To print: Select File and then Print from your browser's menu --------------------------------------------------------------------------------------- Title: Rapamune Improves Organ Survival, Reduces Rejection Rate URL: http://www.pslgroup.com/dg/8E896.htm Doctor's Guide July 14, 1998
MONTREAL, QC -- July 14, 1998 -- A new medication for preventing the body's immune system from rejecting organ transplants, Wyeth-Ayerst Pharmaceuticals' Rapamune(R) (sirolimus/rapamycin), demonstrated the first clinically-significant improvement in the survival of transplanted kidneys since 1983, according to data presented today at the 17th world congress of The Transplantation Society. "These findings represent a clinically meaningful advance in the field of transplantation. For the first time since cyclosporin was introduced fifteen years ago, we have clearly demonstrated the ability of an immunosuppressive drug to improve graft survival rates," said lead investigator Barry Kahan, Ph.D., M.D., of The University of Texas-Houston Health Science Center. The Phase III clinical trials compared the efficacy of sirolimus/rapamycin (2 mg/day and 5 mg/day) versus azathioprine, administered concomitantly with standard immunosuppressive therapy (cyclosporin and prednisone), in patients receiving kidney transplants. More than 700 kidney transplant patients participated in the randomised, double-blinded, race-stratified study conducted at more than 40 centres across the United States, making it the largest transplant study ever conducted. Graft loss or the physical loss of the transplanted organ was lowest among patients in the lower dose, 2 mg/day sirolimus/rapamycin treatment group. In fact, only two percent of patients on 2-mg/day sirolimus/rapamycin experienced graft loss, whereas six percent of patients in the control group experienced graft loss. "In addition to these findings, patients treated with sirolimus/rapamycin experienced significantly fewer episodes of acute rejection and, when they did, the episodes were markedly less severe," Dr. Kahan explained. Importantly, patients treated with sirolimus/rapamycin showed a 60 to 70 percent reduction in acute rejection. Only 10 percent of the patients treated with 5 mg/day of sirolimus/rapamycin and 15 percent of the 2 mg/day patients, experienced acute rejection episodes, compared to 24 percent of patients treated with the standard azathioprine, cyclosporin, prednisone regimen. Furthermore, the study confirmed that treatment with sirolimus/rapamycin reduced the requirement for antibody therapy to reverse rejection episodes. Antibody therapy is costly and can also cause other complications. Organ transplantation became a true medical option beginning as recently as the 1980s, with the introduction of cyclosporine. However, despite the progress that has been made, cyclosporine and other standard therapies result in a range of complications, including viral, fungal and bacterial infections, as well as increasing the risk of certain cancers. Additionally, these regimens often carry devastating toxicities, including renal and neural toxicity and other serious adverse events. Research has shown that many of the toxic side effects associated with cyclosporin and a similar compound, FK-506, are caused by their mechanism of action to inhibit calcineurin activity in non-immune cells. Sirolimus/rapamycin works by a novel mechanism to selectively block proliferation of T cells, which are essential components in the body's immune response. Because of its unique mechanism of action, sirolimus/rapamycin does not affect calcineurin, which may mean less, if any of these toxicities in patients treated with sirolimus/rapamycin. "While we've come a long way to making transplantation a routine and highly effective treatment of renal disease, liver failure and heart failure, patients often have to bear the burden of difficult and, at times, serious complications related to current therapies," Dr. Kahan said. "The emergence of a new compound that does not cause these effects brings hope to patients who have already undergone a transplant procedure and those who will follow." Kidney transplantation is the most common type of transplant procedure in the U.S., although there is a significant shortage of available organs. As there is a scarcity of donor organs and the body's immune system is naturally programmed to reject transplanted organs, it is critical that patients receive the optimal medical therapy to ensure the survival of the organ without harming the patient. At present, the largest single group of patients being listed for transplants are those with previously failed transplants. As an immunosuppressant, sirolimus/rapamycin prevents the body from rejecting a transplanted kidney, when used in combination with low doses of cyclosporin. Derived from the soil of Easter Island -- Rapa Nui to native islanders and also the origin of the molecule's name -- the active molecule rapamycin was found to selectively block proliferation of T cells, which are essential components in the body's immune response. Sirolimus/rapamycin is the first base-line immunosuppressive that does not affect calcineurin activity. Based on data derived from this study, the long-term benefit of sirolimus/rapamycin is currently being evaluated. In this landmark pivotal Phase III study, as well in Phase I and II trials conducted earlier, sirolimus was well-tolerated and exhibited no apparent nephrotoxic properties or adverse effects on blood pressure. --------------------------------------------------------------------------------------------- Copyright © 1999 P\S\L Consulting Group Inc. 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