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
attacks.
Daniel R. Lucey, MD, MPH
Director, Center
for Biologic Counterterrorism and Emerging Diseases
EROne
Institutes,
Adjunct
Professor of Microbiology and Immunology,
Website: www.BePast.org e-mail: Daniel.R.Lucey@Medstar.net