Background/Purpose:

Voclosporin (VCS) is a novel CNI with a favorable metabolic profile, no observed effect on electrolytes, and a predictable dose response potentially eliminating the need for therapeutic drug monitoring.

VCS has completed testing in a global phase II trial, AURA, in patients with active lupus nephritis (LN).  In AURA, two doses of VCS (23.7mg BID, 39.5mg BID) were evaluated vs placebo in a double blind RCT when added on top of MMF (2g/ day) and a stringent steroid taper.

Methods:

The primary endpoint was 24-week complete remission (CR). However, blinding and randomization were maintained through 48 weeks permitting further efficacy assessments at 48 weeks.  CR required a confirmed UPCR of <0.5 mg/mg, eGFR >60 ml/min without a decrease of >20% from baseline, low-dose steroids for at least 8 weeks prior to the endpoint assessment and no administration of rescue medications.

Results:

Previously reported 24-week data showed a statistically significant CR improvement in patients receiving low dose VCS vs control (32.6% vs. 19.3%; OR: 2.03, p=0.045) and 27.3% in high dose VCS (p=NS). Furthermore, at 24 weeks both doses of VCS demonstrated statistical superiority over control in partial response (PR, 50% reduction in proteinuria from baseline) time to CR and time to PR.  VCS treatment effect increased at 48 weeks with 49.4% low-dose (OR 3.21, p<.001) and 39.8 % high dose (OR 2.1, p= .026) VCS patients achieving CR vs 29.6% of control patients.   Additionally, all low dose VCS patients in CR at 24 weeks remained in CR at 48 weeks. More AEs (84% control, 96% high, 91% low) and SAEs (19% control, 25% high, 28% low) were observed in both VCS arms compared to control. There were 13 deaths (low dose 10, high dose 2, control 1).  All deaths were considered unrelated to VCS treatment by investigators and were consistent with cause seen in other LN studies.  Eleven of thirteen deaths were clustered in sites with compromised access to standard of care and which disproportionately recruited to the low dose VCS arm. Following completion of study treatment, 3 control arm patients died while one developed a malignancy.  No additional deaths were reported in the low dose VCS arm following 24 weeks.

We now present a 48-week CR subgroup analysis based on ethnicity, sex and age.

Table 1: 48-week complete remission ethnic, sex and age subgroups

Conclusion:

48-week subgroup analysis demonstrates sustained VCS treatment effect that was consistent across subgroups.  AURA was not powered to show statistical significance in these subgroups; however, odds ratios strongly favored low and high dose VCS across these 8 subgroups. Further data regarding VCS treatment effect in subgroups of patients with active LN will is currently being generated in the phase III AURORA trial.