Voclosporin, a novel calcineurin inhibitor, is effective in patients with severe lupus nephritis, and it is well tolerated in all patients for up to 3 years, according to 2 teams of investigators reporting at the American Society of Nephrology’s Kidney Week 2022 conference.
In a post hoc analysis of the AURORA trials, 47 patients receiving voclosporin and 37 patients receiving placebo had severe class 3 or 4 (with or without class 5) lupus nephritis with active lesions and urine protein creatinine ratio (UPCR) of 3 mg/mg or more. At baseline, the mean UPCR was 6.02 mg/mg in the voclosporin arm and 6.08 mg/mg in the control arm. All patients received background treatment with mycophenolate mofetil (MMF) and low-dose steroids.
Complete renal response (defined as a UPCR of 0.5 mg/mg or less with stable renal function, use of low-dose steroids, and no use of rescue medication) occurred in a higher proportion of the voclosporin than control arm at 1 year (46.8% vs 21.6%), 2 years (57.4% vs 35.1%), and 3 years (53.2% vs 35.1%). The voclosporin arm had significant 4.4-, 3.1-, and 2.9-fold increased odds of complete renal response at years 1, 2, and 3, respectively, Hanni Menn-Josephy, MD, of the Boston University School of Medicine in Massachusetts, reported in a poster presentation.
The rates of serious adverse events were similar in the voclosporin (21.3%) and control (27.0%) arms, with 1 death in the control arm, he reported.
“This is clinically meaningful given that patients with severe disease are at higher risk of worse long-term outcomes and development of end stage kidney disease,” Dr Menn-Josephy stated.
In a separate poster on the AURORA 2 trial, Samir V. Parikh, MD, of The Ohio State University Wexner Medical Center in Columbus, reported that continued use of voclosporin for 3 years in patients with proliferative lupus nephritis maintains efficacy with no increase in safety signals.
Among completers of the AURORA 2 trial, more patients taking voclosporin than placebo had a complete renal response at 12 months (52.6% vs 34.0%) and 36 months (50.9% vs 39.0%). Mean reductions in UPCR at 12 months were maintained up to 36 months.
In addition, significantly more patients in the voclosporin than placebo arm had a good renal outcome, defined as adequate response (sustained reduction in UPCR to 0.7 mg/mg or less) with no renal flare: 66.4% vs 54.0%.
After an initial dip in estimated glomerular filtration rate (eGFR) at 4 weeks in the voclosporin arm, eGFR remained stable. Reduction in eGFR of more than 30% occurred in similar proportions of the voclosporin and placebo arms (12.1% vs 10.0%). Mean blood pressure was stable in both arms over time. Mean serum potassium and magnesium levels remained within normal range.
Mild to moderate adverse events occurred in 87.9% vs 85.0% of the voclosporin and placebo groups, respectively. Serious adverse events affected a greater proportion of the placebo than voclosporin arm. Drug discontinuation due to adverse events occurred in 9.5% of the voclosporin arm and 17.0% of the placebo arm.
“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,” Dr Parikh’s team concluded.
Disclosure: This research was supported by Aurinia Pharmaceuticals. Please see the original references for a full list of disclosures.
Menn-Josephy H, Truman M, Palmen M, Leher H. Efficacy and safety of voclosporin over 3 years in patients with severe lupus nephritis. Presented at: Kidney Week 2022; November 3-6, Orlando, Florida. Abstract FR-OR58.
Parikh SV, Arriens C, Hodge LS, Mela C, Leher H. Voclosporin for Lupus Nephritis: Assessment of Long-Term Safety and Efficacy Including Renal Outcome Over 3 Years of Treatment in the Phase 3 AURORA 1 and AURORA 2 Studies. Presented at: Kidney Week 2022; November 3-6, Orlando, Florida. Poster TH-PO486.