Evaluation of intravenous anthrax immune globulin for treatment of inhalation
anthrax.
Author(s): Mytle N(1), Hopkins RJ, Malkevich NV, Basu S, Meister GT, Sanford DC, Comer JE,
Van Zandt KE, Al-Ibrahim M, Kramer WG, Howard C, Daczkowski N, Chakrabarti AC,
Ionin B, Nabors GS, Skiadopoulos MH.
Affiliation(s): Author information:
(1)Emergent BioSolutions Inc., Gaithersburg, Maryland, USA.
Publication date & source: 2013, Antimicrob Agents Chemother. , 57(11):5684-92
Bacillus anthracis toxins can be neutralized by antibodies against protective
antigen (PA), a component of anthrax toxins. Anthrivig (human anthrax
immunoglobulin), also known as AIGIV, derived from plasma of humans immunized
with BioThrax (anthrax vaccine adsorbed), is under development for the treatment
of toxemia following exposure to anthrax spores. The pharmacokinetics (PK) of
AIGIV was assessed in naive animals and healthy human volunteers, and the
efficacy of AIGIV was assessed in animals exposed via inhalation to aerosolized
B. anthracis spores. In the clinical study, safety, tolerability, and PK were
evaluated in three dose cohorts (3.5, 7.1, and 14.2 mg/kg of body weight of
anti-PA IgG) with 30 volunteers per cohort. The elimination half-life of AIGIV in
rabbits, nonhuman primates (NHPs), and humans following intravenous infusion was
estimated to be approximately 4, 12, and 24 days, respectively, and dose
proportionality was observed. In a time-based treatment study, AIGIV protected 89
to 100% of animals when administered 12 h postexposure; however, a lower survival
rate of 39% was observed when animals were treated 24 h postexposure,
underscoring the need for early intervention. In a separate set of studies,
animals were treated on an individual basis upon detection of a clinical sign or
biomarker of disease, namely, a significant increase in body temperature (SIBT)
in rabbits and presence of PA in the serum of NHPs. In these trigger-based
intervention studies, AIGIV induced up to 75% survival in rabbits depending on
the dose and severity of toxemia at the time of treatment. In NHPs, up to 33%
survival was observed in AIGIV-treated animals. (The clinical study has been
registered at ClinicalTrials.gov under registration no. NCT00845650.).
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