SIGA Technologies is a commercial-stage pharmaceutical company focused on the health security market. SIGA is based in New York and partnered with Meridian Medical Technologies, a subsidiary of Pfizer. Health security includes countermeasures for biological, chemical, radiological, and nuclear attacks, as well as vaccines and therapies for emerging infectious diseases and health preparedness. SIGA receives funding and technical support from the Biomedical Advanced Research and Development Authority (BARDA) under the Assistant Secretary for Preparedness and Response (ASPR), within the U.S. Department of Health and Human Services (HHS), under ongoing USG Contract No. 75A50118C00019 (19C).
SIGA Technologies produces the smallpox antiviral drug TROPXX (tecovirimat; ST-246), which is an oral formulation approved in the US, Canada, and Europe. The oral version of TROPXX was approved in 2018 in the US and sold to governments for stockpiling in case of a smallpox outbreak. In Europe, TROPXX is also approved to treat monkeypox, cowpox, and complications from immunization with vaccinia. On May 19, 2022, SIGA Technologies received US approval for the intravenous (IV) formulation of the drug TPOXX. The IV version of TROPXX can be used in patients whose throats are damaged by smallpox and cannot swallow the oral formulation. Competitor companies producing the smallpox vaccine include Emergent BioSolutions and Barvarian Nordic.
Although smallpox was eradicated in the 1980s, the continued existence of samples of the smallpox virus in research laboratories has led to concerns that it could be used in biological warfare. The current vaccine for smallpox has a risk of side effects that is too high to justify routine vaccination when there is a low risk of smallpox virus exposure.
Tecovirimat was identified in a high-throughput screen in 2005 as a small molecule that targets the viral structural protein called F13 homolog, alias p37. The F13 homolog protein has a crucial role in the process the virus uses to become wrapped in membranes. Tecovirimat was shown to be effective in preventing the replication of the cowpox virus, a virus related to smallpox. The drug was shown to disrupt the interaction between F13 and two cellular proteins, Rab9 and TIP47, which are involved in membrane trafficking. Membrane trafficking is the process using membrane-bound vesicles by which proteins and other macromolecules are moved throughout the cells, taken into cells, or released from cells.
Tecovirimat was reported to be safe for healthy humans to ingest, but it cannot be tested on humans with smallpox as there are none. The drug was reported to prevent death in rabbits and monkeys infected with a lethal dose of rabbitpox or monkeypox. The drug was used in 2007 on an emergency basis to successfully treat a two-year-old boy who was infected and critically ill with vaccinia virus infection through exposure to his father, a military member who had received the smallpox vaccine.
SIGA does not have a manufacturing infrastructure. Contract manufacturing organizations (CMOs) are used to procure commercial raw materials and supplies to manufacture TPOXX. The four main CMOs that manufacture TROXX are W.R. Grace and Company, Powdersize, LLD, Catalent Pharma Solutions LLC, and Packaging Coordinators, LLC.
Oral Tecovirimat for the Treatment of Smallpox
Douglas W. Grosenbach, Kady Honeychurch, Eric A. Rose, Jarasvech Chinsangaram, Annie Frimm, Biswajit Maiti, Candace Lovejoy, Ingrid Meara, Paul Long, Dennis E. Hruby
July 5, 2018
The mechanism of the monkeypox antiviral