Once-daily version of Prograf

Extended-Release Tacrolimus Appears Safe, Effective

May 7, 2007 (San Francisco) — Patients undergoing transplantation may soon benefit from a less expensive, simpler immunosuppressive regimen, according to Harold Yang, MD, PhD, during a presentation here.

Dr. Yang, medical director of transplantation services at Pinnacle Health in Harrisburg, Pennyslvania, presented the 2-year follow-up findings of a phase 3 trial of extended-release tacrolimus at this year's American Transplant Congress. Extended-release tacrolimus is designed to be taken once per day in patients who have undergone kidney transplantation. Tacrolimus is already the most commonly used drug for immunosuppression in kidney transplants, but the currently approved form must be taken twice a day.

"It's tough to take a medication, period," Dr. Yang told Medscape. "But it's much easier if you only have to take it once a day."

In the trial, extended-release tacrolimus was compared with standard tacrolimus and cyclosporine, which also must be taken twice daily. The safety and efficacy of the 3 medications were similar during the 2-year follow-up period.

"We actually had wonderful patient and graft survival in all treatment groups," Dr. Yang said.

In this open-label trial, investigators randomly assigned 638 subjects in equal numbers to 1 of 3 treatment groups. All of the patients also received standard basiliximab induction, mycophenolate mofetil, and corticosteroids. A total of 513 patients completed the study at 60 centers in the United States, Canada, and South America. There were no significant differences in demographics among the 3 groups.

The patient survival rate after 2 years in the extended-release tacrolimus group was 97.6% compared with 93.6% in the standard tacrolimus group and 96.6% in the cyclosporine group.

Graft survival for the extended-release tacrolimus group was 93.7% compared with 89.9% in the standard tacrolimus group and 92.7% in the cyclosporine group.

The investigators also compared the biopsy-proven acute rejection (BPAR) rate among the 3 groups and found no statistical difference; the extended-release tacrolimus group had a BCAR rate of 12.9%, while the standard tacrolimus group's rate was 11.1% and the cyclosporine group's rate was 16.6%.

Investigators also found similar success rates among the 3 groups when they looked at mean serum creatinine, creatinine clearance, mean total cholesterol, and low-density lipoprotein cholesterol levels. Both of the tacrolimus groups fared better than the cyclosporine group in measurements of the use of antilymphocyte antibody therapy, the number of patients on lipid-lowering agents, and the number of patients who discontinued therapy. None of the patients developed any new cases of insulin-dependent diabetes mellitus between years 1 and 2.

This study comes as good news to transplant patients, A. Osama Gaber, MD, director of transplantation at the Methodist Hospital in Houston, told Medscape. "This is what transplant patients really want," he said. "It's easier, and they will have more freedom."

Dr. Gaber called the study "well-organized" and he predicted that extended-release tacrolimus will improve drug compliance in kidney transplant patients. "Missing medication is a very big issue, and it's probably underreported," he said.

The news is not just of interest to kidney patients, Dr. Yang said, because extended-release tacrolimus could be used in other organ transplantation as well. He predicted the drug will soon be approved by the US Food and Drug Administration.

The study was funded by Astellas, which markets tacrolimus under the brand name Prograf. Neither Dr. Yang nor Dr. Gaber has a financial relationship with the company.

ATC 2007: Abstract 144. Presented May 6, 2007.