Reparixin, joint development of SaterRX LLC and Dompe s.p.a., is in pilot Phase II clinical trial for prevention of early allograft dysfunction in patients after orthotopic liver allotransplantation (OLAT).
Formerly referred to as repertaxin, this molecule is a first-in-class potent low molecular weight blocker of CXCL8 biological activity. Reparixin is a non-competitive allosteric inhibitor of the CXCL8 receptors CXCR1 and CXCR2. Interaction of Reparixin with CXCL8 receptors inhibits the intracellular signal transduction events activated by binding of CXCL8 to CXCR1 and CXCR2.
Results show that Reparixin is in vitro a potent and specific inhibitor of CXCL8 induced recruitment of human (polymorphonuclear) PMN. Moreover, Reparixin reduces both PMN recruitment and tissue damage in animal models of warm and cold Ischemia/Reperfusion (I/R).
CXCL8 role has been claimed in a variety of inflammatory conditions. Therefore the modulation or inhibition of CXCL8 activity is considered as a valid target for the development of innovative treatments of a variety of severe clinical conditions, still with an unmet medical need.
Reparixin received orphan drug designation for the “prevention of delayed graft function after (solid) organ transplantations” by the European Commission of Orphan Medicinal Products in September 2001 and by the Food and Drug Administration in January 2003.
During non-clinical development Reparixin prevents PMN infiltration and tissue damage in animal models of ischemia/reperfusion in fatty liver.
Compound is developing for continuous intravenous infusion and now entering in Phase 2 clinical trial to evaluate its efficacy and safety in preventing EAD in patients after orthotopic liver allotransplantation (OLAT). It is expected to reduce incidens of EAD in patients after liver transplantation in comparison with patients receiving standard immunosuppressive therapy.