Background/Purpose: Voclosporin (VCS) is a novel calcineurin inhibitor, structurally similar to cyclosporine A (CsA). In a Phase 3 clinical trial in patients with active lupus nephritis (AURORA 1), patients treated with VCS in combination with MMF, achieved renal response rates of 40.8% vs. 22.5% for the control arm (OR 2.65; p < 0.001). Drug-drug interactions have been demonstrated between CsA and MMF, where CsA interferes with MPA recirculation resulting in up to 50% lower exposure to mycophenolic acid (MPA), the active metabolite of MMF. While VCS did not demonstrate a negative impact on MPA levels in transplantation, the primary objective of this study was to investigate the effect of VCS on MPA levels in subjects with systemic lupus erythematosus (SLE), with or without lupus nephritis.

Methods: Twenty-five subjects with Systemic Lupus Erythematosus, treated with MMF at an oral dose of 1 g BID for at least 28 days prior to screening were enrolled and continued at the same dose throughout the study. Voclosporin was administered at a dose of 23.7 mg BID for seven consecutive days, starting in the evening of Day 1 and ending with the morning dose on Day 7.  Blood samples for PK analysis of MPA and mycophenolic acid glucuronide (MPAG) were were collected at pre-am. doses and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 3, 4, 5, 6, 8, 10, and 12 hours post-a.m. doses after the morning dose of both drugs on Day 1 and 7. Analyses were performed using Phoenix™ WinNonlin® (Version 6.3)

Results: MPA exposure parameters were similar in the absence and presence of VCS (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]). The median time to Tmax was similar on both days, with comparable ranges of individual values. MPAG exposure showed a small increase in the presence of VCS (12% for Cmax and 27% for AUC0-12). Voclosporin exposure was consistent with previous studies. Administration of VCS with MMF over 7 days was well tolerated

Conclusion: There is no clinically meaningful interaction between voclosporin and MMF. As changes in exposure to MPA may affect its efficacy and safety, these data confirm that VCS and MMF can be given concomitantly without the need to adjust MMF dose

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/voclosporin-does-not-decrease-mycophenolic-acid-concentrations-in-patients-with-sle/