Tecovirimat Found Ineffective in Treating Clade II Mpox in NIH-Sponsored Study

A clinical trial funded by the National Institutes of Health (NIH) has found that tecovirimat, an antiviral drug, does not expedite the resolution of clade II mpox lesions or significantly improve pain management. The international study, which began in 2022, was halted in late 2024 after interim findings showed that the drug, when used alone, was ineffective. Detailed results were presented at the 2025 Conference on Retroviruses and Opportunistic Infections (CROI) in San Francisco.

Mpox, a viral infection spread through close contact, has two primary clades, with clade II responsible for a 2022 global outbreak. While the virus continues to circulate at low levels, a separate outbreak of clade I mpox in Central and East Africa was declared a public health emergency in 2024. Tecovirimat, also known as TPOXX, was approved by the Food and Drug Administration (FDA) for treating smallpox based on animal studies but had not been tested in humans for mpox before this study.

The Study of Tecovirimat for Mpox (STOMP) enrolled participants in the U.S., Puerto Rico, and several international locations, including Argentina, Brazil, Japan, Mexico, Peru, and Thailand. It was a randomized, placebo-controlled trial where neither participants nor investigators knew who received the drug or a placebo. Some participants—those who were immunocompromised, had severe mpox, or were pregnant—were assigned to an open-label arm and received tecovirimat directly. The study aimed to assess the safety of the drug and determine whether a 14-day course shortened symptom duration or improved pain relief.

By the 29th day of the study, 83% of participants who received tecovirimat had achieved clinical resolution, compared to 84% in the placebo group, showing no significant difference. Pain reduction was also similar between groups, with both experiencing a decrease in pain scores by about 3 points on an 11-point scale. While early viral DNA clearance appeared slightly more common in the tecovirimat group, this difference diminished by day 15 and was not statistically significant. Adverse event rates were comparable between groups.

A separate analysis of STOMP’s open-label arm found that younger participants and those without HIV—or those with HIV who were virally suppressed—tended to experience faster recovery. However, the study did not establish definitive factors influencing mpox disease progression. The findings aligned with results from a similar study, PALM007, conducted in the Democratic Republic of the Congo.

The trial was led by the NIH-funded AIDS Clinical Trials Group (ACTG), with tecovirimat supplied by SIGA Technologies, Inc. Results will be published in a scientific journal. More information is available at ClinicalTrials.gov under identifier NCT05534984.

Article by multiple RFHC contributors, based upon information from the National Institute of Allergy and Infectious Diseases (NIAID).

---