New Immunosuppressant for Kidney Transplant Patients Approved

Therapy Originally Derived from Soil of Easter Island Offers a New Treatment Option

Rapamune® (sirolimus), a new drug to help prevent acute rejection of transplanted kidneys, has been approved by the Food and Drug Administration (FDA).

"Rapamune represents a new alternative in immunosuppression. It will provide an important new treatment option for renal transplant patients, which is especially significant since there aren't many therapeutic choices," says Barry D. Kahan, Ph.D., M.D., professor of surgery, director, division of immunology and organ transplantation at The University of Texas-Houston Health Science Center. Dr. Kahan was the principal investigator of the clinical trials that led to the approval of Rapamune.

Discovered more than 25 years ago from the soil of Easter Island, Rapamune is recommended to be used in combination with cyclosporine and corticosteroids for the prevention of acute organ rejection in kidney transplant patients. Results from clinical trials demonstrate that Rapamune, when used in this combination, reduces acute rejection rates by up to 60 percent compared to control regimens.

Kidney transplantation is the most common type of transplant procedure in the United States. To help reduce the risk of organ rejection, transplant patients are given a life-long regimen of immunosuppressant agents. These drugs are intended to lower the body's normal immune response, allowing the transplanted organ to remain functional.

Immunosuppressant drugs are necessary after organ transplants because the human body is designed to reject cells that are foreign and perceived to be potentially dangerous, such as a transplanted organ. Thus, the very system that provides protection against intruding organisms is the system that poses a substantial threat to the transplant recipient.

Reducing the potential for organ rejection has become increasingly important due to a global shortage of donor organs available for human transplantation. There are currently more than 40,000 patients in the United States awaiting kidney transplants, and approximately 12,000 kidneys were transplanted in 1998.

"This shortage increases the importance that each organ transplant is successful, and that the medications to help support a successful outcome are optimal. Therefore, this new therapy holds particular promise in meeting this global challenge," notes Dr. Kahan.

Rapamune differs considerably from cyclosporine and tacrolimus, which are calcineurin inhibitors. Rapamune is the first of a distinctive class of immunosuppressants; Rapamune inhibits the activation of TOR (target of rapamycin), a key regulatory kinase involved in cell cycle progression.

Clinical data from two prospective, Phase III, double-blind, comparative studies demonstrated the efficacy and safety of Rapamune.

Dr. Kahan led the largest transplant clinical trial ever conducted in the United States involving kidney transplant patients. The trial involved 719 patients in the United States. Researchers compared the efficacy of Rapamune (2 mg/day and 5 mg/day) versus azathioprine. These groups also received cyclosporine and prednisone as a triple therapy regimen.

A second trial conducted among 550 patients in nine countries compared the efficacy of Rapamune (2 mg/day and 5 mg/day) plus cyclosporine and prednisone, versus cyclosporine and prednisone plus placebo.

Rapamune is associated with significant adverse side effects, Dr. Kahan stresses, including increased risk of infection and lymphoma due to immunosuppression. The drug may also increase blood pressure, plasma cholesterol and triglyceride levels, which could require medical intervention. Renal function should also be closely monitored, the FDA says.

Rapamune is made by Wyeth-Ayerst Laboratories in Philadelphia, a unit of the American Home Products Company.

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©2006 Texas Medical Center

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