Phase 3 Trial Offers Compelling Evidence for Voclosporin Supplementation Among Patients With Lupus Nephritis

Voclosporin has been shown to promote rapid renal response with long-term safety and tolerability for the treatment of patients with lupus nephritis (LN), according to study results published in Arthritis and Rheumatology.

Investigators assessed the long-term safety and tolerability of the novel calcineurin inhibitor voclosporin for the treatment of patients with LN, compared with placebo.

The multicenter, phase 3, double-blinded AURORA 2 study (ClinicalTrials.gov Identifier:  NCT03597464) was conducted, including a cohort of patients that completed 12 months of treatment with voclosporin in the AURORA 1 parent study.

Patients enrolled in the AURORA 2 trial received an additional 24 months of treatment with voclosporin in combination with mycophenolate mofetil (MMF) and low-dose glucocorticoids. The placebo-controlled group received MMF and low-dose glucocorticoids alone.

The long-term safety and efficacy of voclosporin was the primary study objective. Safety was evaluated by adverse events (AEs) and laboratory assessments (biochemical, hematologic). Tolerability was evaluated by the achievement of complete renal response (CRR), partial renal response (PRR), changes in urine protein creatinine ratio (UPCR), estimated glomerular filtration rate (eGFR), and serum creatinine.

A total of 186 patients completed the AURORA 2 trial; 101 patients from the voclosporin group and 85 from the control group. Pretreatment baseline clinical and demographic characteristics, as well as corrected mean eGFR, were similar between both the voclosporin and control groups.

The proportion of patients experiencing AEs (voclosporin, 86.2%; control group, 80.0%) and SAEs (voclosporin, 86.2%; control group, 80.0%) were comparable between both groups. Study drug discontinuation due to AEs was nearly double among the control group compared with the voclosporin group (17.0% vs 9.5%, respectively).

Mean corrected eGFR remained stable for the duration of the study period and was not statistically different between both groups. Mean eGFR at baseline and month 36 was 79.0 and 80.3 mL/min/1.73 m² among the voclosporin group vs 78.7 and 78.7 mL/min/1.73 m² among the control group, respectively.

Upon completion of AURORA 2, more patients in the voclosporin group vs the control group achieved CRR (50.9% vs 39.0%; odds ratio [OR], 1.74; 95% CI, 1.00-3.03) and PRR (74.1% vs 69.0%; OR, 1.39; 95% CI, 0.75-2.58).

A good renal outcome (defined as a sustained UPCR reduction of ≤0.7 mg/mg with no subsequent renal flare) was achieved by more patients in the volcosporin group vs the control group (66.4% vs 54.0%; OR, 0.56; 95% CI, 0.32-0.99).

This study was limited by possible selection bias.

The study authors concluded, “This analysis confirms the safety, tolerability, and efficacy of voclosporin reported previously, with no new or unexpected safety signals observed with an additional two years of treatment.”

Disclosure: One or more of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.