US warns monkeypox may mutate to resist antiviral drug

WASHINGTON (AP) — U.S. health officials are warning against overuse of the only drug available to treat monkeypox, saying even a small mutation in the virus could render the pills ineffective.

The Food and Drug Administration this week updated its guidance on Tpoxx, which has been prescribed to tens of thousands of patients affected by the virus.

In an online update, FDA officials warned that a single molecular change in monkeypox “could have a major impact on Tpoxx’s antiviral activity.” As viruses continue to evolve to overcome barriers to infection, including drugs, regulators stressed that doctors should be “prudent” when prescribing the drugs.

The call to limit the use of Tpoxx follows weeks of criticism from HIV advocates and other patient groups who have called on the Biden administration to make the antiviral drug more widely available. Tpoxx is approved for the related smallpox virus, and its use against monkeypox is considered experimental and tightly controlled by federal officials.

Physicians wishing to prescribe the drug must submit an application to the Centers for Disease Control and Prevention, document their patient’s needs, and agree to track their results and side effects. Officials have mailed 37,000 courses of the drug to doctors.

Tpoxx works by targeting a single protein found on monkeypox, smallpox, and similar viruses. The FDA said this week that multiple reports in laboratory, animal, and human settings suggest multiple ways in which monkeypox could develop resistance to the therapy.

The update came as federal officials on Thursday expressed cautious optimism about the course of the outbreak, noting that new cases have fallen about 50% since their peak in August.

During a White House briefing, CDC Director Dr. Rochelle Walensky attributes the decline to vaccinations, awareness-raising and individuals reducing behavior associated with the spread. The vast majority of US cases have involved men who have had sex with men, although officials stress the virus can infect anyone.

dr Anthony Fauci, the country’s top infectious disease official, noted that resistance is always a risk when using antiviral drugs.

“That’s why we’re uncomfortable when you only have one drug,” Fauci told reporters. He added that a recently launched study of Tpoxx, supported by the National Institutes of Health, will track signs of mutations that could lead to resistance. The study is expected to enroll more than 500 patients at 60 sites across the United States.

Last month, the Biden administration invoked rare emergency powers to expand the nation’s limited supply of monkeypox vaccines. And last week, a separate statement sped up the use of experimental testing for the virus.

However, no changes were made to allow Tpoxx to be used in an emergency, prompting complaints from groups representing gay and bisexual men.

The US government’s national stockpile contains more than 1.7 million courses of Tpoxx, originally manufactured for use in a potential bioterrorism attack.

The FDA approved the drug in 2018 under its “animal rule,” which allows approval based on animal data when human testing is unethical or impractical. Smallpox was declared eradicated by the World Health Organization in 1980, eliminating the possibility of human studies.

Although the drug was approved for smallpox, its effectiveness was measured in monkeypox-infected monkeys, which are considered a reasonable predictor of smallpox’s effects on humans. Animals receiving Tpoxx survived at higher rates than those receiving placebo. But FDA officials have warned that results in animals need to be confirmed in human tests.

“Without human studies, we don’t know if Tpoxx is beneficial for people with monkeypox,” said FDA Commissioner Dr. Robert Califf at a Senate hearing this week.

The CDC reported last week that 3.5% of patients followed through their Tpoxx program reported side effects, primarily headaches and nausea.

The agency has only received about 200 forms from doctors documenting the patient’s initial symptoms and findings, accounting for less than 1% of the doses shipped since the outbreak began.

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Stobbe reported from New York

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The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institute’s Department of Science Education. The AP is solely responsible for all content.

Matthew Perrone and Mike Stobbe, The Associated Press