Five-year safety and efficacy of belatacept in renal transplantation

Abstract

Belatacept is a first-in-class co-stimulation blocker in development for primary maintenance immunosuppression. A Phase II study comparing belatacept with cyclosporine (CsA) for prevention of acute rejection and protection of renal function in kidney transplant recipients demonstrated similar efficacy and significantly higher measured GFR at 1 year for belatacept, but the incidence of posttransplantation lymphoproliferative disorder was higher. Here, we present the results for the extension of this trial, which aimed to assess long-term safety and efficacy of belatacept. Seventy-eight of 102 patients who were receiving belatacept and the 16 of 26 who were receiving CsA completed the long-term extension period. GFR remained stable in patients who were receiving belatacept for 5 years, and the incidences of death/graft loss or acute rejection were low. The frequencies of serious infections were 16% for belatacept and 27% for CsA, and neoplasms occurred in 12% of each group. No patients who were treated with belatacept and one patient who was treated with CsA developed posttransplantation lymphoproliferative disorder during the follow-up period. Serious gastrointestinal disorders occurred more frequently with belatacept (12% belatacept versus 8% CsA), and serious cardiac disorders occurred more frequently with CsA (2% belatacept versus 12% CsA). Pharmacokinetic analyses showed consistent exposure to belatacept over time. CD86 receptor saturation was higher in patients who were receiving belatacept every 4 weeks (74%) compared with every 8 weeks (56%). In conclusion, this study demonstrated high patient persistence with intravenous belatacept, stable renal function, predictable pharmacokinetics, and good safety with belatacept over 5 years.

Figures

Figure 1.

High participation and retention of belatacept-treated patients in the LTE.

Figure 2.

Stable renal function in belatacept-treated patients over time. Calculated GFR (based on the MDRD formula) was assessed at 6-month intervals in treated patients who reached the indicated time points. Data are means ± SD.

Figure 3.

Low occurrence of death or graft loss in belatacept-treated patients over time. The Kaplan-Meier plot is for all randomly assigned and transplant recipients in the ITT population without cancer over 60 months. Meddra 11.0 was used for skin and organ cancer; Meddra 10.0 was used for PTLD. Patients with events of cancer including skin, organ cancer, or PTLD were excluded.

Figure 4.

Higher exposure and CD86 receptor saturation with 4-week belatacept dosing. (A) Belatacept serum concentration was measured in subsets of LTE long-term extension patients on 4- and 8-week schedules during one dosing interval (5 mg/kg at 0 hours). Concentration of belatacept is indicated on the y axis (semilog scale). Data are means ± SD. (B) The graph shows the amount of free CD86 (HA5 binding) on monocytes from whole blood. Each dot represents an individual sample; some patients contributed more than one sample.