Drugs in development for prophylaxis of rejection in kidney-transplant recipients

Transplantation is the preferred treatment option for individuals with end-stage renal disease. Individuals who undergo transplantation must chronically be maintained on an immunosuppression regimen for rejection prophylaxis to help ensure graft survival. Current rejection prophylaxis consists of using a combination of calcineurin inhibitors, mTOR inhibitors, antimetabolite agents, and/or corticosteroids. These agents have collectively improved the short-term outcomes of renal transplantation, but improvements in late/chronic graft loss and recipient survival have lagged significantly behind challenging the field of transplantation to develop novel prophylactic agents. There have been several clinical trials conducted within the last 5 years in an attempt to bring such novel agents to the commercial market. These trials have resulted in the US Food and Drug Administration (FDA) approval of extended-release tacrolimus, as well as belatacept, which has the potential to replace calcineurin inhibitors for rejection prophylaxis. Other trials have focused on the development of novel calcineurin inhibitors (voclosporin), costimulation blockade (ASKP1240 and alefacept), kinase inhibitors (tofacitinib and sotrastaurin), and inhibitors of leukocyte migration (efalizumab). While these later agents have not been FDA-approved for use in transplantation, they remain noteworthy, as these agents explore pathways not previously targeted for allograft-rejection prophylaxis. The purpose of this review was to consolidate available clinical trial data with regard to the recent developments in rejection prophylaxis in kidney transplantation.