The antiviral drug tecovirimat (TPOXX), initially approved for smallpox, has failed to demonstrate efficacy in treating mild to moderate mpox, according to interim data from the NIH-sponsored Study of Tecovirimat for Mpox (STOMP). The international clinical trial, conducted across multiple countries, found that tecovirimat did not significantly reduce the time to lesion resolution or alleviate pain compared to placebo in adult participants with clade II mpox and a low risk of severe disease.
STOMP Trial Design and Findings
The STOMP trial, launched in September 2022, was a randomized, double-blind, placebo-controlled study designed to evaluate the effectiveness of a 14-day course of tecovirimat in patients with mpox. Participants were enrolled across Argentina, Brazil, Japan, Mexico, Peru, Thailand, and the United States. The primary endpoint was the time to clinical resolution of visible mpox lesions, with pain reduction as a secondary outcome measure.
An interim analysis conducted after 75% of the target enrollment was reached revealed no significant difference in lesion resolution time between the tecovirimat and placebo groups. Pain reduction was also similar in both groups. Following these findings, the study's Data Safety and Monitoring Board (DSMB) recommended halting further enrollment. The National Institute of Allergy and Infectious Diseases (NIAID), the study sponsor, accepted this recommendation and closed the trial, including an open-label arm for participants at high risk of severe disease.
"The initial STOMP findings provide valuable insight to inform clade II mpox medical countermeasures and underscore the critical importance of conducting well-designed randomized clinical trials during infectious disease outbreaks," said NIAID Director Jeanne Marrazzo, M.D., M.P.H.
Implications for Mpox Treatment
Tecovirimat, developed by SIGA Technologies, was initially approved by the FDA for the treatment of smallpox due to its activity against orthopoxviruses. Given the similarities between the smallpox and mpox viruses, tecovirimat was considered a potential treatment option for mpox, particularly during the 2022 global outbreak of clade II mpox. However, prior to this year, its efficacy specifically against mpox had not been established through rigorous clinical trials.
Despite the negative results from the STOMP trial, tecovirimat remains available through the CDC’s expanded access Investigational New Drug (EA-IND) protocol for individuals with severe immunocompromise, including those with advanced HIV, for whom the role of tecovirimat treatment has not been fully established. The CDC provides information on accessing tecovirimat through its website.
Ongoing Research and Future Directions
While the STOMP trial results are disappointing, researchers emphasize the importance of the study in providing crucial data to guide mpox treatment strategies. Timothy Wilkin, M.D., M.P.H., study chair and chief of the Division of Infectious Diseases and Global Public Health at the University of California, San Diego, noted, "STOMP was a banner study for its speed of startup, inclusiveness, and collaboration across governments and public health authorities. This study may serve as a model for outbreak response, delivering essential scientific evidence while also enabling equitable treatment access."
NIAID continues to support research aimed at addressing evidence gaps in medical countermeasures for mpox and other health threats. This includes ongoing efforts to develop safe and effective vaccines, monoclonal antibodies, and antiviral medicines against virus families of pandemic potential. Further studies, such as the UNITY trial in Argentina, Brazil, and Switzerland, are also evaluating tecovirimat with similar study designs to STOMP.
