FDA Approves Tacrolimus for Use With MMF in Kidney Transplant Recipients

Yael Waknine

June 04, 2009

June 4, 2009 — On May 19, the FDA approved an expanded indication for tacrolimus (Prograf capsules and injection, Astellas Pharma US, Inc), recommending its use with mycophenolate mofetil (MMF) for the prophylaxis of organ rejection in allogenic kidney transplantation.

"Prograf + MMF has been an accepted and successful immunosuppressant regimen for the transplant community for more than 10 years," said Flavio Vincenti, MD, professor of clinical medicine, Division of Nephrology, University of California, San Francisco, in a company news release. "This FDA approval recognizes the most commonly used regimen of transplant centers and reinforces the importance of this combination therapy in the treatment of kidney and heart transplant recipients."

The FDA's decision was based in part on data from a phase 3, multicenter, open-label clinical trial (n = 424) showing that use of tacrolimus/MMF and cyclosporine/MMF, in combination with basiliximab induction and corticosteroids, yielded similar rates for the combined endpoint of biopsy-proven acute rejection, graft failure, death, and/or lost to follow-up at 1 year (tacrolimus/MMF, 15.1%; cyclosporine/MMF 17.0%).

Study results also revealed an imbalance in 1-year mortality rates for patients receiving tacrolimus/MMF (4.2%) compared with those receiving cyclosporine/MMF (2.4%), including cases attributed to overimmunosuppression.

Another study, which was a randomized, open-label, multicenter trial (ELITE-Symphony; n = 1589) revealed similar 1-year mortality rates.for tacrolimus/MMF plus daclizumab induction and corticosteroids (2.7%) compared with the following treatment groups:

  • standard-dose cyclosporine/MMF plus corticosteroids (3.3%);

  • low-dose cyclosporine/MMF with daclizumab induction and corticosteroids (1.8%);

  • and sirolimus/MMF with daclizumab induction and corticosteroids (3.0%).

Results also showed that patients in the tacrolimus group exhibited improved kidney function relative to the other treatment groups, as defined by estimated creatinine clearance rates (66.2 mL/minute vs 56.9 – 60.9 mL/minute).

Tacrolimus-treated patients in the study were also less likely to experience efficacy failure, defined as biopsy-proven acute rejection, graft loss, death, and/or lost to follow-up at 1 year compared with the other treatment groups:

  • tacrolimus/MMF/daclizumab, 20.4%;

  • standard-dose cyclosporine/MMF/corticosteroids, 36.2%;

  • low-dose cyclosporine/MMF/daclizumab/corticosteroids, 31.6%; and

  • sirolimus/MMF/daclizumab/corticosteroids, 46.4%.

Patients randomly assigned to receive tacrolimus/MMF/daclizumab/corticosteroids were also more likely to develop diarrhea and diabetes after the transplantation and experienced similar rates of infections compared with patients randomly assigned to receive either cyclosporine/MMF regimen.

Tacrolimus is approved by the FDA for the prophylaxis of organ rejection in patients receiving allogenic liver, kidney, or heart transplants. Concomitant use of adrenal corticosteroids and azathioprine or MMF is recommended for kidney and heart transplant recipients.

The ELITE-Symphony study was supported by Hoffmann La Roche, Inc.