BACKGROUND: Inhalational anthrax caused by Bacillus anthracis is associated with 
high mortality primarily due to toxin-mediated injury. Raxibacumab is a human 
IgG1lambda monoclonal antibody directed against protective antigen, a component 
of the anthrax toxin.
METHODS: We evaluated the efficacy of raxibacumab as a prophylactic agent and 
after disease onset in a total of four randomized, placebo-controlled studies 
conducted in rabbits and monkeys. Animals were exposed to an aerosolized target 
exposure of B. anthracis spores that was approximately 100 times (in the 
prophylactic studies) and 200 times (in the therapeutic-intervention studies) 
the median lethal dose. In the therapeutic-intervention studies, animals were 
monitored for the onset of symptoms. Animals with detectable protective antigen 
in serum, a significant increase in temperature, or both received a single 
intravenous bolus of placebo or raxibacumab at a dose of either 20 mg per 
kilogram of body weight or 40 mg per kilogram. The primary end point was 
survival at day 14 (in rabbits) or at day 28 (in monkeys). Safety studies were 
conducted with intravenous raxibacumab (40 mg per kilogram) in 333 healthy human 
volunteers.
RESULTS: In both rabbits and monkeys, the time to detection of protective 
antigen correlated with the time to bacteremia (r=0.9, P<0.001). In the 
therapeutic-intervention studies, the survival rate was significantly higher 
among rabbits that received raxibacumab at a dose of 40 mg per kilogram (44% [8 
of 18]) than among rabbits that received placebo (0% [0 of 18]; P=0.003). 
Raxibacumab treatment also significantly increased survival in monkeys (64% [9 
of 14], vs. 0% [0 of 12] with placebo; P<0.001). In human subjects, intravenous 
raxibacumab at a dose of 40 mg per kilogram had a half-life of 20 to 22 days and 
provided a maximum concentration of the drug in excess of levels that are 
protective in animals. Concentrations of raxibacumab provide a surrogate end 
point that should be predictive of clinical benefit.
CONCLUSIONS: A single dose of raxibacumab improved survival in rabbits and 
monkeys with symptomatic inhalational anthrax. (ClinicalTrials.gov number, 
NCT00639678.)