FTY720 immunomodulation: Optimism for improved transplant regimens

FTY720, a sphingosine 1-phosphate receptor (S1P-R) agonist, is the first in a new class of immunomodulators. FTY720 has been shown to be highly effective for preventing graft rejection in preclinical models of cardiac, renal, and hepatic transplantation. To date, phase I single and multiple dosing studies conducted in stable renal transplant patients have revealed a favorable efficacy and tolerability profile. Following these preliminary clinical evaluations, phase 11 studies have determined optimal dosing for prevention of acute rejection and the efficacy and tolerability of FTY720 in combination with reduced and full-dose cyclosporine (CsA). Data available for these studies demonstrate that FTY720 5 mg combined with reduced-dose CsA provides equivalent freedom from acute rejection to a standard mycophenolate mofetil (MMF)/CsA regimen. Moreover, rejection prophylaxis with a 5-mg dose of FTY720 appears to allow for a 50% reduction in the dose of calcineurin inhibitors while effectively preventing graft rejection. These studies have also shown that FTY720 has no overlapping toxicity with classical immunosuppressive agents; FTY720 can be used safely in combination with CsA and everolimus. Overall, these synergistic effects suggest that FTY720 has the potential to provide a real improvement in the efficacy and tolerability of future immunosuppressive regimens.