AURORA shines light on novel drug for lupus nephritis
The novel calcineurin inhibitor (CNI) voclosporin showed superiority over placebo on a background of standard-of-care (SOC) in patients with active lupus nephritis (LN), the AURORA* trial has shown.
“Voclosporin has four times the potency of cyclosporine A … The positive benefit-risk profile observed [in our study] confirms the treatment effect seen in AURA-LV** when comparing voclosporin … in combination with background SOC vs SOC alone,” said Dr Dawn Caster from the University of Louisville in Kentucky, US, who presented the findings at the ERA-EDTA 2020 virtual congress.
The study met its primary efficacy endpoint, with more patients on voclosporin achieving renal response*** at week 52 vs placebo (40.8 percent vs 22.5 percent; odds ratio [OR], 2.65; p<0.001). [ERA-EDTA 2020, abstract MO019]
All secondary endpoints were also met, to include renal response at week 24 (32 percent vs 20 percent; OR, 2.23; p=0.002) and partial renal responses at weeks 24 (70 percent vs 50 percent; OR, 2.43; p<0.001) and 52 (70 percent vs 52 percent; OR, 2.26; p<0.001). Time to renal response (hazard ratio [HR], 2.02) and time to 50-percent reduction in UPCR# (HR, 2.05; p<0.001 for both) were both faster with voclosporin vs placebo.
The eGFR## change from baseline to week 52 was –1.2 mL/min and was not statistically significant. Nonetheless, the levels were stable throughout the study. The fractions of patients with severe declines in eGFR (>30 percent) were similar in both voclosporin and placebo arms (10.1 percent vs 10.2 percent).
Adverse event (AE) rates were similar between the voclosporin and placebo arms (91 percent vs 89 percent), including serious AEs (21 percent for both). No deaths from treatment-related AEs were reported. “[T]he addition of voclosporin [to SOC] did not increase the risk of AEs including serious infection or death,” noted Caster.
“[Taken together, these findings suggest that] the odds of achieving renal response on voclosporin was 2.65 times greater than control, while maintaining a comparable safety profile,” said Caster.
A total of 357 individuals were randomized 1:1 to receive voclosporin 23.7 mg BID or placebo over background SOC (ie, mycophenate mofetil 2 g QD plus corticosteroids). Daily steroid dose was rapidly tapered from 20–25 mg at week 1 to 2.5 mg by week 16; at which point, 80 percent of participants in both arms had successfully dropped their dose to ≤2.5 mg. By week 52, ~75 percent of participants who completed the trial were receiving ≤2.5 mg of steroids.
Participants generally had well-preserved eGFR (mean, 91 mL/min/1.73 m2) with significant proteinuria (UPCR; mean, 4 mg/mg) at baseline. Each arm comprised a similar number of participants (86 percent in each arm) with proliferative lesions (ie, Class III/IV lesions +/- Class V).
Of note was the inclusion of participants who had pure Class V lesions (14 percent in each arm). “[AURORA] looked at Class V patients separately and had a high percentage of patients with mixed lesions. I think this is a great potential with [regard to] the podocyte-modulating capabilities of CNIs, [which protect against proteinuria],” said Caster.
“[It is reassuring] to have … positive results in LN after a very long time of not having anything … [I]n this very difficult-to-treat disease, hopefully, someday, we will have more precision medicine approach, and understand which patients are more T-cell– [or] B-cell–mediated,” she added.