FDA Warns That Antiviral Overuse Could Mutate Monkeypox

The monkeypox virus is only one mutation away from avoiding a major antiviral drug used to treat at-risk individuals, according to federal health experts, who are advising doctors to be “judicious” in administering the desired treatment.

The new FDA guidance for the antiviral medicine tecovirimat, or Tpoxx, was released online and in amended labeling this week.

According to the regulator, lab and animal research, as well as information from a human instance of this virus family, suggest monkeypox has “multiple genetic mechanisms” to evolve resistance to tecovirimat. According to the FDA, many “need only a single amino acid modification.”

“Most patients with intact immune systems really need supportive care and pain control, but often do not need to be stepped up to antiviral treatment,” said Dr. Sapna Bamrah Morris of the Centers for Disease Control and Prevention over the weekend during a webinar hosted by the Infectious Diseases Society of America.

The CDC has been actively monitoring virus mutations in order to identify potential resistant variants to the monkeypox treatment. A subset of positive tests from throughout the country are being sent to the agency for genetic sequencing.

The CDC sent a warning to laboratories earlier this month about a “rare” mutation discovered in California that caused “false negative” findings on some tests.

So far, no cases of a tecovirimat-resistant strain have been identified, but authorities warn that the “low barrier to resistance” offers a risk that a resistant variety would arise and spread.

“We do know that there is a point mutation that could lead to resistance to tecovirimat or Tpoxx, which is our primary antiviral,” Bamrah Morris explained.

The FDA’s warning comes as federal health officials have been asking doctors to refer monkeypox patients to the National Institutes of Health’s recently started clinical trials to evaluate the medicine rather than prescribing it themselves.

Tecovirimat is still available for doctors to procure for their patients through the CDC’s “extended access” procedure. White House officials have praised their efforts to reduce the paperwork required to obtain the medicine through this so-called “compassionate use” route.

The CDC has reported preliminary promising results from patients who received the medicine using this regimen. On average, symptoms improved in three days.

However, given the absence of a control group, the CDC cautioned against drawing inferences about the efficacy of tecovirimat based on individuals treated in this manner.

“Data from randomized controlled trials are critically needed to address knowledge gaps related to efficacy, safety, and pharmacokinetics in humans with monkeypox, as well as to monitor for the development of tecovirimat resistance,” FDA’s Dr. Adam Sherwat told doctors during a recent webinar hosted by the American Medical Association.

The manufacturer of tecovirimat, Siga Technologies, has been actively assisting the federal trial with supplies to research their medicine. Tecovirimat is currently only licensed for smallpox, an orthopoxvirus related to smallpox.

According to the company’s chief scientific officer, the FDA’s “low barrier to resistance” comment “may be overblown.”

“DNA viruses are what poxviruses are. They have the ability to modify their DNA while reproducing and fix errors. As a result, the mutation rate in a poxvirus is hundreds to thousands of times lower than that of an RNA virus such as COVID or influenza “Dennis Hruby of Siga agreed.

Hruby reported instances in which the medicine appeared to assist patients clean out the virus, even after 82 days in the case of one person who had a resistant strain.

“Working with our colleagues in other countries, they are not recommending the medicine to those with minor cases. However, if the cases advance to the point where the patient is in severe pain and discomfort and/or is going to be hospitalized, they are treated “Hruby stated.

Many patients with monkeypox have described severe rashes and sores, and recovery might take weeks. The CDC now has a total of 22,630 cases across the country.

A few people have been admitted to hospitals due to virus-related issues.

The Centers for Disease Control and Prevention (CDC) revealed two cases of previously healthy young men who were hospitalized after the virus progressed to their brain and spinal cord.

On Monday, health officials in Los Angeles became the first to confirm the virus’s death in the United States, in a person who was “severely immunocompromised.” Another fatality in Texas is currently being reviewed to identify the role of the virus.

The Biden administration has also taken steps to stock up on another smallpox antiviral. The medicine brincidofovir or Tembexa, manufactured by Chimerix, may provide doctors with an alternative if tecovirimat is ruled out.

“We anticipate that it will be ready soon. In addition, the CDC is now creating an expanded access IND protocol to aid in the use of this medicine as a treatment for monkeypox “At the AMA webinar, CDC’s Brett Petersen informed clinicians.

Credits: CBS News