Human Monoclonal Antibody against Endotoxin

Abstract

Little progress has been made over the past several years in the treatment of gram-negative bacteremia and septic shock. Advances in biotechnology have led to the development of human monoclonal antibody against endotoxin (HA-1A), a toxic mediator of the septic response. HA-1A is an immunoglobulin M antibody to the lipid A component of the endotoxin molecule. It distributes into an apparent volume of distribution 10–20 percent larger than plasma volume and has a circulating half-life of 16.0 hours. In a major, multicenter, double-blind trial of HA-1A 100 mg administered intravenously versus placebo, mortality was greatly reduced in HA-1A recipients with gram-negative bacteremia. Increased survival was noted early and was sustained throughout the 28-day study period in patients with and without shock at the time of enrollment. HA-1A has an excellent safety profile; thus far only two minor hypersensitivity reactions and no drug interactions have been reported. Based on currently available information, the release of HA-1A as adjunct therapy for patients with gram-negative bacteremia with or without shock represents a significant therapeutic advance. Investigations are underway to define the optimal dose of HA-1A and its duration of action. Comparative trials between HA-1A and competitive products are necessary.