III/IV), proteinuria ≥1.5 mg/mg (≥2 mg/mg for Class V) and estimated glomerular fltration rate (eGFR) >45 mL/min/1.73 m2. Patients who completed AURORA 1 and who elected and were eligible to enter AURORA 2 continued on the same blinded therapy as at the end of AURORA 1 (either VCS or placebo twice daily in combination with MMF and low-dose steroids). Safety and tolerability were monitored, and eGFR, serum creatinine (SCr), and urine protein creatinine ratio (UPCR) were also assessed. Results: In total, 116 and 100 patients in the VCS and control arms enrolled in AURORA 2, with 92 (79.3%) and 73 (73.0%) patients in each respective arm receiving treatment to the end of AURORA 2. There were no unexpected safety signals in the VCS arm compared to control, with similar rates of serious adverse events reported in both arms (VCS [18.1%] vs. control [23.0%];Table 1). Eight patients in each arm experienced serious adverse events of infection;serious coronavirus infections were observed in 2 patients in the voclosporin arm and 5 patients in the control arm. There were 4 and 2 adverse events by preferred term of renal impairment reported in the VCS and control arms, respectively, none of which were considered serious, and no reports of acute kidney injury by preferred term in either arm. There were no deaths in the VCS arm during AURORA 2;four deaths were reported in the control arm (pulmonary embolism [n=1], coronavirus infection [n=3]). Mean eGFR and SCr levels remained stable through the end of AURORA 2. The difference between the VCS and control arms in LS mean change from baseline in eGFR was 2.7 mL/min/1.73 m2 at 4 weeks following study drug discontinuation (Figure 1). The mean reductions in UPCR observed in patients treated with VCS in AURORA 1 were maintained in AURORA 2 with no increase in UPCR noted at the follow-up visit 4 weeks after study drug discontinuation. Conclusion: Voclosporin was well-tolerated over 3 years of treatment with no unexpected safety signals detected. Further, eGFR remained stable throughout the study period, and the signifcant and meaningful reductions in proteinuria achieved in AURORA 1 were maintained. These data provide evidence of a longterm treatment beneft of VCS in patients with LN. Includes adverse events starting on or after the frst dose of study drug in AURORA 2 up to 30 days after the last dose and all events of death reported during study follow-up. Adverse events were aggregated by System Organ Class and Preferred Term and coded using Medical Dictionary for Regulatory Activities (MedDRA) Version 20.0. AE, adverse event.