FDA advisory panel recommends approval of Belatacept

Belatacept is a costimulation blocker that acts by binding to CD80 and CD86 on antigen presenting cells. Phase II (Vincenti et al NEJM 2005) and Phase III (BENEFIT Study Vincenti et al AJT 2010) trials showed that Belatacept patients (as compared to those receiving Cyclosporine) have comparable graft/patient survival, superior renal function with less fibrosis and better cardiovascular risk profile (lower risk of diabetes, hypertension and hyperlipidemia) at 12 months. Other advantage with Belatacept is that it is given as IV infusion every few weeks and so no issues with compliance as compared to BID PO Cyclosporine. However, the downsides are higher rate of acute cellular rejection (ACR) and posttransplant lymphoproliferative disease (PTLD). ACR is likely result of dual blockade of CTLA-4 dependent immunoregulatory pathway. PTLD mainly occured in EBV-negative recipients recieving EBV-positive kidneys. The other caveat is that there is no data on outcomes beyond 12 months follow-up.