The findings of the AURORA 2 phase 3 trial published in the recent issue of Arthritis & Rheumatology have reported the long-term safety, tolerability, and efficacy of voclosporin treatment over 3 years. Patients with lupus nephritis (LN) receiving an extra two years of treatment after the one-year AURORA 1 study’s completion were included in AURORA 2.
Dr. Amit Saxena and his team evaluated the safety and long-term efficacy of voclosporin in 216 individuals with LN. Around 86% of the participants completed the study. The medication was found to be well tolerated, and long-term treatment did not provide any new safety signals. In comparison to the placebo, voclosporin group experienced both glomerular filtration rate reduction and hypertension adverse events more frequently (10.3% vs. 5% and 8.6% vs. 7%) than the controls. Furthermore, improved proteinuria was sustained in patients receiving voclosporin treatment throughout the three years, leading to more frequent complete renal responses (50.9% vs. 39.0%; odds ratio 1.74; 95% CI 1.00, 3.03).
Data from 2022 AURORA 2 continuation study has reported that voclosporin was safe and well-tolerated, with a safety profile similar to the control over the course of three years of treatment. Additionally, even without the use of conventional high-dose steroids, AURORA 2 maintained the significant reductions in proteinuria that were first attained in AURORA 1.
In AURA-LV, two doses of voclosporin (23.7 mg or 39.5 mg, each twice daily) were compared to placebo in a phase 2 multicenter, randomized, double-blinded, placebo-controlled trial. This study compared the induction of remission in LN along with mycophenolate mofetil (2 g/d) and rapidly tapered low-dose oral corticosteroids. Complete renal remission (CRR) at 24 weeks was the primary goal, and CRR at 48 weeks was the secondary endpoint. CRR was attained by 32.6% of individuals in the study in week 24. At week 24, 32.6% of the low-dose voclosporin group’s patients, 27.3% of the high-dose voclosporin group’s subjects, and 19.3% of the placebo group’s subjects all obtained CRR (OR=2.03 for low-dose voclosporin vs. placebo). These findings indicate that, when mycophenolate mofetil and corticosteroids are combined with low-dose voclosporin for the induction therapy of active LN, the renal response is superior to that of mycophenolate mofetil and corticosteroids alone.
The current phase 3 trial underscores the potential of voclosporin as a valuable therapeutic option for LN patients, offering a well-tolerated and effective long-term treatment strategy. Further research and clinical trials are warranted to better understand the optimal dosing regimens and potential benefits of voclosporin in the treatment of LN.
References
- Saxena A, Ginzler EM, Gibson K, Satirapoj B, Zuta Santillan AE, Levchenko O, et al. Safety and efficacy of long‐term voclosporin treatment for lupus nephritis in the Phase 3 AURORA 2 clinical trial. Arthritis & Rheumatology. 2023 Jul 19
- Gibson K, Teng Y, Hodge L, Collins C. S06.2 Long-term efficacy and safety of voclosporin with mmf and low-dose steroids: data from the aurora 2 continuation study. Lupus Science & Medicine. 2022 Oct 1;9(Suppl 2).
- Rovin BH, Solomons N, Pendergraft III WF, Dooley MA, Tumlin J, Romero-Diaz J, et al. A randomized, controlled double-blind study comparing the efficacy and safety of dose-ranging voclosporin with placebo in achieving remission in patients with active lupus nephritis. Kidney international. 2019 Jan 1;95(1):219-31.