Post hoc data boost voclosporin efficacy for severe lupus nephritis

In the post hoc analysis of the AURORA 1 and 2 trials, the novel calcineurin inhibitor voclosporin was effective in achieving complete renal response (CRR)* in individuals with severe lupus nephritis** (LN).

“The treatment benefit of voclosporin was observed in patients with severe disease across the 3-year treatment period,” said Dr Hanni Menn-Josephy from the Boston University School of Medicine, Boston, Massachusetts, US, during her presentation at ASN Kidney Week 2022.

More voclosporin-treated patients achieved CRR compared with those in the control arm at month 12 (47 percent vs 22 percent; odds ratio [OR], 4.41; p=0.008). These percentages improved by month 24 (57 percent vs 35 percent; OR, 3.08; p=0.022) and were sustained by month 36 (53 percent vs 35 percent; OR, 2.92; p=0.036). [ASN Kidney Week 2022, session FR-OR58]

Mean corrected estimated glomerular filtration rate (eGFR) and serum creatinine level were also stable throughout the study. These effects were sustained during the follow-up visit 4 weeks after treatment discontinuation.

Clinically meaningful results

In the phase III AURORA 1 study (n=179 [voclosporin] and 178 [control]), the addition of voclosporin (23.7 mg BID) to mycophenolate mofetil (MMF) and low-dose steroids led to significantly greater reductions in proteinuria and increased CRR rates in LN patients. The primary efficacy endpoint of CRR at month 12 was achieved in 41 percent of voclosporin recipients as opposed to 22 percent in the control arm (OR, 2.65; p<0.0001). [Lancet 2021;397:2070-2080]

“[These findings correlate with the] treatment goals for patients with LN, which include reducing proteinuria to preserve kidney function and to limit progression to end-stage kidney disease (ESKD),” said Menn-Josephy.

Patients who completed treatment in AURORA 1 were enrolled in AURORA 2, continuing the same dose of blinded therapy for 2 more years (n=116 [voclosporin] and 100 [control]). After 4 months of treatment, about 80 percent of patients were receiving <5 mg prednisone daily, which was maintained throughout AURORA 1 and 2 up until week 52.

The current 36-month analysis comprised patients from AURORA 2 who had severe LN (n=47 and 37 in the voclosporin and control arms, respectively). Mean eGFR was well-balanced between arms (79 vs 82 mL/min/1.73 m²), as was mean urine-protein creatinine ratio (UPCR; 1.1 vs 1.5 mg/mg).

There were comparable rates of adverse events (AEs) between the voclosporin and control arms (98 percent vs 97 percent), with infections being the most common type of AE. Two serious AEs (coronavirus infection) occurred in each arm. No deaths were reported in either arm.

“[Our findings showed that] patients with severe LN who were treated with voclosporin in combination with MMF and low-dose steroids achieved higher CRR rates … compared with patients receiving MMF and low-dose steroids only over a 3-year follow-up period,” said Menn-Josephy. The eGFR and serum creatinine remained stable over time, with similar safety outcomes in both arms.

LN may progress to irreversible renal tissue damage if poorly controlled. “[These findings are] clinically meaningful, given that patients with severe disease are at higher risk of worse long-term outcomes and ESKD development,” said Menn-Josephy.