Colorized transmission electron micrograph of two particles of the virus that causes mpox, cultivated and purified from cell culture.
Image credits: NIAID
A major clinical trial of the antiviral drug tecovirimat (TPOXX) has concluded that while the drug is safe, it does not significantly improve lesion resolution or reduce pain in individuals with mild to moderate cases of mpox. The interim findings, released by the National Institutes of Health (NIH) on December 10, 2024, mark a setback in the search for effective treatments.1
The Study of Tecovirimat for Mpox (STOMP) enrolled participants from multiple countries, including the US, Brazil, Argentina, and Mexico, to assess whether a 14-day course of tecovirimat could speed up the resolution of visible mpox lesions or alleviate pain in adults with clade II mpox, the strain responsible for the global outbreak in 2022.1
An interim analysis of the study, conducted when 75% of participants were enrolled, found no difference in lesion resolution or pain reduction between those treated with tecovirimat and those receiving a placebo. Based on these results, the study’s Data Safety and Monitoring Board (DSMB) recommended halting further enrollment in both groups. The NIH accepted this recommendation and also closed enrollment in an open-label study arm for individuals at higher risk of severe disease, who were given tecovirimat regardless of randomization.1
“There is no evidence from this study to suggest that tecovirimat is effective in treating mild to moderate clade II mpox,” said Jeanne Marrazzo, MD, MPH, director of NIH’s National Institute of Allergy and Infectious Diseases (NIAID). “While these findings are disappointing, they are an important part of our ongoing effort to evaluate existing antivirals in response to infectious disease outbreaks.”
TPOXX, an antiviral drug initially stockpiled for smallpox preparedness, is being investigated for treating mpox, caused by the monkeypox virus. Two clinical trials, PALM007 and STOMP, have shown that while tecovirimat is safe, it does not significantly speed up lesion resolution or reduce pain in mild to moderate mpox cases. These trials were conducted in clade I and clade II mpox-affected regions.2
As of December 10, 2024, the STOMP trial has ended, and enrollment has been closed. Although, tecovirimat remains available through the CDC’s expanded access Investigational New Drug (EA-IND) protocol for eligible patients, including those with severe immunocompromise or other high-risk conditions. Providers can access the drug by contacting state or local health departments or the CDC Emergency Operations Center for assistance.2
Mpox, caused by the monkeypox virus (MPXV), belongs to the Orthopoxvirus genus, including smallpox. While similar to smallpox, mpox is far less deadly. Initial symptoms include fever, headache, body aches, fatigue, swollen lymph nodes, and a rash, often affecting the skin, mouth, or genital area. Human-to-human transmission occurs through direct contact with lesions, body fluids, prolonged close contact (including sexual contact), and contaminated items.3
The STOMP trial, launched in September 2022, was part of a broader US government response to the mpox outbreak. The study enrolled individuals who had been ill for fewer than 14 days with mild to moderate symptoms. Participants were randomly assigned to receive either tecovirimat or a placebo, and both participants and investigators were blinded to treatment assignments. The primary outcomes were the time to resolution of mpox lesions and pain levels.1
In 2022, a global outbreak of Clade II mpox spread to non-endemic regions, including North America and Europe. While cases have decreased significantly since then, Clade II circulates in several countries, typically in small clusters. In August 2024, a Clade I outbreak in the Democratic Republic of the Congo (DRC) and other African countries led the World Health Organization to declare a public health emergency of international concern.3
What You Need To Know
The NIH’s STOMP trial found that tecovirimat, though safe, did not improve lesion resolution or pain relief in patients with mild to moderate mpox.
Tecovirimat remains available through the CDC’s expanded access program for eligible patients, including those with severe immunocompromise.
Ongoing research continues to explore tecovirimat’s potential role in treating severe mpox cases, especially for individuals with compromised immune systems.
Additional analysis at the DSMB’s request indicated that there was less than a 1% chance the study would show tecovirimat’s efficacy if completed. The study reported that adverse events were low and similar between the tecovirimat and placebo groups.1
Despite the lack of efficacy observed in this trial, researchers are continuing to investigate the role of tecovirimat in treating individuals with severe or at-risk cases of mpox, particularly those with compromised immune systems. The CDC has an expanded access program for treating severe cases of mpox, and tecovirimat remains available to eligible patients outside of clinical trials.1
In addition to this trial, similar studies of tecovirimat are being conducted, including a study in the Democratic Republic of the Congo, where a clade I outbreak has occurred. The findings from these studies will continue to inform treatment protocols and potential future therapies for mpox.1
Timothy Wilkin, MD, MPH chair of the STOMP study, emphasized the value of the trial despite its negative results. “STOMP has been a model for global collaboration and for quickly providing critical scientific data during an outbreak,” he said.1
The CDC’s EA-IND protocol also allows for tecovirimat’s use under the Public Readiness and Emergency Preparedness (PREP) Act, providing liability protection for healthcare providers and compensation for patients. Further clinical trials are needed to assess the drug’s role in treating severe mpox cases, especially for patients with advanced HIV or other severe immunocompromising conditions.2
