Researchers from seven different countries recently completed a large, prospective, double-blind, placebo-controlled trial to determine the efficacy of tecovirimat for the treatment of mpox (Zucker J, Fisher WA, Zheng L. Tecovirimat for the Treatment of Mpox. N Engl J Med. 2026 Feb 26;394(9):884-895). Tecovirimat has been approved for the treatment of smallpox under the U.S. Food and Drug Administration (FDA) Animal Rule based on proven efficacy in a nonhuman primate model. Tecovirimat targets the envelope protein, which is conserved across orthopoxviruses, such as mpox, and is essential for the formation of extracellular viral particles.
Subjects with skin or mucosal mpox lesions were randomized to receive either tecovirimat or placebo in a 2:1 ratio for 14 days — 275 in the tecovirimat group and 137 in the placebo group. The primary outcome was resolution of lesions. The estimated cumulative incidence of clinical resolution was 83% with tecovirimat and 84% with placebo.
The authors concluded that, “This trial showed no evidence that tecovirimat therapy shortened the time to clinical resolution, reduced pain, or increased viral clearance among adults with clade II mpox…these findings highlight the need to identify safe and effective therapeutics for mpox and other orthopoxviruses.”
Contributed by: Paul A. Offit, MD
Researchers from seven different countries recently completed a large, prospective, double-blind, placebo-controlled trial to determine the efficacy of tecovirimat for the treatment of mpox (Zucker J, Fisher WA, Zheng L. Tecovirimat for the Treatment of Mpox. N Engl J Med. 2026 Feb 26;394(9):884-895). Tecovirimat has been approved for the treatment of smallpox under the U.S. Food and Drug Administration (FDA) Animal Rule based on proven efficacy in a nonhuman primate model. Tecovirimat targets the envelope protein, which is conserved across orthopoxviruses, such as mpox, and is essential for the formation of extracellular viral particles.
Subjects with skin or mucosal mpox lesions were randomized to receive either tecovirimat or placebo in a 2:1 ratio for 14 days — 275 in the tecovirimat group and 137 in the placebo group. The primary outcome was resolution of lesions. The estimated cumulative incidence of clinical resolution was 83% with tecovirimat and 84% with placebo.
The authors concluded that, “This trial showed no evidence that tecovirimat therapy shortened the time to clinical resolution, reduced pain, or increased viral clearance among adults with clade II mpox…these findings highlight the need to identify safe and effective therapeutics for mpox and other orthopoxviruses.”
Contributed by: Paul A. Offit, MD