Tecovirimat fails to reduce clade II mpox lesions, pain, viral clearance
Key takeaways:
- The NIH stopped recruiting for trials of tecovirimat against mpox after the drug was deemed not significantly more effective vs. placebo.
- Other antivirals against mpox are under development, researchers said.
SAN FRANCISCO — Tecovirimat failed to reduce clade II mpox lesions, pain or viral clearance among participants in a study of the antiviral that was stopped early based on a futility analysis, according to data presented here.
“Tecovirimat did not lead to vast resolution of mpox skin lesions and did not improve pain control in those with clade II mpox,” Timothy Wilkin, MD, MPH, chief of the division of infectious diseases and global public health at the University of California, San Diego School of Medicine, said during a presentation at the Conference on Retroviruses and Opportunistic Infections. “We did find that tecovirimat was safe, [but it] did not lead to statistically significant reductions in mpox virus detection.”
The NIH launched the Study of Tecovirimat for Mpox (STOMP) trial in 2022 to assess whether the drug — which is approved in the United States for the treatment of smallpox — could be used to reduce the time to mpox resolution based on the initial analysis of small trials.
Wilkin, who led the STOMP trial, said during a briefing at the time that clinicians had already been using tecovirimat for months to treat mpox as the 2022 global clade II mpox outbreak spread and U.S. cases surpassed 25,000, despite a lack of data on the drug’s efficacy against the infection.
In the current study, the researchers assigned 412 adults (median age, 34 years; 98% men; 97% cisgender) who had symptomatic lab-confirmed or presumptive mpox for fewer than 14 days in a 2:1 ratio to receive either twice-daily oral tecovirimat 600 mg (n = 275) or placebo (n = 137) for 14 days. Among the participants, 33% were living with HIV and 22% had received at least one dose of mpox vaccine, according to the study abstract. The researchers excluded 68 participants without an mpox diagnosis from the analysis.
At baseline, the median symptom duration was 8 days (interquartile range [IQR], 5-10), median lesion number was nine (IQR, 4-19; maximum, 242) and 33% of participants reported severe pain, defined as a score of 7 to 10 on an 11-point scale.
By day 29, the cumulative incidence of clinical resolution was 83% for the tecovirimat group and 84% for the placebo group. Among the two groups, there was no difference in the receipt of open-label tecovirimat due to disease progression or persistent severe pain (7% for both). Adverse events (11% vs. 9%, respectively) and mean pain score reduction (3.2 vs. 3.1) were also similar between the two groups.
Finally, the researchers reported that more participants in the tecovirimat group had undetectable mpox DNA at day 8 (48% vs. 33%), but there was “no meaningful difference” at day 15 (83% vs. 78%).
The NIH stopped the study after an interim analysis of the data collected by Wilkin and colleagues, and the agency said the study data continue to be analyzed.
In August, the NIH announced that tecovirimat also did not reduce the duration of lesions among children and adults with clade I mpox, another strain of the virus that caused an outbreak in Eastern Africa last year.
Wilkin emphasized the need for more medications to treat mpox, noting that the drug brincidofovir — or perhaps a combination of brincidofovir and tecovirimat — should be explored. He also noted that there are monoclonal antibodies against mpox under development.
“We do have a lot of ongoing work about the pharmacokinetic and pharmacodynamic relationships [surrounding mpox], the emergence of resistance and the ability to culture viral samples,” Wilkin said. “But I think, in summary, our conclusion is that we really do need alternative agents for mpox treatment.”
References:
- ACTG. A5418: A randomized, placebo-controlled, double-blinded trial of the safety and efficacy of tecovirimat for the treatment of human mpox disease. https://actgnetwork.org/clinical-trial/a5418study-of-tecovirimat-for-human-monkeypox-virus-stomp/. Accessed March 14, 2025.
- CDC. Mpox: Clinical treatment of mpox. https://www.cdc.gov/mpox/hcp/clinical-care/index.html. Updated Jan. 30, 2025. Accessed March 14, 2025.
- CDC. Mpox: Tecovirimat (TPOXX) for treatment of mpox. https://www.cdc.gov/mpox/hcp/clinical-care/tecovirimat.html. Updated Feb. 6, 2025. Accessed March 14, 2025.
- NIH study finds tecovirimat was safe but did not improve mpox resolution or pain. https://www.nih.gov/news-events/news-releases/nih-study-finds-tecovirimat-was-safe-did-not-improve-mpox-resolution-or-pain. Published Dec. 10, 2024. Accessed March 14, 2025.
- Wilkin T, et al. Abstract 201. Presented at: Conference on Retroviruses and Opportunistic Infections; March 9-12, 2025; San Francisco.
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Wilkin T, et al. Abstract 201. Presented at: Conference on Retroviruses and Opportunistic Infections; March 9-12, 2025; San Francisco.
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