Raxibacumab

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Compound Name:RaxibacumabMolecular Target:Anthrax toxinMolecular Structure:Human IgG1-lambda mABLicensed Indication:inhalation anthraxManufacturer and/or Distributor:Human Genome Sciences/ GlaxoSmithKlineInitial FDA Approval:2012Summary:Raxibacumab is a fully human IgG1-lambda monoclonal antibody that recognizes the protective antigen (PA) portion of the toxin produced by Bacillus anthracis and prevents the toxin from entering cells and killing them. It is approved for treatment of inhalation anthrax in adults and children, along with appropriate antibiotics, or for prophylaxis of inhalation anthrax when there are no better alternatives. It was approved by the FDA through the “Animal Efficacy Rule” on the basis of demonstration of efficacy in rabbits and monkeys, the potential for substantial health benefit for humans, and lack of toxicity in human volunteers. Thus, there is no direct demonstration of efficacy in humans, clearly because controlled trials would be ethically impossible. The recommended adult dosage of raxibacumab is a single dose of 40 mg/kg given intravenously over a period of two hours and 15 minutes. The recommended dose for children is based on weight.    As a single agent given at the time of challenge with 100x the lethal dose of anthrax spores, raxibacumab at the highest dose tested (40mg/kg) was 90-100% effective in preventing mortality in the animal studies. When given at the time bacteremia was detected (~1-2 days) after exposure to 200x the lethal dose it was about 50% effective in preventing mortality. It also improved survival when given along with levofloxacin 84 hours after exposure. Raxibacumab can only be obtained from the CDC. It is given as a single IV dose.   The main adverse events seen in >800 human volunteers were mild to moderate infusion reactions.References

Package Insert: http://us.gsk.com/products/assets/us_raxibacumab.pdf

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2. Migone T-S, Subramanian G, Zhong J, Healey L, Corey A, Devalaraja M, et al. Raxibacumab for the treatment of inhalational anthrax. N Engl J Med. 2009 Jul 9;361(2):135-44. http://www.ncbi.nlm.nih.gov/pubmed/19587338

3. Goldenberg M. Pharmaceutical approval update. P & T: a peer-reviewed journal for formulary management. 2013;38(2):86-95.  http://www.ncbi.nlm.nih.gov/pubmed/23599674 

4. Migone TS, Bolmer S, Zhong J, Corey A, Vasconcelos D, Buccellato M, Meister G. Added Benefit of Raxibacumab to Antibiotic Treatment of Inhalational Anthrax. Antimicrob Agents Chemother. 2014 Dec 8. http://www.ncbi.nlm.nih.gov/pubmed/25487792

5. Kummerfeldt CE. Raxibacumab: potential role in the treatment of inhalational anthrax. Infect Drug Resist. 2014 Apr 29;7:101-9. http://www.ncbi.nlm.nih.gov/pubmed/24812521

6. Tsai CW, Morris S. Approval of Raxibacumab for the Treatment of Inhalation Anthrax Under the US Food and Drug Administration "Animal Rule". Front Microbiol. 2015 Dec 1;6:1320. http://www.ncbi.nlm.nih.gov/pubmed/26648915

7. Huang E, Pillai SK, Bower WA, Hendricks KA, Guarnizo JT et al. Antitoxin Treatment of Inhalation Anthrax: A Systematic Review. Health Secur. 2015 Nov-Dec;13(6):365-77. https://www.ncbi.nlm.nih.gov/pubmed/26690378

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