The antiviral drug tecovirimat (Tpoxx) is no better than placebo in achieving a shorter time to clinical resolution, reduced pain, or increased viral DNA clearance in adults infected with clade 2 mpox virus, per a phase 3 randomized controlled trial published yesterday in the New England Journal of Medicine.
An international roster of investigators in the Advancing Clinical Therapeutics Globally Study of Tecovirimat for Human Mpox Virus (STOMP/A5418) group randomly assigned 412 participants in a 2:1 ratio to receive either tecovirimat (275 patients) or a placebo (137) for 14 days from September 2022 to October 2024.
Clade 2 carries up to 7% fatality rate
Recent public health emergencies of international concern have been declared for both clade 2 mpox virus, which has caused more than 100,000 infections and 220 deaths in more than 100 countries where mpox has historically not been endemic, and clade 1b mpox, which is tied to more severe illness and increased transmissibility, the study authors noted.
“Although the overall mortality rate of clade II mpox is low, persons with immunosuppression have higher morbidity and case fatality rates of up to 7%,” they wrote. “Many of these persons also have severe symptoms and a prolonged time to lesion healing, which can lead to isolation for extended periods.”
Tecovirimat is approved for smallpox treatment under the Food and Drug Administration Animal Rule based on its effectiveness in nonhuman primate models of mpox, but the clinical efficacy of tecovirimat against human clade 2 mpox has been unclear.
34% reported severe pain at baseline
Of the 412 participants, 344 had confirmed mpox, and 336 had active skin or mucosal lesions. The median participant age was 34 years, 99% were men, and 44% were Hispanic. A total of 35% of participants reported proctitis (inflammation of the rectum’s inner lining), and 34% reported severe pain. Of 337 participants with known HIV status, 35% had HIV. In total, 23% had received at least one lifetime dose of smallpox or mpox vaccine.
The protocol included a separate open-label group that enrolled participants who had or were at high risk for severe mpox, including children, pregnant or breastfeeding women, and those with high immunosuppression or eye or high-risk skin lesions.
At six days, participants who had severe mpox or severe pain could discontinue blinded tecovirimat or placebo and start a 14-day course of open-label tecovirimat, with the initial trial-group assignment staying blinded.
“This rescue strategy, which allowed both placebo and tecovirimat recipients to switch to open-label tecovirimat, was necessary to preserve blinding and because tecovirimat was the only widely available therapeutic option at the time that was considered to be safe,” the researchers wrote.
The trial was conducted at 49 sites in Argentina, Brazil, Japan, Mexico, Peru, Thailand, and the United States.
Continued search for safe, effective therapies
At 29 days, the estimated cumulative rate of clinical resolution was 83% in tecovirimat recipients and 84% in those given placebo, and 79% of tecovirimat recipients and 81% in the placebo group had clinical resolution of skin lesions. The competing-risks hazard ratio (crHR) for clinical resolution was 0.98. No significant differences were observed between the two groups in pain reduction in participants reporting severe pain (difference, 0.1 point) or in complete lesion healing (crHR, 0.97).
