Evaluating Tecovirimat in Hospitalized Patients With Monkeypox
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Reviewed by Dat Tien Nguyen, B.A, ScM.
Translated by Nhi Phuong Quynh Le, B.A |
Posted on May 14th, 2025
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Since its global spread during the 2022 outbreak, monkeypox has been effectively controlled in most parts of the world. However, cases have continued to rise in sub-Saharan Africa, particularly in the Democratic Republic of Congo (DRC). Currently, there is no approved specific antiviral treatment for monkeypox. In response to the growing burden, the United States National Institute of Allergy and Infectious Diseases (NIAID) partnered with the Congolese Ministry of Health to investigate the efficacy of tecovirimat as a treatment for monkeypox infection.
The clinical trial was conducted between October 2022 and July 2024 in two provinces of the DRC. It enrolled 597 hospitalized patients who were receiving standard supportive care, including symptom relief, nutritional support, skincare, and oropharyngeal hygiene. The median age of participants was approximately 12 years, and enrollment occurred an average of six days after symptom onset. Patients presented with an average of 500 lesions, and approximately 40% met the World Health Organization’s criteria for severe disease, defined as having more than 250 lesions. At baseline, clade I monkeypox virus (MPXV) DNA was detected in the lesions of over 95% of patients and in 86% of oropharyngeal swabs. Viremia was present in 54% of cases. Only 4% of participants had received prior smallpox vaccination. Given the importance of nutritional status for drug absorption, dietary support ensured a minimum intake of 600 kilocalories per day, which was particularly relevant as 18% of participants were malnourished.
In addition to standard care, participants were randomized to receive either oral tecovirimat or a placebo. Tecovirimat, originally developed for smallpox, is now being investigated for its effectiveness against other orthopoxviruses such as monkeypox and rabbitpox. The drug acts by binding to the viral VP37 envelope protein, thereby disrupting the formation of mature virions and blocking further transmission. Treatment was continued until lesion resolution. However, the study found that tecovirimat did not significantly reduce the duration of symptoms or hasten virological clearance by day 14 compared to placebo. Notably, the case fatality rate among study participants was 1.7%, markedly lower than the national average of 4.6%. This reduction in mortality is likely attributable to the comprehensive inpatient care and nutritional support provided. The authors emphasized the need for further research to optimize tecovirimat dosing, as current guidelines are based primarily on animal models and pharmacokinetic data from healthy volunteers.
The clinical trial was conducted between October 2022 and July 2024 in two provinces of the DRC. It enrolled 597 hospitalized patients who were receiving standard supportive care, including symptom relief, nutritional support, skincare, and oropharyngeal hygiene. The median age of participants was approximately 12 years, and enrollment occurred an average of six days after symptom onset. Patients presented with an average of 500 lesions, and approximately 40% met the World Health Organization’s criteria for severe disease, defined as having more than 250 lesions. At baseline, clade I monkeypox virus (MPXV) DNA was detected in the lesions of over 95% of patients and in 86% of oropharyngeal swabs. Viremia was present in 54% of cases. Only 4% of participants had received prior smallpox vaccination. Given the importance of nutritional status for drug absorption, dietary support ensured a minimum intake of 600 kilocalories per day, which was particularly relevant as 18% of participants were malnourished.
In addition to standard care, participants were randomized to receive either oral tecovirimat or a placebo. Tecovirimat, originally developed for smallpox, is now being investigated for its effectiveness against other orthopoxviruses such as monkeypox and rabbitpox. The drug acts by binding to the viral VP37 envelope protein, thereby disrupting the formation of mature virions and blocking further transmission. Treatment was continued until lesion resolution. However, the study found that tecovirimat did not significantly reduce the duration of symptoms or hasten virological clearance by day 14 compared to placebo. Notably, the case fatality rate among study participants was 1.7%, markedly lower than the national average of 4.6%. This reduction in mortality is likely attributable to the comprehensive inpatient care and nutritional support provided. The authors emphasized the need for further research to optimize tecovirimat dosing, as current guidelines are based primarily on animal models and pharmacokinetic data from healthy volunteers.