Officials of the US Food and Drug Administration (FDA) in mid-December approved ABthrax, or raxibacumab, for use in patients with inhalational anthrax. This approval is the first under the agency's 'animal rule', established for evaluating the efficacy of products that would be unethical or impossible to test (except for safety) in humans. ABthrax is a human monoclonal antibody (mAb), licensed for use as an adjunct to conventional antibiotics such as Cipro (ciprofloxacin).

Bacillus anthracis is the causative agent of anthrax, which affects both humans and animals. Credit: Eye of Science / Photo Researchers, Inc

This is also the first time FDA approved a mAb for an antibacterial indication, according to Steven Projan, a senior vice president at MedImmune in Gaithersburg, Maryland. “This should signal a new era in pathogen-specific drugs for the prevention and/or treatment of bacterial infections for bacteria like Staphylococcus aureus and Pseudomonas aeruginosa, where there are already monoclonal antibodies in clinical trials,” he says.

ABthrax interferes with the binding of a key antigen of Bacillus anthracis, the bacterial pathogen responsible for anthrax—a potentially deadly infection, particularly when it involves the lungs and becomes systemic. Spores of this pathogen can be used as a bioterror agent—in 2001, spores deliberately distributed through the US Postal Service led to 5 deaths amid 17 cases of anthrax—or in biological warfare. The mAb was developed by Rockville, Maryland–based Human Genome Sciences, a biotech company that GlaxoSmithKline of London acquired last August (Nat. Biotechnol. 30, 815, 2012).

Under a contract from 2005, FDA allowed the US Department of Health and Human Services to purchase and stockpile ABthrax under Project BioShield and within its Biomedical Advanced Research and Development Authority (BARDA). Until full approval came in 2012, however, the mAb was subject to FDA emergency use authority (EUA), according to Amesh Adalja, senior associate at the Center for Biosecurity, a nonprofit organization of the University of Pittsburgh Medical School, in Baltimore. “FDA approval [of ABthrax] makes it easier for physicians to use the product,” he says.

Whether the agency will eventually approve ABthrax to use independently for post-exposure prophylaxis—in which case it would compete head-to-head with Cipro or other antibiotics—is a matter of speculation. Although considerably more expensive than the antibiotic, the injected mAb has a significantly longer half-life than the antibiotic, according to Adalja. That trait could make it easier to use and could overcome poor compliance from some patients who balk at taking the antibiotic for 60 days following exposure, he says.

The BARDA stockpile also includes a vaccine to protect against infection by B. anthracis and an anthrax immune globulin, a polyclonal mixture, produced by Cangene of Winnipeg in Manitoba, Canada, that, like ABthrax, can be used to help treat cases of inhalational anthrax. Neither of these products is fully licensed yet, according to Robin Robinson, director of BARDA, who says they may move toward that goal in 2014. “We want them to be licensed, and it would lead to their better acceptance by the public if there were an emergency,” he says. Moreover, having ABthrax approved under the FDA animal rule through testing in rabbits and nonhuman primates is an important “first” as well as a “milestone in overall preparedness,” meeting some of the goals laid out in the Project BioShield Act of 2004.

Natural cases of anthrax appear only rarely in the US but more frequently in Bangladesh and other countries where sheep or other animal hides are collected. Moreover, during the past several years, parts of Europe reported small outbreaks of injectable anthrax among heroin users. However, because of its relatively high cost compared to conventional antibiotics, ABthrax's main sales are likely to remain through government purchases for stockpiling, according to both Robinson and Adalja. “Nothing in our contracts prevents them purchasing [ABthrax or comparable products],” Robinson says. “The more countries, the better, so the US is not the only one supporting these efforts.”