Spring 2007
NIAID Discovery News
Steps Towards a Smallpox Treatment
Through the middle of the 20th century, smallpox was a disease that annually afflicted tens of millions of people around the world, killing as many as 30 percent and leaving many others with permanent blindness and disfiguring scars. But thanks to the World Health Organization’s highly successful smallpox eradication program in the 1960s and 1970s, the world has been free from smallpox. The last naturally occurring case was in October 1977, and except for a few known samples in laboratory freezers, variola, the virus that causes smallpox, no longer exists.
The anthrax attacks in fall 2001, however, raised the possibility that variola might re-emerge as an agent of bioterrorism if unaccounted for samples of the virus fell into the wrong hands. While the old smallpox vaccine could be resurrected to help prevent the virus’ spread, there are no approved antiviral drugs for treating variola infections.
In September 2006, the National Institute of Allergy and Infectious Diseases (NIAID) awarded a contract to SIGA Technologies Inc., headquartered in New York City, to develop and clinically test its anti-variola compound, ST-246.
“Poxviruses are unique in that they make two forms of their virion [infectious particle],” explains Dennis E. Hruby Ph.D., Chief Scientific Officer of SIGA. The initial form of the virus produced within a cell must mature into a second form in order to be transmissible. ST-246 targets the protein that catalyzes this conversion, says Dr. Hruby, and prevents it from functioning properly. In theory, this should halt the spread of the virus within a person’s body and improve an individual’s prognosis, especially if given early in the course of an infection.
The compound has received an orphan drug designation from the U.S. Food and Drug Administration (FDA), which may help ST-246 to be approved in the United States. The FDA also awarded the compound fast-track status, which will expedite its regulatory review.
Clinical trials of the compound are already under way, thanks in part to several awards in the last few years from NIAID to SIGA to fund the product’s preclinical development. Last year, the company successfully conducted the initial human safety trial, and NIAID-funded clinical trials are now taking place to determine safe dosing levels for ST-246. In parallel, the compound is undergoing NIAID-funded pivotal animal efficacy trials, as part of the licensure path under the FDA’s “animal rule,” which allows efficacy trials in relevant animals to be substituted for human efficacy trials. Following successful human safety trials along with data from the pivotal animal efficacy trials, the compound will then be ready for FDA review for approval.
If all goes well, says Dr. Hruby, SIGA hopes to submit a new drug application to the FDA sometime in 2009.
—Jason Socrates Bardi
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