Voclosporin safe and efficacious for long-term use in managing lupus nephritis patients: AURORA 2 Trial

Nearly 50 % of patients with a history of systemic lupus erythematosus (SLE) suffer from Lupus nephritis (LN). The likelihood of mortality is heightened six- to nine-fold in individuals affected by LN and 14- to 26-fold in individuals affected by SLE with renal impairment. Disease management should slow down or stop the progression to end-stage kidney disease is essential. Voclosporin, a novel calcineurin inhibitor (CNI), is approved in the US and Europe for treating adult patients with active LN in combination with background immunosuppression.

A recent study published in Arthritis and Rheumatology has concluded that Long-term voclosporin is safe and efficacious for treating lupus nephritis over three years. No unexpected safety signals were reported during this period, and patients had better outcomes, including renal function stability, says Dr Saxena, lead author of the study.

AURORA 2 clinical trial evaluated the long-term safety, tolerability, and efficacy of voclosporin compared to placebo in patients with LN receiving an additional two years of treatment after completing the one-year AURORA 1 study. Enrolled patients continued their double-blinded treatment of voclosporin or placebo randomly assigned in AURORA 1, in combination with mycophenolate mofetil and low-dose glucocorticoids. The researchers in this study assessed safety with adverse events (AEs). Biochemical and haematological assessments were also done, and the renal response measured efficacy.

Key results of the study are:

· AURORA 2 trial had 216 patients.

· 86.1 % of patients completed the study. Treatment was well-tolerated. No unexpected safety signals were reported.

· In voclosporin and control groups, AE was experienced by 86% and 80% of patients, respectively. AE profile was similar to AURORA 1, albeit with reduced frequency.

· Compared to the control group, the Investigator reported that AEs of both glomerular filtration rate (GFR) decreased, and hypertension occurred more frequently in the voclosporin group.

· For both the treatment groups, mean eGFR was within the normal range and was stable.

· In voclosporin and the control group, the eGFR slope over the two years was −0.2 mL/min/1.73 m2 and −5.4 mL/min/1.73 m2, respectively.

· Across three years of treatment, there was evidence of persistent improved proteinuria causing more frequent complete renal responses in voclosporin-treated patients with an OR of 1.74.

AURORA 2 was a double-blinded, placebo-controlled, phase 3 trial that lasted for two years and served as a continuation of the pivotal AURORA 1 study. The trial aimed to evaluate the safety and tolerability of voclosporin over a three-year treatment period in LN patients. The trial results showed that voclosporin was effective in achieving a good renal outcome, with significantly more patients in the voclosporin group achieving this outcome than those in the control group.

Concluding further, the team said, over a follow-up duration of 3 years, we found the long-term voclosporin treatment profile to be safe and efficacious in Lupus nephritis patients.

The outcomes achieved with voclosporin treatment are beneficial. Overall, three-year data further supports voclosporin use with MMF and low-dose glucocorticoids for treating LN.

Reference:

Saxena, A., Ginzler, E. M., Gibson, K., Satirapoj, B., Santillan, A., Levchenko, O., Navarra, S. V., Atsumi, T., Yasuda, S., Chávez-Pérez, N., Arriens, C., Parikh, S., Caster, D. J., Birardi, V., Randhawa, S., Lisk, L., Huizinga, R. B., & Teng, Y. K. O. (2023). Safety and efficacy of long‐term voclosporin treatment for lupus nephritis in the Phase 3 AURORA 2 clinical trial. Arthritis & Rheumatology. https://doi.org/10.1002/art.42657