FK778, a novel compound with multiple modes of action - a breakthrough in transplant immunosuppression?

VENICE (Italy) September 24 (PROTEXT/PRNewswire) - First clinical data presented today at the 11th Congress of the European Society for Organ Transplantation in Venice suggest FK778, a novel compound with multiple mechanisms of action, is efficacious, well tolerated and safe in kidney transplant patients, potentially offering a breakthrough in immunosuppressive therapy. FK778 is the first of a new class of low molecular weight immunosuppressants, the malononitrilamides, currently under development for organ transplantation. In animal models, FK778 has been shown to block both cellular (T cell) and humoral (antibody) immune responses, potentially allowing FK778 to prevent not only acute rejection but also chronic allograft dysfunction - notoriously difficult to treat and one of the main reasons for late graft loss. Final results of the Phase II study (1)(n=149 adult renal transplant recipients) revealed that after 4 months treatment FK778 was efficacious and well tolerated when used in combination with the calcineurin inhibitor Prograf(r) (tacrolimus) and corticosteroids. Presenting the results on behalf of the study group, Professor Yves Vanrenterghem (Department of Nephrology, Universitaire Ziekenhuizen, Leuven, Belgium) revealed that FK778 treated patients showed lower acute rejection rates, especially when patients were under higher drug exposure early on after transplantation. Unlike currently available immunosuppressants, FK778 exerts its immunosuppressive activity at the molecular level via the suppression of de-novo pyrimidine biosynthesis, inhibiting the action of dihydroorotate dehydrogenase, an enzyme critical in the process, and consequently inhibiting cell proliferation. In addition to its immunosuppressive properties, FK778 has also been shown in in-vitro and animal studies to exhibit antiviral activity, inhibiting the virion assembly process of cytomegalovirus (CMV) and polyoma virus. This is important in immunocompromised transplant patients because CMV infection is a common complication after transplantation and for patients affected it is a risk factor for chronic allograft dysfunction. For polyoma virus the effect of FK778 is even more important, because the infection often causes subsequent graft failure. Clinical development of FK778 will continue. Recently a large scale, pan-European, multicentre dose finding Phase IIb study has started. Notes to Editors Acute rejection is mediated by T cells (cellular acute rejection) and by B-cell-derived antibodies (vascular acute rejection), and tends to occur within days to the first few months after organ transplantation. The mechanism behind chronic allograft dysfunction, which occurs months to years after transplantation, has not been fully elucidated, but both cellular and humoral immune responses play a role. Important risk factors for chronic allograft dysfunction include episodes of unresolved acute rejection and an array of non-immunological factors, including CMV infection. Fujisawa GmbH is a subsidiary of Fujisawa Pharmaceutical Co., Ltd., based in Osaka, Japan. Fujisawa Pharmaceutical Co., Ltd. is among the world's top 30 pharmaceutical companies and employs over 8000 people in Japan, Europe, North America and Asia. Since its launch of Prograf(r) in Japan in 1993, the first in the world, Fujisawa has become one of the world's leading transplant and immunosuppression companies. Fujisawa plans to maintain its commitment to transplantation, and is dedicated both to improving the results of solid-organ transplantation and to ensuring the health and quality of life of patients. Prograf(r) is currently available in nearly 70 countries and forms the centrepiece of Fujisawa's continuing growth. Additional information on Fujisawa GmbH can be found on the Company's Web site at www.fujisawaeurope.com. Reference 1. Vanrenterghem Y, van Hooff J, Wlodarczyk Z, Klinger M, Squifflet J and the European FK778-Kidney-Transplant-Study-Group. A multicentre, randomised, double-blind study to evaluate the safety, tolerability, efficacy and pharmacokinetics of malononitrilamide FK778 in combination with tacrolimus and steroid therapy in renal transplantation. Presented at the 11th Congress of the European Society for Organ Transplantation, 20-24 September 2003, Venice, Italy. Abstract 102. Contact: Marité Ode Fujisawa GmbH, Munich, Germany T: +49 89 45442249 F: +49 89 434129 media@fujisawa.de Subscribers please note that material bearing the slug "PROTEXT" is not part of CTK's news service and is not to be published under the "CTK" slug. Protext is a commercial service providing distribution of press releases from clients, who are identified in the text of Protext reports and who bear full responsibility for their contents. PROTEXT