AAC Accepts, published online ahead of print on 17 February 2009

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Antimicrob. Agents Chemother. doi:10.1128/AAC.01596-08
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

ST-246® Antiviral Efficacy in a Non-Human Primate Monkeypox Model: Determination of the Minimal Effective Dose and Human Dose Justification

Robert Jordan, Arthur Goff, Annie Frimm, Michael L. Corrado, Lisa E. Hensley, Chelsea M. Byrd, Eric Mucker, Josh Shamblin, Tove' C. Bolken, Carly Wlazlowski, Wendy Johnson, Jennifer Chapman, Nancy Twenhafel, Shanthakumar Tyavanagimatt, Adams Amantana, Jarasvech Chinsangaram, Dennis E. Hruby^*, and John Huggins

SIGA Technologies, Corvallis, OR; US Army Medical Research Institute of Infectious Diseases, Frederick, MD; INC Research, Raleigh, NC

^* To whom correspondence should be addressed. Email: dhruby{at}siga.com.

Therapeutics are being sought to treat pathogenic orthopoxvirus infections. In the absence of patients with disease, animal models of orthopoxvirus disease are essential for evaluating the efficacy of antiviral drugs, and establishing the appropriate dose and duration of human therapy. Infection of non-human primates (NHP) via intravenous injection (IV) of monkeypox virus has been used to evaluate a promising therapeutic drug candidate, ST-246. ST-246 administered at 3 days post-infection (dpi), which corresponds to the secondary viremia stage of disease, at four different doses, from 100 mg/kg down to 3 mg/kg, once a day for 14 days, was able to protect NHP 100% from a lethal infection with monkeypox virus (MPX) and reduce the viral load and lesion formation. In NHP, a ST-246 dose of 10 mg/kg/day for 14 days resulted in blood exposure comparable to levels attained in humans administered 400 mg in the fed state. These results suggest that a once daily oral dosage of 400 mg for 14 days will be effective to prevent or treat smallpox or monkeypox infections in man.

This article has been cited by other articles:

• Berhanu, A., King, D. S., Mosier, S., Jordan, R., Jones, K. F., Hruby, D. E., Grosenbach, D. W. (2009). ST-246 Inhibits In Vivo Poxvirus Dissemination, Virus Shedding, and Systemic Disease Manifestation. Antimicrob. Agents Chemother. 53: 4999-5009 [Abstract] [Full Text]