Inhalational
anthrax has high mortality even with
antibiotic treatment, and
antitoxins are now recommended as an adjunct to standard antimicrobial regimens. The efficacy of
obiltoxaximab, a
monoclonal antibody against
anthrax protective antigen (PA), was examined in multiple studies conducted in two animal models of inhalational
anthrax. A single intravenous bolus of 1 to 32 mg/kg of
body weight obiltoxaximab or placebo was administered to New Zealand White rabbits (two studies) and cynomolgus macaques (4 studies) at disease onset (significant body temperature increase or detection of serum PA) following lethal challenge with aerosolized Bacillus anthracis spores. The primary endpoint was survival. The relationship between efficacy and disease severity, defined by pretreatment
bacteremia and
toxemia levels, was explored. In rabbits, single doses of 1 to 16 mg/kg
obiltoxaximab led to 17 to 93% survival. In two studies, survival following 16 mg/kg
obiltoxaximab was 93% and 62% compared to 0% and 0% for placebo (P = 0.0010 and P = 0.0013, respectively). Across four macaque studies, survival was 6.3% to 78.6% following 4 to 32 mg/kg
obiltoxaximab. In two macaque studies, 16 mg/kg
obiltoxaximab reduced
toxemia and led to survival rates of 31%, 35%, and 47% versus 0%, 0%, and 6.3% with placebo (P = 0.0085, P = 0.0053, P = 0.0068). Pretreatment
bacteremia and
toxemia levels inversely correlated with survival. Overall,
obiltoxaximab monotherapy neutralized PA and increased survival across the range of disease severity, indicating clinical benefit of toxin neutralization with
obiltoxaximab in both early and late stages of inhalational
anthrax.