A clinical trial testing a smallpox antiviral for mpox was halted after interim findings showed no efficacy in reducing lesion resolution or pain in mild to moderate cases.
RT’s Three Key Takeaways:
- No Efficacy in Mpox Treatment: The smallpox antiviral drug being tested showed no significant effect on lesion resolution or pain reduction in mild to moderate mpox cases.
- Enrollment Halted: Based on interim findings and a low likelihood of demonstrating efficacy, the trial’s enrollment was stopped for both randomized and open-label study arms.
- No Safety Concerns: The investigational drug was found to have a comparable safety profile to placebo, with low adverse events reported during the study.
The antiviral drug tecovirimat—approved by the Food and Drug Administration to treat smallpox—did not reduce the time to lesion resolution or have an effect on pain among adults with mild to moderate clade II mpox and a low risk of developing severe disease, according to an interim data analysis from an international clinical trial called the Study of Tecovirimat for Mpox (STOMP).
There were no safety concerns associated with tecovirimat.
Considering these findings, the study’s Data Safety and Monitoring Board (DSMB) recommended stopping further enrollment of participants who were being randomized to tecovirimat or placebo. As the study sponsor, the National Institutes of Health’s (NIH) National Institute of Allergy and Infectious Diseases (NIAID) accepted the DSMB’s recommendation.
Given the lack of an efficacy signal, NIAID also closed enrollment into an open-label study arm for participants with or at elevated risk of severe disease that was not designed to estimate the drug’s efficacy.
“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,” says NIAID director Jeanne Marrazzo, MD, MPH, in a release. “Before 2022, no treatment candidate had been studied in people with mpox, and this trial is a critical step in our systematic evaluation of existing antivirals like tecovirimat while pursuing novel antivirals and antibody-based mpox therapeutics.”
Understanding the Mpox Risk Landscape
Mpox is caused by a virus that spreads mainly through close contact. Two types of the virus have been identified, referred to as clades I and II, historically present in Central and West Africa, respectively. A clade II subtype virus caused a global mpox outbreak 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 by the World Health Organization. Travel-related cases of clade I mpox have been reported internationally and the first reported case in the United States was diagnosed on Nov 15. In the United States, the risk of clade I mpox to the public remains low. People with significantly compromised immune systems or certain preexisting skin conditions, children, and individuals who are pregnant have an elevated risk of developing severe mpox.
Tecovirimat, also known as TPOXX, was initially approved to treat smallpox—a virus closely related to, but far more serious than, the virus that causes mpox—but the drug’s safety and efficacy as an mpox treatment have not been established prior to this year.
The STOMP study began in September 2022 as part of the US whole-of-government response to the clade II mpox outbreak. The randomized international efficacy study 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 were randomized at a two-to-one ratio to receive tecovirimat or a placebo.
Study Design and Interim Analysis
Randomized participants and investigators were blinded, meaning they did not know who received tecovirimat or placebo. Children, pregnant people, and other participants with severe disease, certain skin conditions, or substantially suppressed immune systems were assigned to an open-label study arm, meaning they all received tecovirimat instead of being randomized.
The STOMP study assessed all participants’ safety and, in randomized arms, evaluated whether a 14-day course of tecovirimat reduced the time to clinical resolution of visible mpox lesions and improved other outcome measures like pain, compared to a placebo.
A planned interim analysis at 75% of the study’s target enrollment showed there was no difference in the time to lesion resolution between participants treated with tecovirimat compared with those who received a placebo. Pain decreased similarly between participants treated with tecovirimat and those who received a placebo.
Final Steps and Further Analysis
At the DSMB’s request, an additional assessment was performed and showed that there was a less than 1% chance that the study would show tecovirimat to be effective if it were to complete enrollment and follow-up, based on the study design and available data. At the time of analysis, reported adverse events were low and comparable between tecovirimat and placebo.
By design, the open-label study arm did not assign participants to receive a placebo, so STOMP will not draw conclusions about the efficacy of tecovirimat in participants with, or at elevated risk for, severe clade II mpox.
Further analyses of the study data are ongoing. Study participants are being notified of the findings, and study clinicians will make individual clinical care plans with participants based on their disease severity and symptoms. The Centers for Disease Control and Prevention holds an expanded access investigational new drug protocol for mpox treatment outside of research settings. Eligible persons include those with severe immunocompromise, including people with advanced HIV, for whom the role of tecovirimat treatment has not been fully established through a clinical trial.
Photo caption: Colorized transmission electron micrograph of two particles of the virus that causes mpox, cultivated and purified from cell culture.
Photo credit: NIAID