Four years after Siga Technologies (Nasdaq: SIGA) gained approval for a smallpox drug, the Corvallis company is gearing up to get the same antiviral into a clinical trial for monkeypox.
Tpoxx, also known as tecovirimat, is the only drug available to treat the virus, though it is not yet approved in the U.S. for the disease. The Food and Drug Administration designated Tpoxx as an investigational drug for monkeypox, allowing it to be released from the Strategic National Stockpile only after prescribers jump through considerable hoops.
About 15,000 doses have been released from the 1.7 million in the stockpile since the outbreak began. The European Union has already approved Tpoxx to treat monkeypox, and the U.K. approved it in compassionate use cases.
“We’re assisting foreign governments and our own government in getting the drug out to as many people as possible,” said Dennis Hruby, Siga's chief scientific officer, who is a retired professor of microbiology at Oregon State University. “It would appear the drug is having a positive effect in shortening the duration and decreasing the severity of symptoms for monkeypox.”
While the drug's safety was established in 11 clinical trials for smallpox, it must undergo a placebo-controlled trial to determine its efficacy in shortening the symptoms of monkeypox. Siga has been working with groups around the world that are starting these late-stage clinical trials. One will soon begin in the U.S. through the National Institutes of Health’s trial network, Hruby said.
He expects data to be generated in the coming months that will allow the company to apply for full approval, essentially a label expansion or new indication.
There is scant data yet on the drug’s efficacy in humans, other than favorable media reports, but earlier studies showed that it inhibited further lesions in monkeys with advanced disease, Hruby said.
“The primate model is close to the human situation,” he said. “We anticipate similar results in humans.”
Siga also is collaborating with the National Institute of Allergy and Infectious Diseases (NIAID) and Oxford University to treat monkeypox patients in the Central African Republic and is working to launch a study in the Democratic Republic of Congo. The U.S. study may go through the HIV clinical trial network at multiple sites. The goal is to test the drug in 500 patients with active disease and give a placebo to another 500, Hruby said.
“We can get interim data as we go along, so if it’s particularly effective or ineffective and we see that, we can stop or expand the trial,” he said.
What treatments are available for monkeypox?
Monkeypox has spread to 89 countries, with 32,000 cases worldwide and about 9,500 in the U.S., the largest outbreak by case count, according to the U.S. Centers for Disease Control and Prevention. The World Health Organization has declared the global outbreak a Public Health Emergency of International Concern. There are about 80 confirmed cases in Oregon.
The disease remains rare and isn’t easily transmissible, though it “has the potential to become more common and difficult to treat,” said Mark Slifka, a monkeypox and smallpox expert and professor at Oregon Health & Science University.
Monkeypox is spread primarily through prolonged close skin-to-skin contact. Symptoms include rashes, fever, headache, muscle aches, swollen lymph nodes, chills, exhaustion, sore throat, congestion and coughing. Few people have died from the current outbreak so far.
SIGA, which has a market capitalization of $1.67 billion, has received $60 million of orders for the drug from around the world to date, said CEO Philip Gomez. Two European countries have purchased the drug and have it available, though they required Siga not to disclose which ones. The company announced earlier this week that the U.S. will buy $26 million more of Tpoxx.
“We have dozens of inquiries we’re working through,” Gomez said.
The drug is not available commercially, but can only be procured through sales to governments, similar to the Covid-19 vaccine.
Tpoxx, a small-molecule drug, targets not just smallpox, but various “orthopox viruses” besides monkeypox, including cowpox, mousepox and camelpox. While smallpox was eradicated in the late 1970s, it is still considered a bioterrorism or biowarfare threat.
“When the government was looking at what agents we should worry about, it was given a material threat determination,” Hruby said. “Society is vulnerable and if employed intentionally or released, the results in society would be catastrophic.”
Siga’s corporate headquarters is in New York, but the R&D takes place in Corvallis, where Hruby heads a team of about 30, with 10 more hires on the horizon.
Hruby taught at Oregon State University for 28 years. He moved to New York to work for another vaccine-related startup, which wasn’t successful. He moved back to Oregon in 1996, then another company bought the IP from Viropharma and founded Siga, which went public in 1997. All R&D activities that led to Tpoxx approval were carried out by Siga in Corvallis.
As Hruby sees it, Tpoxx is one piece of a larger arsenal in the fight against monkeypox.
“We’re confident it will work,” Hruby said. “It’s a combination of good diagnostics to see who is infected, utilizing vaccines to prevent further infection and using the drug to treat those who have been infected. If we bring all these tools to bear, we have a chance to contain the current outbreak.”
Siga shares were trading at $22.90 on Wednesday, up 11 cents. Its shares have tripled in value this year.
