Voclosporin: a novel calcineurin inhibitor without impact on mycophenolic acid in patients with SLE

Background An open-label phase 1 study was conducted to evaluate the effect of voclosporin on blood levels of mycophenolic acid (MPA, active moiety) and mycophenolic acid glucuronide (MPAG, pharmacologically inactive metabolite) following dosing with mycophenolate mofetil (MMF) in subjects with systemic lupus erythematosus (SLE) and to assess the safety and tolerability of the combination. Methods MMF was orally administered at a dose of 1 g BID for at least 28 days prior to the study and continued at the same dose throughout the study. Voclosporin was orally administered at a dose of 23.7 mg BID for seven consecutive days (Day 1 to Day 7), starting in the evening of Day 1 and ending with the morning dose on Day 7. Dense PK blood samplings were collected pre-dose in the morning and from 0.25 to 12 hours post-morning doses. Analyses were derived by non-compartmental methods. Results In 24 patients, MPA exposure (Cmax and AUC0-12) was similar in the presence and absence of voclosporin, with treatment ratios of 0.94 and 1.09, respectively (Cmax: 16.5 μg/mL [Day 1] vs.15.8 μg/mL [Day 7], AUC0-12: 39.1 μg.h/mL [Day 1] vs. 40.8 μg.h/mL [Day 7]. MPAG exposure showed a small increase in the presence of voclosporin (12% for Cmax and 27% for AUC0-12). Combination therapy was well tolerated. Conclusions There is no clinically meaningful interaction between voclosporin and MMF. As changes in exposure to MPA may affect efficacy and safety, these data confirm that voclosporin and MMF can be given concomitantly without the need for dose adjustment.