In 2022, the United States and other Western countries experienced a significant increase in mpox cases, a disease previously considered endemic to central and western Africa. In response, infectious disease physicians began using tecoviromat, an antiviral drug initially developed for smallpox, with hopes that it would also be effective against mpox due to similarities between the viruses.
However, a large clinical trial co-led by Columbia University’s Division of Infectious Diseases found that tecoviromat did not perform better than a placebo in treating mpox. The results were published last month in the New England Journal of Medicine (NEJM).
Jason Zucker, assistant professor of medicine at Columbia University Vagelos College of Physicians and Surgeons and leader of the study, discussed the findings and ongoing efforts to manage mpox. He noted that while cases have decreased since 2022, “the virus is not going away. In New York City, we’ve seen up to 20 cases a week in the summer.” Zucker highlighted vaccination efforts during the outbreak: “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.”
He added that as case numbers declined, public interest in vaccination waned. “Many people only got one of the two shots needed for long-term efficacy,” he said. Zucker also pointed out that younger individuals who were teenagers during the outbreak could benefit from vaccination as they become more sexually active.
The JYNNEOS vaccine was previously available for free through federal stockpiles but has since been commercialized. Zucker stated: “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.”
Despite these efforts, there remains a need for an effective antiviral treatment. Tecoviromat had shown promise in animal studies but failed to demonstrate effectiveness in human trials conducted both in Africa and Western countries. According to Zucker: “The first human clinical trial of tecoviromat was done in Africa… In that trial, tecoviromat did not reduce the number of days to lesion resolution.” He continued: “Unfortunately, we found tecoviromat didn’t work against mpox in these settings either.”
Zucker explained why this result impacts future expectations for smallpox treatment: “I think we would all feel relatively confident that if tecoviromat worked against mpox, then it would work against smallpox… But it didn’t work, so we have no reason to think it would work for smallpox if it didn’t work for mpox.”
He emphasized lessons learned about clinical research during outbreaks: “The study really highlights the importance of doing clinical trials early in an outbreak setting.” He criticized reliance on expanded access programs over formal trials: “The drug was given to over 7,000 people through an expanded access program instead of enrolling them in a clinical trial… Those 7,000 people could have contributed to a clinical trial to help us get answers faster.”
The study received support from the National Institutes of Health.
