Voclosporin Demonstrates Continued Long-Term Safety in Lupus Nephritis

Findings from the AURORA 2 study showed treatment with voclosporin (Lupkynis) was linked to long-term safety, with no increase in safety signals, in adult patients with lupus nephritis, according to research presented at the 2023 Congress of Clinical Rheumatology West.¹ The efficacy of the medication was maintained over a 3-year period, along with continued reductions in the urine protein creatine ratio (UPCR), and a greater proportion of patients were able to achieve a complete renal response (CCR) in the voclosporin group compared with controls.

Samir Parikh, MD

Credit: Ohio State University Wexner Medical Center

The drug, a novel calcineurin inhibitor, has recently been approved in the United States and Europe for the treatment of lupus nephritis. Previously, the phase 3 AURORA 1 study revealed adding voclosporin to mycophenolate mofetil (MMF) plus a regimen of low-dose oral steroids was able to significantly increase CCR rates at week 52.

AURORA 2 was a continuation study assessing voclosporin treatment compared to controls for 2 additional years following the completion of AURORA 1. Eligible patients were those who completed the first trial and opted to continue receiving the same dose of blinded therapy, in addition to MMF 2 g plus oral corticosteroids. The primary outcome was the long-term safety of the drug, as well as efficacy outcomes.

More than half (60.5%, n = 216) of the patients enrolled in the first trial (n = 357) opted to continue with the long-term extension study, of which 116 were placed in the voclosporin group and 100 received the placebo. The mean age was 35.4 years in the control cohort and 32.3 years in the voclosporin cohort. Most demographics were comparable across treatment arms, although the voclosporin group had a higher number of Black patients (18 vs 7, respectively).

More patients treated with voclosporin had a CCR at both month 12 (voclosporin: n = 61 [52.5%]; control: n = 34 [34.0%]; odds ratio [OR] 2.30; P - .004) and month 36 (voclosporin: n = 59 [50.9%]; control: n = 39 [39.0%]; OR 1.74; P = .05). Additionally, the mean reductions in UPCR obtained during AURORA 1 continued throughout AURORA 2 in both treatment groups.

Significantly more patients receiving voclosporin had a good renal outcome, defined by investigators as achieving adequate response (100 vs 73 patients, respectively) with no renal flare (77 vs 52 patients, respectively).

A small and early decrease in mean estimated glomerular filtration rate (eGFR) was observed in the voclosporin group in AURORA 1 within the first 4 weeks. However, eGFR then remained stable throughout both studies. An eGFR reduction >30% from baseline was experienced in 12.1% (n = 14/116) of patients receiving the study drug and 10% (n = 10/100) of controls.

No new adverse events (AEs) were reported in the voclosporin group, and the rates of AEs decreased over the study period. Most patients reported experiencing AEs categorized as mild or moderate in severity (voclosporin: 87.9%; placebo: 85.0%). AEs led to drug discontinuation in 9.5% of those receiving voclosporin and 17.0% of controls.

“AURORA 2 demonstrates a positive benefit-risk profile of voclosporin for the treatment of lupus nephritis in adults and provides further evidence to support the use of lower doses of steroids in the treatment of this disease,” wrote Samir Parikh, MD, clinical associate professor of internal medicine at the Ohio State University Wexner Medical Center, and colleagues.

References

1. ^{Parikh SV, Arriens C, Hodge L, Mela C, et al. Voclosporin for Lupus Nephritis: Assessment of Long-term Safety and Efficacy Including Renal Outcome over Three Years of Treatment in the Phase 3 AURORA 1 and AURORA 2 Studies. Congress of Clinical Rheumatology. September 2023.}