New Drugs and Devices From 2011 – 2012 That Might Change Your Practice

Joe Lex, MD

Disclosures

Western J Emerg Med. 2013;14(6):619-628. 

In This Article

Abthrax® (Raxibacumab)

Raxibacumab is a newly approved drug for treatment of inhalational anthrax. It has the lumbering chemical formula C6320H9794N1702O1998S42. Like all monoclonal antibodies, the source and purpose are in the name. The last syllable (-mab) tells you that it is a monoclonal antibody. The antepenultimate syllable (-u-) tells you the source of the DNA is human (mouse DNA is designated by -o- and chimeric DNA by -xu-). And the preceding syllable (-bac-) tells you that it is an antibacterial agent.

Unlike antibiotics, which eradicate the Bacillus anthracis bacterium itself, raxibacumab targets the toxins produced by B. anthracis. These toxins are the cause of death in most human inhalational anthrax disease cases, including those in the 2001 attacks. As you may recall, as many as 68 victims were infected with inhalational anthrax delivered through the U.S. postal system, and 5 of them died despite aggressive antibiotic therapy.

More than 20,000 doses of raxibacumab have been in the Strategic National Stockpile since 2009. The stockpile includes other vaccines, antibiotics, and antitoxins that target anthrax and other agents of biological, nuclear and chemical warfare. Like raxibacumab, not all of these products are licensed.

Because naturally occurring inhalational anthrax infection in humans is rare (and studies deliberately exposing humans to the pathogen would be unethical), efficacy studies of raxibacumab were conducted in animals under the FDA's Animal Rule. It is the first monoclonal antibody approved under this rule. Established in 2002, the Animal Rule allows developers to seek approval for the marketing of drugs or biologics based on efficacy data from animal studies, provided certain criteria are met. Safety data can be collected from humans, however, as was done with raxibacumab. Raxibacumab is administered in a single 40 mg/kg dose delivered intravenously over 2.25 hours. The instructions recommend premedication with diphenhydramine 1 hour before infusion.

Dividing anthrax bacilli produces protective antigen (PA), lethal factor (LF) and edema factor (EF). PA facilitates binding of LF and EF to anthrax toxin receptor (ATR) on mammalian cell surfaces, resulting in a protein-receptor complex that enables LF and EF to enter cells. These toxins inhibit normal immune system functioning, interfere with signal transduction pathways, and ultimately cause cell death. Antibiotics help control the bacterial infection, but they fail to clear toxins from the bloodstream. Vaccines can be effective over time, but they are slow acting initially and require booster doses to maintain immunity. By binding protective antigens, raxibacumab prevents LF and EF from entering cells, preventing progression of the disease.

Raxibacumab-treated animals had improved survival over control in 2 relevant animal models both in combination with antibiotics and alone. It is strictly for treating inhalational symptoms: Raxibacumab does not cross the blood-brain barrier and does not prevent or treat meningitis. Whether the drug will be dispensed solely by the U.S. government is unclear. I cannot find a charge for individual doses, but medicines supplied by the Strategic National Stockpile are free.

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....