Tecovirimat for Clade I MPXV Infection in the Democratic Republic of Congo
Authors: Rosine Ali, Jules Alonga, Jean-Luc Biampata, Michael Kombozi Basika, Irina Maljkovic Berry, Nella Bisento, Emily Blum, Tyler Bonnett, Katherine Cone, Ian Crozier, Richard Davey, Ali Dilu, Lori E Dodd, Iman Gulati, Dennis Hruby, Augustin Ibanda, Francis Isse, Sylva Sivasingana Kasareka, Gaby Kayembe, Richard Kojan, Esaie Kindombe Luzolo, H Clifford Lane, Leader Lawanga, Laurens Liesenborghs, Claude Shosongo Lunghe, Yves Lula, Mariano Lusakibanza, Gaston Tona Lutete, Placide Mbala-Kingebeni, Alejandra Miranda, Daniel Mukadi-Bamuleka, Gael Mukendi, Patrick Mutombo Lupola, Jean-Jacques Muyembe-Tamfum, Robin Ndungunu, Bruce Nganga, Nsengi Ntamabyaliro, Veronique Nussenblatt, Imoite Omulepu, John Omalokoho Onosomba, Michael Proschan, Kevin Rubenstein, Inga Saknite, Adam Schechner, Kathryn Shaw-Saliba, Billy Sivahera, Mary Smolskis, Amy Tillman, Eric Tkaczyk, Celestin Tshimanga, Olivier Tshiani Mbaya, Antoine Tshomba, Freddy Yemba Unda Tshomba, David Vallee, Susan Vogel, Shera Weyers
Journal: New England Journal of Medicine (2025)

Tecovirimat is available for the treatment of mpox (formerly known as monkeypox) in Europe and the United States, on the basis of findings from efficacy studies in animals and safety evaluations in healthy humans. Evidence from randomized, controlled trials of safety and efficacy in patients with mpox is lacking. We conducted a double-blind, randomized, placebo-controlled trial of tecovirimat in patients with mpox in the Democratic Republic of Congo (DRC). Patients with at least one mpox skin lesion and positive polymerase-chain-reaction results for clade I MPXV were assigned in a 1:1 ratio to receive tecovirimat or placebo. All patients received supportive care. The primary end point was resolution of mpox lesions, measured in number of days after randomization. Safety was also assessed. From October 7, 2022, through July 9, 2024, a total of 597 patients underwent randomization - 295 to receive tecovirimat and 302 to receive placebo. The median time from randomization to lesion resolution was 7 days with tecovirimat and 8 days with placebo; the competing-risks hazard ratio for lesion resolution was 1.13 (95% confidence interval [CI], 0.97 to 1.31; P = 0.14). Results were similar whether patients began the trial regimen within 7 days after the reported onset of symptoms (competing-risks hazard ratio, 1.16; 95% CI, 0.98 to 1.37) or more than 7 days after onset (competing-risks hazard ratio, 1.00; 95% CI, 0.71 to 1.40). Overall mortality was 1.7%, which was lower than the case fatality rate of 4.6% reported in the DRC in 2023. At 14 days, the percentages of patients who had blood, lesion, and oropharyngeal samples negative for MPXV by PCR were similar in the two groups. Adverse events occurred in 72.9% of the patients in the tecovirimat group and 70.5% of those in the placebo group, and serious adverse events were reported in 5.1% and 5.0%, respectively. Tecovirimat did not reduce the number of days to lesion resolution in patients with mpox caused by clade I MPXV. No safety concerns were identified. (Funded by the National Institute of Allergy and Infectious Diseases and others; PALM007 ClinicalTrials.gov number, NCT05559099.).