Magazine article Drug Topics

New Immunosuppressive Drug Bulks Up Transplant Arsenal

Magazine article Drug Topics

New Immunosuppressive Drug Bulks Up Transplant Arsenal

Article excerpt

For those living with a transplanted organ, Rapamune (sirolimus/ rapamycin)-a newly approved immunosuppressive drug-may represent an added insurance policy against the risk of rejection.

Originally derived from the soil of Easter Island and now marketed by American Home Products (AHP), sirolimus is indicated for use in combination with cyclosporine and corticosteroids for the prevention of acute organ rejection in kidney transplant patients. Exerting its effects via a mechanism that is distinct from other immunosuppressive agents, sirolimus is known to bind to specific proteins and generate an immunosuppressive complex that, in turn, inhibits the activation of a key regulatory kinase known as mammalian Target of Rapamycin (mTOR). This inhibition suppresses cytokine-driven proliferation of T cells-essential components of the body's immune response.

Howard Marder, M.D., senior vp. of medical affairs and medical director at AHP, summed up the pharmacologic differences between sirolimus and calcineurin inhibitors (cyclosporine and tacrolimus) in basic terms: "The latter drugs reduce the syntheses of interleukin-2 (IL-2), while sirolimus makes cells refractory to IL-2 activity."

Approval of sirolimus was based on two prospective clinical trials; one compared the efficacy of sirolimus/ cyclosporine/prednisone with azathioprine/cyclosporine/prednisone, while the other compared the efficacy of sirolimus/cyclosporine/prednisone with cyclosporine/prednisone/placebo. Both trials evaluated sirolimus at 2 mg/day and at 5 mg/day. Results from these trials indicate that the sirolimus-containing combination reduced acute rejection rates by up to 60%, compared with the regimens containing cyclosporine and corticosteroids with either azathioprine or placebo. Graft loss and patient survival rates at six and 12 months were similar in the sirolimus- and comparator-treated patients. …

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