In 2022, mpox infections surged in the United States and other Western countries, showing that a viral illness long considered endemic in central and western Africa was capable of traveling far and wide.
To treat patients, infectious disease physicians turned to an antiviral drug, tecoviromat, originally developed to treat smallpox in case of an outbreak. Though physicians hoped the drug would also work against mpox, a related virus, a large clinical trial co-led by Columbia's Division of Infectious Diseases found otherwise. As reported in NEJM last month, the study found that the drug was no better than a placebo.
Study leader Jason Zucker, assistant professor of medicine at Columbia University Vagelos College of Physicians and Surgeons, spoke with CUIMC News to discuss where we stand with development of a treatment for mpox.
Why do we need an antiviral treatment for mpox, since we have an effective vaccine?
While mpox cases have gone down since the outbreak here in 2022, the virus is not going away. In New York City, we've seen up to 20 cases a week in the summer. During the height of the outbreak, especially here in New York City, we did a really great job of vaccinating populations that might be vulnerable to mpox.
But as cases dipped, mpox was not on people's minds as much and they became less willing to be vaccinated. Many people only got one of the two shots needed for long-term efficacy.
There's also a new generation of people who were 15 or 16 in 2022 and could really benefit from this vaccine as they become more sexually active.
Vaccination with JYNNEOS [approved in 2019 for smallpox and mpox] was previously available for free through the Strategic National Stockpile. Over the course of this outbreak, the vaccine was commercialized, so now it costs something to get the shot, but we are working hard to make sure that everybody who is eligible for vaccination receives it.
We hope more people get vaccinated, but in the meantime, we need an effective antiviral.
Tecoviromat was developed to treat smallpox. Is that why it doesn't work against mpox?
Orthopoxviruses are very similar. Though tecoviromat was developed to treat smallpox, it was expected to work across all orthopoxviruses.
The drug was evaluated in animal models infected with mpox and rabbitpox, because testing in people was too risky, but the best way to evaluate a drug is to evaluate it in humans.
The first human clinical trial of tecoviromat was done in Africa, during a 2022-2023 outbreak in Democratic Republic of Congo. In that trial, tecoviromat did not reduce the number of days to lesion resolution.
It wasn't until mpox affected Western countries that there was enough support to do these clinical trials here in settings where patients were getting antibiotics and other forms of supportive care. Unfortunately, we found tecoviromat didn't work against mpox in these settings either.
I think we would all feel relatively confident that if tecoviromat worked against mpox, then it would work against smallpox, another orthopoxvirus, because the mechanisms of replication and many other parts of the viruses' genomes are so similar. But it didn't work, so we have no reason to think it would work for smallpox if it didn't work for mpox.
Could we have done things differently in terms of testing a drug for mpox?
The study really highlights the importance of doing clinical trials early in an outbreak setting.
The drug was given to over 7,000 people through an expanded access program instead of enrolling them in a clinical trial to find out if it really worked. Those 7,000 people could have contributed to a clinical trial to help us get answers faster.
References
More information
"Tecoviromat for the treatment of mpox" was published February 26, 2026, in NEJM.
Jason Zucker, MD, co-led the study (additional authors and disclosures are listed in the paper).
The study was supported by the National Institutes of Health (UM1 AI068634, UM1 AI068636, and UM1 AI106701).
