New Calcineurin Inhibitor Shows Promise

Voclosporin, a novel calcineurin inhibitor, compares well with tacrolimus in primary kidney transplant recipients—including a possible reduction in new-onset diabetes after transplantation (NODAT), reports a trial in the American Journal of Transplantation.

The phase 2, open-label trial included 334 low-risk patients undergoing initial renal transplantation. Patients were randomly assigned to receive low, intermediate, or high doses of voclosporin or standard-dose tacrolimus. At 6 months, the rates of biopsy-proven acute rejection were 10.7 percent, 9.1 percent, and 2.3 percent in the low- to high-dose voclosporin groups compared with 5.8 percent in the tacrolimus group. This was within the study margin of noninferiority.

Analysis of secondary outcomes found a significant reduction in NODAT with voclosporin: 1.6 percent, 5.7 percent, and 17.7 percent, compared with 16.4 percent with tacrolimus. The high-dose voclosporin group had a small but significant increase in estimated GFR compared with those receiving tacrolimus. Pharmacokinetic and pharmacodynamic studies showed excellent correlation between the voclosporin trough and area under the curve. There were no significant differences in mycophenolic acid exposure.

Voclosporin was developed as a new calcineurin inhibitor for organ transplantation that would reduce toxicity with similar or better efficacy. The new trial suggests that voclosporin is noninferior to tacrolimus in preventing acute rejection after de novo kidney transplantation. Further trials are needed to confirm these results, including the effects on renal function and NODAT risk [Busque S, et al. The PROMISE study: a phase 2b multicenter study of voclosporin (ISA247) versus tacrolimus in de novo kidney transplantation. Am J Transpl 2011;11:2675–2684].

March 2012 (Vol. 4, Number 3)