By Ethan Covey
A cluster of mpox cases caused by tecovirimat-resistant monkeypox virus (MPXV) has been identified in the United States, raising concerns regarding a drug-resistant version of the disease.
The cases in the cluster all occurred among people who had no history of tecovirimat treatment (MMWR Morb Mortal Wkly Rep 2024;73[40]:903-905).
“At the start of the 2022 global mpox outbreak, we were concerned that overuse of tecovirimat could result in tecovirimat-resistant virus,” said Crystal M. Gigante, PhD, an epidemiologist with the CDC’s Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases. “Before this study, most cases of tecovirimat resistance had been reported in patients who previously took tecovirimat.”
Tecovirimat has become widely used as an mpox treatment as a result of the ongoing clade II mpox outbreak. However, since it is not FDA approved for treatment of mpox but became available via compassionate use, health authorities including the CDC have cautioned that the use of tecovirimat for the treatment of mpox is investigational.
“Tecovirimat is considered safe, but whether or not it’s effective is still being determined,” Dr. Gigante said. “The PALM007 study gives us some information, but more information is needed through clinical trials and clinical use of tecovirimat. More information will help aid understanding of the role tecovirimat can play in mpox treatment and who might benefit most, possibly including people who are severely immunocompromised.”
There are ongoing clinical trials to assess tecovirimat, including the National Institutes of Health STOMP (Study of Tecovirimat for Mpox).
“CDC continues to encourage healthcare providers to inform patients with mpox about STOMP and to recommend they consider seeking enrollment in the trial; this is a needed clinical trial to better understand tecovirimat’s efficacy,” Dr. Gigante said. “Patients do not have to have severe disease or be at high risk of severe disease to enroll in the study.”
The report details a unique combination of F13 mutations collected from 18 patients in five states (California, Illinois, Louisiana, New York and Texas) during the period of Oct. 2, 2023, through Feb. 15, 2024. F13 mutations associated with drug resistance have been reported since 2022.
“It’s not possible to identify the first case with this mutation, but it’s likely that the person had taken tecovirimat in the past,” Dr. Gigante said. “Because not all samples from mpox cases are sequenced, the 18 known cases of this variant are likely an underestimate of how many cases there truly are.”
Among the 16 patients in the cluster who had available information regarding treatment history, none had documentation of previous tecovirimat use. Two of the individuals reported travel to states where the mutation had been identified, and two others reported traveling to other U.S. states.
“Regarding the risk associated with tecovirimat-resistant mpox infections, there are limited approved therapeutics for mpox,” Dr. Gigante said. “Although it is unclear whether there is a role for tecovirimat in immunocompetent patients, not having first-line mpox treatment could cause poor outcomes in those at risk for life-threatening manifestations of mpox, for example, people with severely immunocompromising conditions.”
She also noted the importance of developing alternate treatments, and continuing surveillance efforts for the disease. “This MMWR highlights the need for more mpox treatment options beyond tecovirimat,” she added. “We were able to detect the spread of this resistant MPXV variant because of the public health labs performing genomic surveillance of mpox. Continued tracking of the virus is needed to detect events like this.”
