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An analysis of data from the phase 2 AURA-LV and phase 3 AURORA 1 trials provides new insight into the effects of voclosporin for the treatment of active lupus nephritis in patients with high proteinuria.
Use of voclosporin (Lupkynis) was associated with a significantly greater renal response in lupus nephritis patients with high proteinuria relative to mycophenolate mofetil (MMF) and low-dose steroids alone, according to a new analysis.
Presented at the European Congress of Rheumatology (EULAR) 2023, results of the study, which was a pooled analysis of phase 2 and phase 3 trials of voclosporin, suggest use of voclosporin in patients with biopsy-proven lupus nephritis with an urine protein creatinine ratio (UPCR) equal to or exceeding 2 mg/mg led to a greater proportion of patients achieving complete renal response, with this consistent across subgroups defined by age, sex, and race/ethnicity.
“Proteinuria is a common manifestation of [lupus nephritis] that can lead to progressive kidney damage. Early reductions in UPCR have been shown to be predictive of improved long-term outcomes in [lupus nephritis]. Yet, there remains the need for safe and effective therapies for patients with high proteinuria, especially given that monoclonal antibody therapies have demonstrated limited efficacy in LN patients with moderate to high proteinuria. These findings for voclosporin, a novel calcineurin inhibitor, are clinically relevant and can help improve renal outcomes for LN patients,” said lead investigator and study presenter Emily Littlejohn, DO, MPH, clinical assistant professor at the Cleveland Clinic and director of the Cleveland Clinic Lupus Cohort.2
In January 2021, the US Food and Drug Administration approved voclosporin in combination with a background immunosuppressive therapy regimen to treat adult patients with active lupus nephritis, which made it the first oral therapy approved by the agency. The 2021 approval was based on a clinical trial program sponsored by Aurinia, which concluded patients using voclosporin were more than twice as likely to achieve renal response and experienced a decline in UPCR twice as fast as their counterparts using standard of care alone.3
In the analysis presented by Littlejohn at EULAR 2023, sought to develop a greater understanding of the efficacy of voclosporin use among patients with high proteinuria from within the phase 2 AURA-LV and phase 3 AURORA 1 trials, which enrolled 268 and 266 patients, respectively. When limiting these populations to those with a baseline UPCR equal to or exceeding 2 mg/mg, investigators identified 217 and 215 patients from the AURA-LV and AURORA 1 trials, respectively. Investigators pointed out these groups had a mean UPCR of 5.2 (SD, 3.4) and 4.6 (SD, 2.9), respectively, at baseline.1
The primary outcome of interest for the investigators’ analysis was the proportion of patients achieving complete renal response, which was defined as a UPCR equal to or less than 0.5 mg/mg with stable renal function, low-dose steroids, and no rescue medications. Investigators noted plans for subgroup analyses based on sex, age, race, ethnicity, biopsy class, and eGFR at baseline.1
Upon analysis, results suggested the change from baseline to 1-year for least squares mean UPCR among the pooled voclosporin arm was —3.8 (SD, 0.1 mg/mg compared to —3.1 (SD, 0.2) mg/mg in the control arm (difference, —0.7; P =.0003). Further analysis indicated a significantly greater percentage of patient in the voclosporin arm achieved complete renal response at 1 year relative to their counterparts in the control arm (Odds Ratio, 2.48 [95% CI, ]; P < .0001).1
Subgroup analyses indicated complete renal response rates were greater in the voclosporin group than the control groups I both sexes and across all other subgroups, including biopsy classes and baseline eGFR groups. When assessing rates among biopsy classes, investigators found the highest rates of complete renal response were observed in Class III patients treated with voclosporin (50% vs 16.1% in controls; P = .0126), followed by Class IV (44% vs 23.8%; P = .0019), Class V with III or IV lesions (37.7% vs 17%; P = .0306), and Class V (31.3% vs. 28.6%; P = .81).1
“We are pleased to present these findings that further support the efficacy and safety of a voclosporin-based treatment regimen across diverse [lupus nephritis] patient populations. In this analysis, complete response rates favored voclosporin regardless of sex, race, ethnicity, baseline UPCR or baseline renal function. Patients who achieved complete renal response with voclosporin experienced stable renal function while undergoing a rapid steroid taper as part of the study. These findings further differentiate LUPKYNIS, a next-generation [calcineurin inhibitor], from legacy, first-generation [calcineurin inhibitors],” said Greg Keenan, MD, chief medical officer of Aurinia.2