The antiviral drug tecovirimat, marketed as TPOXX, has been found ineffective in reducing lesion resolution time or alleviating pain in adults with mild to moderate clade II mpox, according to interim data from the Study of Tecovirimat for Mpox (STOMP). This randomized international clinical trial, led by the U.S. National Institutes of Health (NIH), marks a significant milestone in evaluating treatment options for mpox.

Key Findings and Study Decision

The interim analysis, conducted after 75% of the target enrollment, revealed no significant differences in lesion resolution time or pain reduction between participants receiving tecovirimat and those given a placebo. Additionally, further analysis indicated a less than 1% likelihood of the drug proving effective if the study were to continue.

The study’s Data Safety and Monitoring Board (DSMB) recommended halting participant enrollment, a decision accepted by the NIH’s National Institute of Allergy and Infectious Diseases (NIAID). Enrollment in the open-label study arm, which included participants at higher risk of severe disease, was also discontinued due to the lack of efficacy signals.

Despite these results, the study confirmed tecovirimat’s safety, with low and comparable adverse events reported between the drug and placebo groups.

Broader Implications and Future Research

“The initial STOMP findings provide valuable insight into clade II mpox medical countermeasures,” stated Dr. Jeanne Marrazzo, NIAID Director. “This underscores the importance of conducting well-designed clinical trials during infectious disease outbreaks to systematically evaluate existing antivirals and pursue novel therapeutics.”

While the STOMP findings dampen expectations for tecovirimat’s use against mild to moderate mpox, they align with earlier results from a trial in the Democratic Republic of Congo for clade I mpox.

The NIH continues to support research addressing gaps in mpox countermeasures, including vaccine development and antiviral discovery through programs like the Antiviral Program for Pandemics and the Antiviral Drug Discovery Centers for Pathogens of Pandemic Concern.

Background on Mpox and Tecovirimat

Mpox, caused by a virus with two identified clades (I and II), spreads primarily through close contact. A global outbreak of clade II mpox in 2022 emphasized the need for effective treatments, particularly for vulnerable populations such as immunocompromised individuals and pregnant women.

Originally approved by the FDA for smallpox, tecovirimat has been used under expanded access protocols for mpox, pending further evidence of its efficacy. The STOMP trial, which began in September 2022, aimed to address this gap by evaluating tecovirimat’s potential in both randomized and open-label settings across multiple countries, including the United States, Brazil, and Thailand.

Data from STOMP will guide clinical care and future research. Meanwhile, the CDC’s expanded access investigational new drug (EA-IND) protocol remains available for individuals with severe immunocompromise or advanced HIV.