FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 361:135-144 July 9, 2009 Number 2 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Supplementary Material Purchase this article Editorial by Nabel, G. J. Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

ABSTRACT

Background Inhalational anthrax caused by Bacillus anthracis is associated with high mortality primarily due to toxin-mediated injury. Raxibacumab is a human IgG1 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 [ClinicalTrials.gov] .)

Source Information

From Human Genome Sciences, Rockville, MD (T.-S.M., G.M.S., J. Zhong, L.M.H., A. Corey, M.D., L.L., S.U., J. Zimmerman, A. Chen, M.L., S.D.B.); and Battelle Biomedical Research Center, Columbus, OH (G.M., K.G., D.S., J.M.).

Address reprint requests to Dr. Migone or Dr. Subramanian at Human Genome Sciences, 14200 Shady Grove Rd., Rockville, MD 20850, or at thi_migone{at}hgsi.com or mani_subramanian{at}hgsi.com.

Full Text of this Article

This article has been cited by other articles:

• Nabel, G. J. (2009). Protecting against Future Shock -- Inhalational Anthrax. NEJM 361: 191-193 [Full Text]  
• (2009). A Monoclonal Antibody for Preventing and Treating Inhalational Anthrax. JWatch Infect. Diseases 2009: 1-1 [Full Text]