Smallpox therapy tecovirimat not efficacious in treating clade II mpox  

1. In this phase 3, randomized, placebo-controlled trial, an antiviral medication approved for treating smallpox (tecovirimat) did not accelerate clinical resolution of mpox compared to placebo. 

2. Tecovirimat also did not reduce pain levels or lead to increased viral DNA clearance compared to placebo. 

Evidence Rating Level: 1 (Excellent)

Study Rundown: In recent years, multiple strains of the human mpox virus (hMPXV) have caused widespread infections across numerous countries where it previously was not endemic. Although the overall mortality rate is low, immunocompromised individuals are at higher risk for complications including ocular and skin lesions. Tecovirimat is an FDA-approved treatment for smallpox which has also shown activity against hMPXV in preclinical studies. This randomized clinical trial was conducted to assess the efficacy of tecovirimat treatment in adults with clade II mpox. It was found that there was no significant difference in healing of skin or mucosal lesions between the tecovirimat group and the placebo group. Further, there were no substantial between-group differences in pain reduction among those with severe pain, in viral DNA clearance, or in the rate of adverse events. This study had a number of strengths, including a large international study population and the analysis of both objective and participant-reported measures of clinical resolution. Key limitations were a lack of dose escalation assessment and exclusion of immunosuppressed patients from direct comparisons with placebo. Overall, this study showed no evidence for the efficacy of tecovirimat in treating clade II mpox.

Click to read the study in NEJM

Relevant Reading: Tecovirimat Use under Expanded Access to Treat Mpox in the United States, 2022–2023

In-Depth [randomized controlled trial]: In this phase 3, multicenter, double-blind, randomized controlled trial, 412 adults with clade II hMPXV were randomly assigned in a 2:1 ratio to receive a two-week course of either tecovirimat or placebo. Those with laboratory confirmation of mpox and active skin or mucosal lesions were included for analysis. The primary outcome was clinical resolution, defined as healing of all skin and visible mucosal lesions. Secondary outcomes of interest were pain reduction, viral DNA clearance, and safety.  By day 29, a total of 177 of 225 participants (79%) in the tecovirimat group and 90 of 111 (81%) in the placebo group had clinical resolution of lesions, with a competing-risks hazard ratio for resolution of .98 (95% confidence interval [CI], 0.74 to 1.31; p=0.89). The two groups had a similar median pain score at baseline, and the mean time-weighted average reduction in pain from baseline was 1.6 in tecovirimat and 1.7 in placebo group (difference in means, -0.1 point; 95% CI, -0.6 to 0.5). There was no difference between groups in proportion of samples with undetectable hMPXV DNA (82% versus 80%), or in the incidence of adverse events grade 3 or higher (difference, 1 percentage point; 95% CI, -5 to 5). These findings were consistent in subgroup analyses of patients with positive HIV or prior mpox vaccination. Overall, tecovirimat did not show greater efficacy in treating mpox as compared to placebo by any prespecified metric. 

Image: PD

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