Organ transplant patients may soon be able to benefit from a promising alternative to standard calcineurin inhibitor (CNI) based immunosuppressive regimens, according to a new study presented at this year's American Transplant Congress (ATC).

The multicentre, prospective Phase II study of 52 kidney transplant patients at high risk of delayed graft function (DGF) showed that a combination of the Novartis investigational agents FTY720 (a lymphocyte-homing agent which reversibly redirects lymphocytes away from the graft) and Certican (a proliferation inhibitor which targets primary causes of chronic rejection), together with standard corticosteroids, achieved immunosuppressive efficacy comparable to that seen with CNI-based regimens, without the risk of nephrotoxicity often associated with CNI use.

Lead investigator Dr Marc I. Lorber, professor of surgery and chief, section of organ transplantation and immunology at the Yale University School of Medicine, commented: "The patients in this study were all at high risk of experiencing delayed graft function, a situation associated with a deleterious effect on ultimate graft survival. To that end, they represented a particularly vulnerable group. Nonetheless, the incidence of graft loss and acute rejection seen to date compared favourably with the rates usually seen with more conventional CNI-based regimens in this difficult patient population. Importantly, the FTY720 / Certican regimen resulted in good renal function in these high risk patients, with serum creatinine levels comparable to those expected in a low risk group. This approach may offer a viable alternative to CNI-based immunosuppression among patients at risk of DGH.

FTY720 is a completely novel therapeutic agent with a highly selective mode of action. Through its targeted lymphocyte homing activity, FTY720 is expected to protect the graft from T-cell mediated damage, while leaving other aspects of the immune response unimpaired and thus still able to ward off systemic infections. Pre-clinical studies have shown that the host's response to infectious challenge is not impaired by FTY720.

Furthermore, in clinical trials, treatment with FTY720 was associated with a low incidence of regimen-related adverse events. A negative chronotropic effect (bradycardia) has been observed previously in patients being treated with FTY720, and in this study was reported in 10% of patients. Bradycardia associated with FTY720 treatment is generally transient, mild, and recovers spontaneously in the majority of patients.

In a second FTY720 clinical study presented at this year's ATC, it was demonstrated that, in contrast to most other immunosuppressants, therapeutic drug monitoring is not required during FTY720 administration, potentially increasing ease of use for the patient and the physician.

Novartis is currently exploring further the possibility of CNI-free regimens in animal models. A study of the combination of FTY720 with Myfortic - a gastroprotective formulation of the immunosuppressant mycophenolic acid - was shown to be promising and to merit further investigation.

"FTY720 is being actively investigated in renal transplant patients and accumulating results suggest this agent may represent an important advance in our efforts to provide more effective, better tolerated and safer immunosuppression", Dr Lorber said.