An analysis of interim data from the international Study of Tecovirimat for Mpox (STOMP) revealed that the antiviral drug, tecovirimat, did not expedite the healing of lesions or mitigate pain in adults experiencing mild to moderate clade II mpox who were at minimal risk for severe illness. Importantly, the analysis did not identify any safety issues with tecovirimat.
Following these conclusive results, the study’s Data Safety and Monitoring Board (DSMB) advised halting further participant enrollment in the randomized trial of tecovirimat versus placebo. The National Institute of Allergy and Infectious Diseases (NIAID) of the NIH, as the study sponsor, complied with the DSMB’s guidance. Acknowledging the lack of efficacy, NIAID also concluded the open-label study arm for individuals with or at high risk for severe disease, designed not to gauge the drug’s effectiveness.
As stated by NIAID Director Jeanne Marrazzo, M.D., M.P.H., “The preliminary STOMP results are pivotal in guiding medical strategies for clade II mpox and highlight the crucial need for meticulously planned randomized clinical trials during infectious disease outbreaks. Before 2022, no treatments had been assessed for effectiveness in mpox cases, and this trial marks a vital phase in systematically evaluating existing antivirals like tecovirimat, while also seeking new antiviral medications and antibody therapies for mpox.”
Mpox is triggered by a virus primarily transmitted through close interactions, with clades I and II observed historically in Central and West Africa, respectively. A subtype of clade II prompted a global mpox outbreak in 2022, and despite low-level circulation, a clade I outbreak in 2024 led the World Health Organization to declare it a public health emergency of international significance. Internationally, travel-related clade I cases have emerged, with the US confirming its initial case on November 15. In the United States, the public risk of clade I mpox remains minimal. Certain populations, including those with significantly compromised immune systems or specific pre-existing skin conditions, children, and pregnant individuals, face heightened risks of severe mpg.
The STOMP initiative was launched in September 2022 as a part of the broader U.S. government response to the clade II mpox outbreak. It enrolled participants with illness for under 14 days, randomizing them at a 2:1 ratio to receive tecovirimat or a placebo across different nations including Argentina, Brazil, Japan, Mexico, Peru, Thailand, and the U.S., including Puerto Rico. Both participants and researchers in the trial were blinded to who received which treatment. For vulnerable groups like children and pregnant participants, an open-label arm ensured they received tecovirimat directly, bypassing randomization.
The STOMP study analyzed participant safety and, in randomized arms, assessed whether a 14-day tecovirimat regimen influenced the resolution time of visible mpox lesions or improved outcomes such as pain when compared to placebo.
A pre-scheduled interim assessment completed at 75% of target enrollment found tecovirimat did not alter the lesion healing timeline relative to placebo-treated subjects. Pain levels also dropped similarly between those on tecovirimat and those on placebo. After a DSMB request for further examination, it was determined there was less than a 1% possibility that completing the study would validate tecovirimat’s effectiveness based on the study’s framework and existing data. Adverse event frequencies were low and comparable between the two groups. The open-label segment, inherently lacking a placebo control, doesn’t conclude tecovirimat’s efficacy for severe mpox cases.
Further evaluation of the data is underway. Participants are being updated on the findings, and study doctors will adjust individual care strategies based on disease severity. The CDC maintains a protocol for mpox treatment access outside research settings under expanded access investigational new drug (EA-IND), targeting individuals with severe immunocompromise, such as those with advanced HIV, for whom the role of tecovirimat remains unverified in trials. Details on this protocol can be found on the CDC website.
Study chair Timothy Wilkin, M.D., M.P.H., emphasized, “STOMP stood out for rapid initiation, inclusivity, and cross-governmental collaboration. It serves as a response blueprint, blending scientific inquiry with equal access to treatment.”
These findings align with earlier results from a NIAID-co-sponsored tecovirimat trial focused on clade I mpox in the Democratic Republic of the Congo.
The NIAID-led research was implemented by the NIH-funded ACTG, a global network excelling in infectious disease trials. New York-based SIGA Technologies, Inc. provided tecovirimat for this endeavor. NIAID and STOMP investigators consistently collaborated with entities such as the CDC, FDA, and health authorities across various study locales, fostering effective research question resolution, compassion-led use, and dissemination of clinically relevant data on clade II mpox treatment globally. Another investigation, UNITY, spearheaded by ANRS Emerging Infectious Disease, explores tecovirimat similarly to STOMP in Argentina, Brazil, and Switzerland.
NIAID’s commitment extends toward bridging existing gaps in mpox-associated medical responses and other health challenges, encompassing initiatives like the Research and Development of Vaccines and Monoclonal Antibodies for Pandemic Preparedness Network, and the Antiviral Program for Pandemics. These programs advance research and develop vaccines, monoclonal antibodies, and antiviral agents countering families of viruses with pandemic capabilities.
NIAID’s mission spans research in infectious and immune-related diseases—conducted at NIH, across the U.S., and globally—aiming to enhance prevention, diagnosis, and treatment methods.
The National Institutes of Health (NIH) under the US Department of Health and Human Services, serves as the principal federal entity driving medical research, delving into the origins, treatments, and cures for various illnesses, common and rare.