Anthrax Antitoxin Antibody: Second Source to be Added to US Stockpile
On 28 July 2006 the U.S. Department of Health and Human Services (HSS) announced a contract with a Canadian company, Cangene Corporation, for 10,000 courses of therapy with anthrax antitoxin antibody, termed “Anthrax Immune Globulin (AIG)”. Delivery to the U.S. Strategic National Stockpile (SNS) will begin in 2007. A full description of the HHS press release describing agreement can be found on the HHS website at: http://www.hhs.gov/news/press/2006pres/20060728.html
Once in the stockpile the anthrax immune globulin (AIG) could be used to treat patients, under specific conditions, even prior to the Food and Drug Administration (FDA) licensure for marketing. Such specific regulatory conditions could include the FDA’s Emergency Use Authorization (EUA) or Investigational New Drug (IND) protocols. Of note, however, full payment to Cangene is contingent on AIG receiving FDA approval for marketing. AIG is a hyperimmune product prepared by purification of blood plasma.
Last month, on June 20, HHS announced a contract with Human Genome Sciences, for 20,000 treatment courses of a different anthrax antitoxin, the monoclonal antibody termed “ABthrax”. Delivery to the SNS is anticipated to begin in 2009. As with AIG, full payment is contingent on gaining approval from the FDA for licensure to market this product. A full description of the HHS press release can be found at: http://www.hhs.gov/news/press/2006pres/20060620.html
Antibiotics remain the initial countermeasure against anthrax. In the event of an aerosol attack with anthrax (e.g., as one scenario in the Cities Readiness Initiative (CRI), the CDC has recommended for prophylaxis of exposed persons (but not for those with active disease) since September 2004 adding three doses over one month of post-exposure anthrax vaccination (under an FDA IND). A preventive immune response requires weeks to acquire via this post-exposure “active immunization”.
The stockpiling of two types of an anthrax antitoxin, one plasma derived and the other a monoclonal antibody, will hopefully provide clinicians with yet another countermeasure for the actual treatment of inhalational anthrax, a disease that is now usually fatal if not treated with appropriate antibiotics in the “early-prodromal” or “intermediate-progressive” stages.
Treatment with antibiotics alone during the third and final stage of inhalational anthrax, the “late-fulminant” stage, when anthrax toxin levels are likely at their highest, was not successful during the anthrax attacks in 2001. It should not be assumed, however, that either of the above anthrax toxin inhibitors (AIG or ABthrax) will be highly effective at preventing death in patients with advanced inhalational anthrax. The design of animal experiments to test this hypothesis should be examined closely. Timing is likely to be crucial. Exactly when the antitoxin is given during the three-stage course of inhalational anthrax, and whether the bacteria is susceptible to readily available antibiotics, might be major determinants of how helpful these anthrax antitoxins are to patients.
With Multi-Drug Resistant (MDR) anthrax, such “passive immunization” with anthrax antitoxins such as ABthrax and AIG, should provide at least some significant degree of immediate neutralization of toxin, buying critical time to find some uncommon or still investigational antibiotic(s) to be added as treatment to kill the anthrax toxin-producing bacteria.
One should anticipate that
the next anthrax attack (s) will be with a strain of the Bacillus anthracis bacteria that is resistant to one or more of the
antibiotics that were used as prophylaxis and therapy after the 2001
Daniel R. Lucey, MD, MPH
Director, Center for Biologic Counterterrorism and Emerging Diseases
Professor of Microbiology and Immunology,
Website: www.BePast.org e-mail: Daniel.R.Lucey@Medstar.net