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