Shares of SIGA Technologies Inc. jumped 130 percent on news that its smallpox drug, SIGA-246, demonstrated 100 percent protection against the human smallpox virus in a primate trial.
Results showed that the drug prevented symptoms of the disease when administered to cynomolgus monkeys either simultaneously or following exposure to the virus. That suggests that the antiviral could be used as both a prophylactic and a therapeutic against smallpox, which is considered by the Centers for Disease Control and Prevention to be one of the biggest biowarfare threats.
"It's a Category A agent, for which there is no drug available," said Dennis Hruby, chief scientific officer of New York-based SIGA, adding that if the variola virus that causes smallpox were introduced into the population, "virtually everybody would get the disease, and 30 percent to 40 percent of people would die."
Though there is a smallpox vaccine, it's effective only if administered within a few days of exposure to the virus and can lead to dangerous complications for some people, particularly those who are immunocompromised.
There have been no natural occurrences of smallpox since the late 1970s, so human testing of SIGA-246 is limited to safety studies to determine any adverse reactions and to make sure there are adequate levels of the drug in subjects' bloodstreams. The proof-of-concept data will come from mouse and primate animal models.
"So the fact that we've been able to [show efficacy] in primates is a big milestone for the program," Hruby told BioWorld Today.
Wall Street agreed, as the company's shares (NASDAQ:SIGA) gained $2.57 Wednesday to close at $4.54.
The primate study, conducted in a lab at the CDC in Atlanta, involved three groups: a placebo-control group and two groups receiving SIGA-246, either at the same time as intravenous high dosing with the smallpox virus or one day after infection. The drug was given orally, once a day, and Hruby said that "is how we anticipate administering the drug to humans - as a tablet or capsule once a day."
Data showed that SIGA-246 completely prevented lesion formation and decreased viral loads, with no apparent toxicity.
The drug is designed to inhibit cysteine proteinase, a viral protein needed to spread the virus from an infected cell into the bloodstream. Early evidence indicated that the presence of SIGA-246 not only prevents the infection from spreading, but also helps induce a protective immune response at the same time, Hruby said.
"And we've shown in animals that we can give them the drug before we expose them, at the time we expose them or after we expose them to the virus and protect them," he said, adding that the virus progresses slowly enough in humans - it's about 10 to 12 days from exposure before the first symptoms and then a couple of weeks before late-stage disease - which offers "quite a therapeutic window."
SIGA already completed a single-dose safety trial in humans, with no adverse events reported, and is gearing up for a multidose human trial, expected to start in early 2007. The company also has to complete toxicology work and its animal efficacy studies before filing a new drug application, anticipated sometime in 2009, Hruby said, though much of the timing depends on government contracts and approvals.
To date, SIGA has received about $27 million in funding to support development of SIGA-246, including a $16.5 million grant awarded earlier this month by the National Institute of Allergy and Infections Disease, part of the National Institutes of Health in Bethesda, Md. That award was announced the same day the company terminated its previously announced plans to merge with Annapolis, Md.-based PharmAthene Inc. (See BioWorld Today, Oct. 6, 2006.)
Right now the need for a smallpox drug comes from the biodefense space, meaning the U.S. government likely would be the biggest customer for SIGA-246 under Project Bioshield, but Hruby said SIGA's product could have other ramifications.
"There are naturally occurring viruses that could come into our environment," he said, "and it would be nice to have drugs to prevent those diseases."
SIGA has antiviral programs targeting other Category A pathogens in preclinical development, including a program targeting Lassa fever, which is caused by an arenavirus, and Ebola, which stems from a filovirus.