In clinical trials, voclosporin demonstrated significantly improved renal response rates compared with mycophenolate mofetil and low-dose steroids. Voclosporin-treated patients were more than twice as likely to have a decline in their urinary protein creatinine ratio than patients on standard therapy alone. Additionally, this improvement occurred twice as fast in voclosporin-treated patients than in patients treated with standard therapy.
Background: The U.S. approval of voclosporin was based on multi-national clinical trials, including the AURORA-1 phase 3 and AURA-LV phase 2 studies.7-9 The AURORA 1 and AURA-LV studies were conducted in similar patient populations and with similar study designs.7 These were double-blind, placebo-controlled, randomized trials comparing two doses of voclosporin (23.7 mg or 39.5 mg twice daily) with patients treated with placebo combined with mycophenolate mofetil (2 grams daily), and rapidly tapered low-dose corticosteroids for induction of lupus nephritis remission. AURORA-1 was conducted over 52 weeks in 357 patients from 27 countries, while AURA-LV was conducted over 48 weeks in 265 patients from 20 countries. The primary endpoint in both studies was a renal response, which was defined as a urinary protein creatinine ratio of ≤0.5 mg/mg, eGFR ≥60 mL/min, no confirmed decrease from baseline in eGFR of more than 20%, less than 10 mg/d prednisone for at least eight weeks prior to endpoint assessment and no administration of rescue medication. The urinary protein creatinine ratio was measure in two consecutive, first-morning-void urine specimens.
In AURA-LV, the primary endpoint was evaluated at week 24 and week 48.8 The renal response at week 24 was attained in 32.6% (n=29) of patients who received 12.7 mg voclosporin twice daily (i.e., the low-dose group) and 27.3% (n=24) of patients who received 39.5 mg voclosporin twice daily (i.e., the high-dose group), compared with 19.3% (n=17) of patients who received placebo (OR=2.03; 95% CI 1.01–4.05; P=0.046). The statistically significant greater renal response in the patients who received low-dose voclosporin was maintained until week 48 (P<0.001 for low-dose voclosporin compared with placebo). Renal response was also significantly more common in the patients who received high-dose voclosporin than in those patients who received placebo at week 48 (P=0.046).
More serious adverse events occurred in patients treated with voclosporin (both doses). Infections and infestations occurred in 12.4% (n=11) of patients who received low-dose voclosporin, in 13.6% (n=12) of patients who received high-dose voclosporin, and in 8% (n=7) of patients who received placebo. !irteen patients died during the study. More deaths occurred in patients who received low-dose voclosporin (n=10; 11.2%) than among patients who received high-dose voclosporin (n=2; 2.3%) and among those patients who received placebo (n=1; 1.1%).
