WASHINGTON (AP) — U.S. health officials are warning against abuse 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 updated its guidelines this week for Tpoxx, which has been prescribed to tens of thousands of patients infected with the virus. In an online briefing, FDA officials warned that a single molecular change in monkeypox “could have a large impact on the antiviral activity of Tpoxx.” Since viruses are constantly evolving to overcome barriers to infection, including drugs, regulators stressed that doctors must be “prudent” in prescribing the drug. The call to limit the use of Tpoxx follows weeks of criticism from HIV advocates and other patient groups who have urged 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. Doctors who wish to prescribe the drug must apply to the Centers for Disease Control and Prevention, documenting their patient’s need and agreeing to monitor their results and any side effects. Officials have sent 37,000 courses of the drug to doctors. Tpoxx works by targeting a single protein found in monkeypox, smallpox and similar viruses. The FDA said this week that multiple reports in laboratory, animal and human settings indicate multiple ways monkeypox could develop resistance to treatment. The update came as federal officials on Thursday expressed cautious optimism about the trajectory of the outbreak, noting that new cases have dropped about 50 percent since their peak in August. During a White House briefing, CDC Director Dr. Rochelle Walensky, attributed the decrease to vaccinations, an educational approach and people reducing behaviors associated with the spread. The vast majority of cases in the US have been in men who have sex with men, although officials stress that the virus can infect anyone. Dr. Anthony Fauci, the nation’s top infectious disease official, noted that resistance is always a risk when antiviral drugs are used. “That’s why we feel uncomfortable when you only take one drug,” Fauci told reporters. He added that a recently started study of Tpoxx supported by the National Institutes of Health will identify signs of mutation that could lead to resistance. The study is expected to enroll more than 500 patients at 60 US sites. Last month, the Biden administration invoked rare emergency powers to expand the nation’s limited supply of smallpox vaccines. And last week a separate statement accelerated the use of experimental tests for the virus. However, no changes were made to allow emergency use of Tpoxx, prompting complaints from groups representing gay and bisexual men. The US government’s national stockpile contains more than 1.7 million rounds of Tpoxx, originally manufactured for use during a potential bioterrorist attack. The FDA approved the drug in 2018 under the “animal rule,” which allows approval based on animal data when human testing is unethical or infeasible. Smallpox was declared eradicated in 1980 by the World Health Organization, precluding human studies. Although the drug was approved for smallpox, its effectiveness was measured in monkeys infected with smallpox, which is considered a reasonable predictor of the effect of smallpox in humans. Animals given Tpoxx survived at higher rates than those given placebo. However, FDA officials have cautioned that results in animals must be confirmed in human trials. “Without human trials, we don’t know whether Tpoxx is beneficial for people with monkeypox,” FDA Commissioner Dr. Robert Califf told Senate lawmakers at a hearing this week. The CDC reported last week that 3.5 percent of patients monitored through the Tpoxx program reported side effects, mainly headache and nausea. The agency has taken back only about 200 forms from doctors documenting the patient’s initial symptoms and results, representing less than 1% of the doses sent since the outbreak began.
Stobbe reported from New York
The Associated Press Health and Science Section is supported by the Howard Hughes Medical Institute Science Education Division. AP is solely responsible for all content. Matthew Perrone and Mike Stobbe, The Associated Press
