US warns monkeypox may mutate to resist antiviral drugs

Washington – we health Officials have warned against overusing the only drug available to treat monkeypox, saying that even a small mutation in the virus could render the pills ineffective.

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

In an online update, FDA officials warned that a single monkeypox molecular change “could have a significant impact on the antiviral activity of Tpoxx.” Since viruses are constantly evolving to overcome obstacles to infection, including drugs, regulators stressed that doctors must be “discreet” in prescribing medication.

The call to scale back Tpoxx use comes after weeks of criticism from HIV advocates and other patient groups who urged the Biden administration to make the antiviral drug more widely available. Tpoxx has been approved for the related smallpox virus, and its use against monkeypox is considered experimental and subject to strict oversight by federal officials.

Physicians wishing to prescribe the drug must submit an application to the Centers for Disease Control and Prevention, documenting the patient’s need and agreeing to track their results and any side effects. Officials shipped 37,000 cycles of the drug to doctors.

Tpoxx works by targeting a single protein found in monkeypox, smallpox, and similar viruses. The US Food and Drug Administration said this week that numerous reports in laboratories, animals and humans indicate multiple ways in which monkeypox can develop resistance to treatment.

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

During a White House briefing, the director of the CDC, Dr. Rochelle Walinsky, attributed the decline to vaccinations, educational outreach, and personnel reducing behaviors linked to the spread. The vast majority of cases in the United States have been in men who have had sex with men, although officials stress the virus can infect anyone.

Dr. Anthony Fauci, the country’s chief infectious disease official, noted that resistance is always a risk when antiviral drugs are used.

“That’s why we feel so uncomfortable when you only have one drug,” Fauci told reporters. He added that a recently launched study of Tpoxx with support from the National Institutes of Health will track signs of mutations that may lead to resistance. The study is expected to enroll more than 500 patients at 60 US sites.

Last month, the Biden administration resorted to rare emergency powers to expand the limited supply of monkeypox in the country. Vaccines. And last week, a separate announcement scrambled to use experimental tests for the virus.

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

The US government’s national inventory contains more than 1.7 million cycles of Tpoxx, originally manufactured for use during a potential bioterrorist attack.

The US Food and Drug Administration approved the drug in 2018 under the Animal Act, which allows approval based on animal data when human testing is unethical or unfeasible. The World Health Organization declared smallpox eradicated in 1980, ruling out the possibility of human studies.

Although the drug has been approved for smallpox, its efficacy has been measured in monkeys with monkeypox, which is a reasonable indication of the effect of smallpox on humans. Animals receiving Tpoxx survived at higher rates than those given a placebo. But FDA officials cautioned that the results on animals should be confirmed in human testing.

“Without human trials, we don’t know if Tpoxx is beneficial for humans with monkeypox,” Food and Drug Administration Commissioner Dr. Robert Califf told Senate lawmakers at a hearing this week.

The CDC reported last week that 3.5% of patients tracked through the Tpoxx program reported side effects, particularly headache and nausea.

The agency only obtained about 200 samples from physicians documenting initial symptoms and patient outcomes, which represents less than 1% of the doses shipped since the start of the outbreak.

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Stobbe reported from New York

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