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Link to original content: https://pubmed.ncbi.nlm.nih.gov/36251555/
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. 2022 Oct 17;75(Suppl 3):S441-S450.
doi: 10.1093/cid/ciac593.

Pre- and Postlicensure Animal Efficacy Studies Comparing Anthrax Antitoxins

Raymond M Slay  1 , Rachel Cook  2 , Katherine Hendricks  3 , David Boucher  4 , Michael Merchlinsky  4
Affiliations

Pre- and Postlicensure Animal Efficacy Studies Comparing Anthrax Antitoxins

Raymond M Slay et al. Clin Infect Dis. .

Abstract

Background: The deliberate use of Bacillus anthracis spores is believed by the US government to be a high bioweapons threat. The first line of defense following potential exposure to B. anthracis spores would be postexposure prophylaxis with antimicrobials that have activity against B. anthracis. Additional therapies to address the effects of toxins may be needed in systemically ill individuals. Over the last 2 decades, the United States government (USG) collaborated with the private sector to develop, test, and stockpile 3 antitoxins: anthrax immunoglobulin intravenous (AIGIV), raxibacumab, and obiltoxaximab. All 3 products target protective antigen, a protein factor common to the 2 exotoxins released by B. anthracis, and hamper or block the toxins' effects and prevent or reduce pathogenesis. These antitoxins were approved for licensure by the United States Food and Drug Administration based on animal efficacy studies compared to placebo.

Methods: We describe USG-sponsored pre- and postlicensure studies that compared efficacy of 3 antitoxins in a New Zealand White rabbit model of inhalation anthrax; survival following a lethal aerosolized dose of B. anthracis spores was the key measure of effectiveness. To model therapeutic intervention, intravenous treatments were started following onset of antigenemia.

Results: In pre- and postlicensure studies, all 3 antitoxins were superior to placebo; in the postlicensure study, raxibacumab and obiltoxaximab were superior to AIGIV, but neither was superior to the other.

Conclusions: These data illustrate the relative therapeutic benefit of the 3 antitoxins and provide a rationale to prioritize their deployment.

Keywords: Bacillus anthracis; Inhalation anthrax; New Zealand white rabbit; antitoxin; protective antigen.

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Figures

Figure 1.
Figure 1.
Kaplan–Meier curve representing time-to-death and survival data for raxibacumab against inhalation anthrax in rabbits.
Figure 2.
Figure 2.
Kaplan–Meier curve representing time-to-death and survival data for obiltoxaximab against inhalation anthrax in rabbits. Abbreviation: UTMB, University of Texas Medical Branch.
Figure 3.
Figure 3.
Kaplan–Meier curve representing time-to-death and survival data by group for all animals. Abbreviation: AIGIV, anthrax immunoglobulin intravenous.
See this image and copyright information in PMC

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