Since the first case of monkeypox on May 6, reports of outbreaks have come from multiple countries, with the United Kingdom, Spain, and Portugal in the lead, followed by Canada, Israel, and Australia, among others. The United States has reported cases in Boston and New York, and presumed cases have occurred in Utah and Florida. As of May 25, close to 350 cases, either suspected (83) or confirmed (265), have been reported globally.
Monkeypox outbreaks have previously been confined to Central and West Africa, except for an impressively large outbreak in the United States in 2003, during which 47 people were infected across six states. The epidemic was traced to a Gambian rat, rope squirrels, and dormice that had been imported from Ghana as pets and that had infected prairie dogs at a large wholesale pet store.
“It’s amazing how many of these viruses – COVID, now monkeypox and others – [exist]. They’re out there in the wild in the animal reservoir,” said Dennis Hruby, PhD, executive VP/chief scientific officer and scientific founder of SIGA Technologies.
“When it comes to the human population, they sometimes behave in ways we’re not expecting. That and a few mutations change those strains and pathogenicity and can be pandemic,” he told this news organization.
Now that the virus is pandemic, there is an urgent interest in medicines and vaccines that might halt its spread.
Smallpox drug tecovirimat
SIGA’s drug is tecovirimat, initially known as ST-246 and now branded as TPOXX. The U.S. Food and Drug Administration approved an oral formulation to treat smallpox in 2018. While smallpox was eradicated by 1980, there have been ongoing concerns about its potential use in a bioterrorism attack.
Tecovirimat is also approved for smallpox in Canada. In Europe, the approval includes treatment of monkeypox, cowpox, and complications from immunization with vaccinia. On May 19, the FDA approved an IV formulation of tecovirimat for those unable to tolerate oral medications.
In a press release, SIGA notes that tecovirimat was “developed through funding and collaboration with the Biomedical Advanced Research and Development Authority (BARDA) at the U.S. Department of Health & Human Services, as well as early-stage development supported by the National Institutes of Health, US Centers for Disease Control and Prevention, and the Department of Defense. Tecovirimat is stockpiled by the U.S. Government to mitigate the impact of a potential outbreak or bioterror attack.”
SIGA adds that, under Project Bioshield, “the United States maintains a stockpile of 1.7 million courses in the Strategic National Stockpile.” The drug is only available through the government’s stockpile.
Tecovirimat works by preventing the viruses from reproducing by interfering with a protein, VP37. The virus cannot escape the cell and so cannot infect other cells, Dr. Hruby explained.
Tecovirimat was developed under the FDA’s so-called Animal Rule, which allows approval on the basis of animal studies when human efficacy studies are unethical or impractical.
In a placebo-controlled human pharmacokinetic and safety study, only 2% of the 359 who received TPOXX had to have treatment stopped because of adverse reactions, a rate similar to placebo. The most common reactions (≥2%) were headache, nausea, and abdominal pain. Significant drug interactions were found with the coadministration of repaglinide and midazolam.
Of note is that tecovirimat’s efficacy may be reduced in immunocompromised patients. The smallpox vaccine is contraindicated for those who are immunocompromised. Those people should be offered vaccinia immune globulin.
With monkeypox, “the earlier the disease is recognized and you start treating, [the] more effective,” said Dr. Hruby. “In a monkey model which, much like humans, if we treat early on as the first lesions emerged or even several days after the lesions emerged, we see close to 100% protection.”
The other alternative drug for smallpox and (likely) monkeypox is Chimerix’s brincidofovir (BCV, Tembexa), a lipid conjugate of cidofovir, a drug for cytomegalovirus. Brincidofovir has a better safety profile than cidofovir and was also approved under the Animal Rule.
UpToDate suggests that tecovirimat is the drug of choice for monkeypox. They note that for severely infected patients, it can be combined with brincidofovir after consultation with the CDC or state health department officials.