title: Development of the small-molecule antiviral ST-246 as a smallpox therapeutic.
abstract: Naturally occurring smallpox has been eradicated, yet it remains as one of the highest priority pathogens due to its potential as a biological weapon. The majority of the US population would be vulnerable in a smallpox outbreak. SIGA Technologies, Inc. has responded to the call of the US government to develop and supply to the Strategic National Stockpile a smallpox antiviral to be deployed in the event of a smallpox outbreak. ST-246(®) (tecovirimat) was initially identified via a high-throughput screen in 2002, and in the ensuing years, our drug-development activities have spanned in vitro analysis, preclinical safety, pharmacokinetics and efficacy testing (all according to the 'animal rule'). Additionally, SIGA has conducted Phase I and II clinical trials to evaluate the safety, tolerability and pharmacokinetics of ST-246, bringing us to our current late stage of clinical development. This article reviews the need for a smallpox therapeutic and our experience in developing ST-246, and provides perspective on the role of a smallpox antiviral during a smallpox public health emergency.
authors.affiliation: SIGA Technologies, Inc., 4575 SW Research Way, Suite 230, Corvallis, OR 97333, USA.
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Grosenbach
authors.forename: Robert
authors.initials: R
authors.lastname: Jordan
authors.forename: Dennis E
authors.initials: DE
authors.lastname: Hruby