Pooled analysis reinforce voclosporin potential for lupus nephritis

In a pooled, post hoc analysis of the AURA-LV and AURORA 1 studies, lupus nephritis (LN) patients with moderate-to-high baseline levels of proteinuria (UPCR* ≥2 to ≥3 mg/mg) who were receiving add-on voclosporin achieved higher renal response rates and earlier UPCR reductions vs those who were only treated with the control regimen.

CRR** rates were significantly higher in the voclosporin vs the control arm at 6 months (29 percent vs 19 percent; odds ratio [OR], 1.79; p=0.0116) and 1 year (41 percent vs 22 percent; OR, 2.48; p<0.0001).

“The 1-year results were consistent with those seen in the overall pooled study population,” said Dr Salem Almaani from The Ohio State University, Columbus, Ohio, US, at ERA 2023. Overall, CRR at 1 year was 44 percent with voclosporin and 23 percent with control (OR, 2.76; p<0.0001).

A similar trend favouring voclosporin over control was seen in terms of PRR*** at both timepoints (72 percent vs 53 percent; OR, 2.25 [6 months] and 70 percent vs 50 percent; OR, 2.30 [1 year]; p<0.0001 for both).

Change from baseline UPCR was greater in the voclosporin vs the control arm at 1 year (least squares mean, –3.8 vs –3.1 mg/mg; p=0.0003).

Voclosporin was also associated with earlier reductions in proteinuria from baseline (time to >50-percent reduction in UPCR, 29 vs 57 days; hazard ratio [HR], 1.88; p<0.0001). “Early reductions in proteinuria are predictive of improved long-term outcomes,” said Almaani.

Median time to UPCR ≤0.5 mg/mg was 211 days with voclosporin, whereas with the control regimen, it was not determinable, as only <50 percent of patients achieved this endpoint within the trial period (HR, 1.9; p<0.0001).

“After an early and expected decrease in eGFR^# at week 4 in the voclosporin arm, mean corrected eGFR was stable over 1 year of treatment in both arms,” added Almaani. According to the investigators, this trend was maintained for AURORA 1 participants who continued treatment for 2 more years in AURORA 2.

Safety profiles were comparable in both voclosporin and control arms, as reflected by the similar rates of adverse events (AEs; 92 percent vs 88 percent), serious AEs (23 percent vs 20 percent), treatment-related serious AEs (4 percent vs 3 percent), and drug discontinuation due to AEs (14 percent for both).

There were six deaths in the voclosporin arm vs three in the control arm, but no treatment-related AEs led to death.

Effective treatments lacking

LN is a serious SLE^## manifestation than can lead to permanent, irreversible kidney damage if poorly controlled. [ir.auriniapharma.com/press-releases/detail/297/aurinia-showcases-three-oral-presentations-for-lupkynis, accessed July 23, 2023]

Furthermore, proteinuria has been established as a mediator of progressive renal damage in several nephropathies, and evidence shows limited efficacy of monoclonal antibody treatments in LN patients with moderate-to-high proteinuria. [Ann Rheum Dis 2022;81:100-107; Ann Rheum Dis 2022;81:496-506; Lupus 2022;31:424-432; Kidney Int 2022;101:403-413]

The investigators pooled data from two 1-year double-blind trials on voclosporin, a novel calcineurin inhibitor approved for the treatment of active LN, which had similar designs and outcomes. [Lancet 2021;397:2070-2080; Kidney Int 2019;95:219-231]

The pooled dataset included 534 participants. Of these, 432 had UPCR ≥2 mg/mg (mean, 5.1 and 4.6 mg/mg for voclosporin and control, respectively). A total of 217 patients were given voclosporin 23.7 mg BID on top of a control regimen comprising mycophenolate mofetil and low-dose glucocorticoids (mean age 31.9 years); 215 patients were on the control regimen alone (mean age 33.2 years). About 90 percent of participants were female.

“[Overall, the efficacy of voclosporin] was observed regardless of baseline demographics or clinical characteristics,” said Almaani. “These findings are clinically important given the lack of effective therapies available for patients with high baseline proteinuria.”

“[The results] support the use of voclosporin in LN patients with moderate-to-high proteinuria,” Almaani concluded.