The Food and Drug Administration this week updated its guidelines for: Tpoxxthat 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 continually evolve to overcome obstacles to infection, including drugs, regulators emphasized that doctors should be “sensible” when prescribing the medication.
The call to scale back 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 more widely available. Tpoxx is approved for the related smallpox virus, and its use against monkeypox is considered experimental and closely monitored by federal officials.
Physicians wishing to prescribe the drug must submit an application to the Centers for Disease Control and Prevention, documenting their patient’s need and agreeing to track 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 on monkeypox, smallpox, and similar viruses. The FDA said this week that multiple reports in lab, animal and human settings suggest multiple ways monkeypox could develop resistance to the therapy.
The update came as federal officials on Thursday were cautiously optimistic about the course of the outbreak, noting that new cases have fallen by about 50% since their peak in August.
At a White House briefing, CDC Director Dr. Rochelle Walensky attributed the decline to vaccinations, education, and individuals reducing spread-related behavior. The vast majority of US cases have been in men who have 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 feel uncomfortable if 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 monitor signs of mutation that could lead to resistance. The study is expected to enroll more than 500 patients at 60 locations in the US.
Last month, the Biden administration invoked rare emergency powers to extend the country’s limited supply of monkeypox vaccines. And last week, a separate statement accelerated the use of experimental testing for the virus.
But no changes have been made to allow emergency use of Tpoxx, sparking 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 during a potential bioterrorism attack.
The FDA approved the drug in 2018 under its “animal rule,” which allows approval based on animal data when testing on humans is unethical or unfeasible. Smallpox was declared eradicated by the World Health Organization in 1980, ruling out the possibility of human studies.
Although the drug was approved for smallpox, its efficacy was measured in monkeys infected with monkeypox, which is considered a reasonable predictor of the effect of smallpox on humans. Animals given Tpoxx survived at higher rates than those on a placebo. But FDA officials have warned that animal results need to be confirmed in human testing.
“Without human trials, we don’t know if Tpoxx is beneficial for people with monkeypox,” FDA Commissioner Dr. Robert Califf to Senate lawmakers at a hearing this week.
The CDC reported last week that 3.5% of patients followed through the Tpoxx program reported side effects, primarily headache and nausea.
The agency has only received about 200 forms back from doctors documenting patient’s initial symptoms and results, representing less than 1% of doses sent since the outbreak began.