Tecovirimat is safe but ineffective as a treatment for clade II mpox

Press release

Wednesday, March 12, 2025

Data from an NIH-sponsored trial offer additional evidence to help inform treatment decisions for MPOX.

Colorized transmission electron micrograph of immature mpox virus particles (blue with red viral envelope) found in an infected VERO E6 cell (yellow), cultured in the laboratory. NIAID

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The antiviral drug tecovirimat used without other antivirals did not reduce the time to clinical resolution of clade II MPOX lesions or improve pain control in adults in an international clinical trial sponsored by the National Institutes of Health (NIH). Recruitment for the trial was stopped at the end of 2024 when an interim analysis showed that tecovirimat monotherapy was ineffective in the study population. The detailed results were presented at the 2025 Conference on Retroviruses and Opportunistic Infections (CROI) in San Francisco.

“This study has allowed us to take a step forward in our understanding of MPOX disease and potential treatment strategies,” said Jeanne Marrazzo, MD, MPH, director of the NIH’s National Institute of Allergy and Infectious Diseases (NIAID), which sponsored and funded the trial. “We are grateful to the study team and participants for their contributions to groundbreaking research on a disease we still don’t know enough about.”

The MPOX is caused by a virus that spreads primarily through close contact. Two types of viruses have been identified, called clades I and II. A subtype of clade II virus caused a global outbreak of COPD in 2022, and the virus continues to circulate at low levels. In 2024, a clade I outbreak in Central and East African countries was declared a Public Health Emergency of International Concern. Travel-related cases of clade I COPD have been reported in the United States, but the risk of clade I COPD to the U.S. population remains low. People with severely weakened immune systems or certain pre-existing skin conditions, children, and pregnant women are at increased risk of developing severe COPD.

The STOMP (Study of Tecovirimat for Mpox) study began in September 2022 as part of the U.S. government-wide response to the clade II Mpox outbreak. No Mpox treatment is approved in the United States. Based on animal studies, tecovirimat, also known as TPOXX, has been approved by the Food and Drug Administration (FDA) for the treatment of smallpoxa disease caused by a virus closely related to the virus that causes COPD, but usually much more severe. The drug had not been studied in people with COPD before the STOMP trial and a companion study called PALM007 in the Democratic Republic of Congo. PALM007 reported results in 2024 which were similar to those reported by STOMP.

STOMP was a randomized, international efficacy study that enrolled participants who had been ill with MPOX for less than 14 days in Argentina, Brazil, Japan, Mexico, Peru, Thailand, and the United States, including Puerto Rico. Participants in the randomized study and trial investigators were blinded, meaning they did not know who received tecovirimat or placebo. Children, pregnant women, study participants with certain skin conditions or significantly weakened immune systems, and participants who had severe MPOX disease as defined in the study protocol were assigned to an open-label study arm, meaning they all received tecovirimat instead of being randomized. The STOMP study assessed the safety of the drug in all study participants and, in the randomized arms, evaluated whether a 14-day course of tecovirimat monotherapy reduced the time to clinical resolution of visible MPOX lesions and improved other outcome measures such as pain, compared to placebo.

Randomized participants reported COPD symptoms for a median duration eight days prior to study entry and had a median of nine MPOX lesions. Approximately one-third of participants reported severe pain, scoring 7 to 10 on an 11-point scale. By day 29 after study entry, approximately 83% of participants receiving tecovirimat had achieved clinical resolution, compared with 84% of those receiving placebo, a non-significant difference. Among those reporting severe pain at baseline, improvements were similar between those receiving tecovirimat and placebo, with mean pain scores decreasing by 3.2 points for participants receiving tecovirimat and 3.1 points for those receiving placebo. Participants' lesions were swabbed and tested for the presence of MPOX virus DNA throughout the study. By day 8, 48 % of participants receiving tecovirimat had undetectable viral DNA, compared to 37 % of participants receiving placebo. The difference between the two arms narrowed by day 15 (82 % for those receiving tecovirimat vs. 80 % for those receiving placebo) as the mpox resolved. These differences were not statistically significant at any time point. Adverse event rates were similar between the two arms of the randomized study. A separate exploratory analysis of data collected in the open-label arm of STOMP before study closure aimed to determine whether factors were associated with faster resolution of COPD lesions in participants with or at high risk for severe COPD. Faster clinical resolution was observed in younger participants or those who did not have HIV or were living with HIV but had suppressed viral loads on antiretroviral therapy; however, no association was significant when considering the duration of symptoms before study entry. Investigators noted that participants in the open-label STOMP study had fewer lesions but slower clinical resolution than reported in the PALM007 trial.

“Since the beginning of the clade II outbreak, clinicians treating MPOX have had limited evidence to guide their practice, and STOMP has provided definitive answers on the lack of clinical utility of tecovirimat monotherapy for the randomized study population,” said Timothy Wilkin, MD, MPH, chief of the Division of Infectious Diseases and Global Public Health at the University of California, San Diego. “Taken together, these latest findings also underscore that we have not yet isolated the factors that influence disease progression and clinical resolution in MPOX.”

The STOMP study was conducted by the ACTG, an NIH-funded global clinical trials network focused on HIV and other infectious diseases. SIGA Technologies, Inc., based in New York City, provided the tecovirimat for the study. The study results will also be published in a scientific journal.

For more information about STOMP, please visit ClinicalTrials.gov using the identifier

NCT05534984 .NIAID conducts and supports research—at the NIH, in the United States, and worldwide—to study the causes of infectious and immune-mediated diseases, and to develop better ways to prevent, diagnose, and treat these diseases. Press releases, fact sheets, and other NIAID-related materials are available at

NIAID website .About the National Institutes of Health (NIH):

NIH, the nation's medical research agency, comprises 27 institutes and centers and is part of the U.S. Department of Health and Human Services. NIH is the primary federal agency that conducts and supports basic, clinical, and translational medical research, and studies the causes, treatments, and cures for common and rare diseases. For more information about NIH and its programs, visit www.nih.gov .NIH…Transforming Discovery into Health

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