horse antithymocyte globulin + sirolimus + cyclosporine

This investigational immunosuppressive combination therapy consists of horse antithymocyte globulin (h-ATG), sirolimus, and cyclosporine. Developed and studied by the National Heart, Lung, and Blood Institute (NHLBI), the regimen was designed to treat severe aplastic anemia (SAA) by utilizing three distinct but complementary mechanisms of T-cell inhibition. Horse ATG (Atgam) provides potent T-lymphocyte depletion, while cyclosporine (a calcineurin inhibitor) and sirolimus (an mTOR inhibitor) block T-cell activation and proliferation through synergistic pathways. Despite the theoretical advantage of adding sirolimus to the standard dual therapy of ATG and cyclosporine, a Phase 2 randomized trial (NCT00061360) was terminated early after interim analysis showed that the triple combination did not improve hematologic response rates in treatment-naive SAA patients.

Brand names

Rapamune

Other names

h-ATG + sirolimus + CsAATG + Rapamune + cyclosporineh-ATG + sirolimus + cyclosporineATG + sirolimus + cyclosporine