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Data from an analysis of kidney biopsies from the AURORA 2 trial presented at CCR East 2023 offer new insight into the long-term histological impact of voclosporin use on renal function in patients with lupus nephritis.
An analysis of data obtained from follow-up kidney biopsies of AURORA 2 participants is shedding further light into the long-term effects of voclosporin (Lupkynis) on renal function in patients with lupus nephritis.
Presented at the Congress of Clinical Rheumatology (CCR) East 2023 annual meeting, results of the study, which included biopsy data from 16 patients in the voclosporin arm and 10 from the placebo arm, indicate use of the agent was associated with decreased disease activity scores and a higher rate of patients achieving either complete or partial resolution, with efficacy results non this subgroup consistent with the overall study population.1
“This is the first study involving voclosporin that assessed histologic changes in the kidney with lupus nephritis. Activity scores decreased in conjunction with UPCR improvement in both treatment arms,” wrote investigators.1 “Exposure to voclosporin did not increase chronic injury.”
Approved in January 2021 for treatment of active lupus nephritis in adult patients, voclosporin became the first oral therapy to receive such an indication from the US Food and Drug Administration. Examined in the phase 3 AURORA 1 and AURORA 2 studies, the calcineurin-inhibitor immunosuppressant was found to be associated with significantly earlier and greater reductions in proteinuria without composing renal function.2
Despite the approval and positive trial results, the long-term histological impact of use on renal function has not been fully elucidated. With this in mind, a team led by Samir Parikh, of the Ohio State University Wexner Medical Center, and colleagues sought to better understand the effects of voclosporin use in people with lupus nephritis through an analysis of data obtained from follow-up kidney biopsies among members of the AURORA-2 cohort.
A 52-week, randomized, double-blind placebo-controlled trial, the phase 3 AURORA 2 study, which enrolled study subjects from AURORA 1, was designed with the intent of assessing the long-term safety and tolerability of voclosporin compared against placebo for up to an additional 24 months. A total of 216 patients continued from AURORA 1 into AURORA 2, with 116 patients in the voclosporin-treated group and 100 in the control group.3
Per trial protocol, AURORA 2 participants continued the same randomized treatment of voclosporin at 23.7 mg twice daily or placebo, in combination with mycophenolate mofetil at 1 g twice daily with low-dose oral steroids, for up to an additional 24 months. Results of the study, which were presented at the 59th European Renal Association Congress in May 2022, indicated patients were able to maintain the reduction in proteinuria achieved in AURORA 1 and a significant difference in eGFR slope in favor of voclosporin (-0.2 mL/min/1.73m2) relative to the control arm (-5.4 mL/min/1.73m2) of the trial.3
In the current study, investigators hoped to leverage renal biopsies performed as part of the AURORA 2 study to better understand the long-term impact of voclosporin use. With this in mind, investigators chose mean urine protein creatinine ratio (UPCR) over time as well as complete renal response and partial renal response to serve as the primary endpoints of interest. For the purpose of analysis, investigators defined a complete renal response as an UPCR equal to or less than 0.5mg/mg, state eGFR, low-dose steroids, and no rescue medication while partial renal response was defined as a reduction in UPCR of 50% or greater from baseline.1
Results of the investigators’ analyses indicated baseline activity scores were similar between treatment arms, with scores in both arms decreasing with treatment. Results suggested chronicity scores between the arms were also similar at baseline and remained stable throughout the duration of the study among most participants. Investigators pointed out there were no differences observed between the voclosporin-treated and placebo-treated arms in activity or chronicity scores at baseline or at repeat biopsy.1
Investigators also highlighted the mean eGFR values remained stable in both treatment arms throughout the course of the study and greater rates of both complete renal response and partial renal response were observed in patients treated with voclosporin at month 36.1