Enteric-coated mycophenolate sodium: therapeutic equivalence to mycophenolate mofetil in de novo renal transplant patients

Abstract

The introduction of mycophenolate mofetil (MMF)—the morpholino ester prodrug of mycophenolic acid (MPA)—has improved graft and patient survival, but its use has been linked with the occurrence of adverse events, particularly gastrointestinal (GI) side effects. These can be sufficiently severe to require dose reductions or discontinuation, which may lead to acute rejection episodes or graft failure. An enteric-coated formulation delivering mycophenolic acid—enteric-coated mycophenolate sodium (EC-MPS)—has been developed with the aim of improving upper GI tolerability. Therapeutic equivalence of EC-MPS 720 mg b.i.d. vs MMF 1000 mg b.i.d. has been established in a pivotal phase III, 12-month, international, randomized, double-blind, parallel group study, involving patients undergoing de novo renal transplantation. The incidence of efficacy failure (composite variable of biopsy-proven acute rejection [BPAR], graft loss, death or loss to follow-up) was similar between the two groups at 6 months (EC-MPS 25.8% vs MMF 26.2%; 95% CI [−8.7, +8.0]), demonstrating therapeutic equivalence. Efficacy failure remained similar between the two treatment groups at 12 months. The overall incidence of adverse events and GI side effects were also comparable between treatment groups throughout the 12-month study period, although fewer patients in the EC-MPS group experienced study drug discontinuations, interruptions, or dose reductions (12 months: EC-MPS 15.0% vs MMF 19.5%). Subgroup analysis revealed similar safety profiles for EC-MPS and MMF in elderly patients and patients with diabetes at baseline. The EC-MPS 720 mg b.i.d. and MMF 1000 mg b.i.d. show therapeutic equivalence in de novo renal transplant patients. Therefore, EC-MPS offers transplant physicians and their patients an alternative MPA therapy that is as effective and safe as MMF.