Voclosporin Plus MMF and Steroids Provide Superior Renal Response vs Placebo in Lupus Nephritis

taking pills
taking pills
Researchers aimed to evaluate the efficacy and safety of calcineurin inhibitor voclosporin for the treatment of lupus nephritis.

Among patients with lupus nephritis, a combination of voclosporin, mycophenolate mofetil (MMF), and low-dose steroids vs MMF and low-dose steroids alone provides a clinically and statistically superior renal response rate, according to study results published in the Lancet.

The double-blind, phase 3 trial (ClinicalTrials.gov Identifier: NCT03021499) was conducted in 142 hospitals and clinics across 27 countries. Patients with a diagnosis of lupus nephritis, according to the American College of Rheumatology (ACR) criteria, and a kidney biopsy within 2 years were eligible in the analysis. Patients were randomly assigned to receive 23.7 mg of oral voclosporin twice daily or placebo. All participants also received 1 g of MMF twice daily and rapidly tapered low-dose oral steroids. Renal response, as well as safety and efficacy, at 52 weeks was assessed.

The voclosporin and the placebo group included 179 and 178 participants, respectively. A total of 41% of the voclosporin group (n=73) and 23% of the placebo group (n=40) achieved the primary endpoint, ie, complete renal response at week 52 (defined as a composite of urine protein creatinine ratio of ≤0.5 mg/mg); odds ratio, 2.65; 95% CI, 1.64-4.27; P <.0001. Secondary endpoints were also statistically significant in favor of the voclosporin group.

Overall, the serious adverse events profile was similar between the 2 groups. Infections and infestations were the most common serious adverse events, with pneumonia being the most frequent. A total of 7 (4%) and 8 (4%) cases were recorded in the voclosporin and placebo groups, respectively. One patient in the treatment group and 5 in the placebo group died; however, these events were unrelated to the study treatments.

Study limitations included the lack of assessments of activity and chronicity indices; the lack of inclusion of information on MMF dose before enrollment; the fact that the response to treatment in patients with new-onset compared with relapsed lupus nephritis was not differentiated; and the lack of evaluations of extra-renal systemic lupus erythematosus activity. The study was also limited by the follow-up duration of 52 weeks with regard to a chronic condition like lupus nephritis.

According to investigators, the results of the analysis, “showed superior efficacy of voclosporin compared with placebo in combination with MMF and low-dose steroids, confirming the early treatment response and overall treatment efficacy observed with voclosporin in the phase 2 trial.” The improved efficacy in the voclosporin group was also achieved with a significantly lower cumulative steroid dose than in any previous study, they noted, adding that, the phase 2 and 3 results, “represent[ed] an important advancement in the treatment of patients with active lupus nephritis.”

Disclosure: The study was supported by Aurinia Pharmaceuticals. Please see the original reference for a full list of authors’ disclosures. 


Rovin BH, Onno Teng YK, Ginzler EM, et al. Efficacy and safety of voclosporin versus placebo for lupus nephritis (AURORA 1): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. Published online May 7, 2021. doi:10.1016/S0140-6736(21)00578-X