Phase 3 Data Provide Evidence of Voclosporin as Long-Term Treatment for Lupus Nephritis

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A significantly higher number of patients receiving voclosporin achieved good renal outcome when compared with placebo.

According to phase 3 data presented at the 2022 American Society of Nephrology (ASN) Annual Meeting, voclosporin was able to maintain significant reductions in proteinuria for 3 years in patients with lupus nephritis, indicating the drug’s benefit as a long-term treatment.

Samir V. Parikh, MD, The Ohio State University Wexner Medical Center, and investigators assessed voclosporin’s safety and efficacy for the treatment of lupus nephritis in the AURORA 1 and AURORA 2 trials. They also evaluated renal outcome over the cumulative 3 year study period.

In AURORA 1, voclosporin was combined with mycophenolate mofetil (MMF) and low-dose steroids and given to patients with lupus nephritis. After a year of treatment, they observed significant reductions in proteinuria in patients on the treatment regimen.

For the next 2 years, this investigation continued as AURORA 2 and patients on the intervention were compared with a placebo group.

All participating patients received MMF and low-dose steroids and depending on which group they were randomized to, also received voclosporin or placebo. Both studies assessed the same outcomes: adverse events (AEs), eGFR, urine protein-creatinine ratio (UPCR), good renal outcome, and renal flare.

Patients who achieved an adequate response (i.e. sustained reduction in UPCR to ≤0.7 mg/mg) and didn’t experience renal flare (i.e. an increase to UPCR >1 mg/mg from a post-response UPCR of <0.2 mg/mg or an increase to UPCR >2 mg/mg from a post-response UPCR of 0.2 to 1.0 mg/mg) were considered to have a good renal outcome.

Not only were the reductions in UPCR maintained throughout the final 2 years, but 66.4% of patients in the intervention group achieved a good renal outcome compared with 54% in the placebo group. Therefore, the effect of voclosporin was clinically significant.

Renal flare with adequate response occurred in 24 of 101 (23.8%) patients taking voclosporin and 19 of 73 (26%) patients in the control group. Investigators noted that 69.8% of all patients with renal flares completed study treatment.

The overall rates of serious adverse events were similar, with 26.7% of those taking voclosporin, and 28% of those taking placebo experiencing at least one. No deaths were reported in the intervention group and 4 deaths were reported in the control group (pulmonary embolism, n=1; coronavirus infection, n=3). The mean eGFR was stable and within normal range for the duration of the study.

“Voclosporin was well-tolerated over 3 years of treatment,” investigators concluded. “The significant reductions in proteinuria initially achieved in AURORA 1 were maintained throughout AURORA 2 and more patients in the voclosporin arm achieved a good renal outcome. These data provide evidence of a long-term treatment benefit of voclosporin in patients with lupus nephritis.”