Tecovirimat Fails to Show Efficacy Against Mpox in Landmark STOMP Trial
Key Insights
The international STOMP trial found that tecovirimat, an FDA-approved smallpox (search) treatment, did not improve clinical resolution or reduce pain in adults with clade II mpox (search) compared to placebo.
The phase 3 randomized controlled trial enrolled 412 participants across seven countries, with clinical resolution rates of 79% for tecovirimat versus 81% for placebo by day 29.
Results published in the New England Journal of Medicine highlight the urgent need for new therapeutic approaches to treat mpox (search) and other orthopoxviruses (search).
The highly anticipated STOMP trial has delivered disappointing results for tecovirimat, revealing that the antiviral drug does not provide significant clinical benefits for adults with clade II mpox (search) infection. The international phase 3 study, published in the New England Journal of Medicine, challenges widespread expectations about the drug's therapeutic potential and underscores the critical need for alternative treatment approaches.
Trial Design and Participants
STOMP (Study of Tecovirimat for Mpox (search)) was a randomized, placebo-controlled, double-blind trial that enrolled 412 eligible participants across 49 sites in seven countries, including the United States, Peru, Mexico, Thailand, Argentina, Japan, and Brazil. The study launched in September 2022 in response to the global mpox outbreak characterized by increased person-to-person transmission.
Participants were randomized to receive either tecovirimat (600 mg) or placebo twice daily for 14 days. The study population broadly represented those most affected by the 2022-2023 outbreak, with a median age of 34 years, 99% male participants, and 35% living with HIV (search) among those with known status. Additionally, 23% had received at least one dose of an mpox (search) vaccine.
Primary Efficacy Results
The trial's primary endpoint measured time to clinical resolution, defined as the first day all skin lesions were scabbed or healed and visible mucosal lesions were healed. By day 29, clinical resolution rates were virtually identical between groups: 79% in the tecovirimat arm compared to 81% in the placebo group.
The lack of efficacy extended beyond lesion resolution. Tecovirimat showed no significant impact on pain reduction among participants with severe pain, with differences of only 0.1 point on a 10-point scale. The drug also failed to accelerate complete lesion healing or enhance viral DNA clearance compared to placebo.
Safety Profile
Despite its lack of efficacy, tecovirimat demonstrated a favorable safety profile. Adverse events of grade 3 or higher occurred in only 4% of the treatment group, with overall adverse event rates similar between the tecovirimat and placebo arms. This confirms that while the drug is well-tolerated, it does not offer therapeutic advantages for typical clade II mpox (search) cases.
Clinical Implications
"This publication reminds us of the importance of randomized clinical trials – tecovirimat was widely expected by the scientific community to be an effective treatment for mpox (search) and it was only through STOMP that we were able to conclusively demonstrate that it is not," said ACTG (search) Chair Joseph J. Eron, M.D., from the University of North Carolina.
The FDA had previously approved tecovirimat for smallpox (search) treatment based on animal model data, as smallpox has been eradicated and human trials were not feasible. However, the STOMP results demonstrate that efficacy against one orthopoxvirus does not guarantee effectiveness against another.
Protocol Chair Timothy Wilkin, M.D., M.P.H., from the University of California San Diego, noted that "while the results may not be what the community had hoped for, they provide important insights into our understanding of mpox (search) and its treatment and encourage us to continue looking for a safe and effective treatment."
Future Directions
The trial stopped enrolling participants in December 2024 after an interim analysis confirmed the lack of treatment benefit. These findings highlight the urgent need to conduct randomized controlled trials to identify safe and effective therapeutics for mpox (search) and other orthopoxviruses (search), particularly as mpox continues to pose global health challenges.
For clinicians managing mpox (search) patients, the results suggest that supportive care and pain management should remain the primary focus for patients with mild to moderate disease, ensuring better resource allocation during outbreaks while the search for effective treatments continues.