Background:
Tecovirimat is an FDA-approved oral antiviral medication for human smallpox and is being used widely for mpox treatment. The pharmacokinetics (PK) of tecovirimat has been assessed in animal models and healthy human volunteers, but data in people with mpox are limited.
Methods:
The Study of Tecovirimat for mpox (STOMP/ACTG 5418, NCT05534984) is an ongoing international randomized (2:1) clinical trial of the efficacy of tecovirimat for mpox. STOMP includes an open-label arm of participants with severe disease, immunosuppression, pregnancy and those aged <18 years, which is the focus of this report. Intensive PK assessments were conducted in a subset of participants on study day 8 (steady-state) following an observed dose of tecovirimat with a meal. All received 600 mg twice daily. Blood samples were collected pre-dose (time 0), 1, 2, 3, 4, 6, 8, and 10 hours post-dose. Tecovirimat concentrations were quantified by LC-MS/MS. PK were analyzed via noncompartmental analysis with predicted AUC0-12h and C12h determined from the terminal phase of the post-dose curve. AUC0-12h and C12h were compared to predicted exposures in fed healthy adults receiving the same doses (data from the U.S. FDA) and mean Cmin values associated with survival and clinical/virologic response in non-human primates (NHP) (minimum and maximum effective doses of 3 and 10 mg/kg/day, respectively).
Results:
PK data were generated in 13 participants (11 non-pregnant adults; 1 adolescent; 1 pregnant female adult). Of 12 non-pregnant participants, 11 were male, 5 were Black; 7 were persons with HIV of whom 4 had HIV-1 RNA <200 copies/mL, 2 were not on ART, and 2/6 had CD4 counts <200 cells/mm3; median (range) age and weight were 35 (<18-51) years and 77 (57-103) kg, respectively. Comparable PK was observed between non-pregnant participants and the pregnant participant and by HIV status (Table). Median tecovirimat AUC0-12h and C12h in non-pregnant adults were 38% and 72% lower than 50th percentile exposures in healthy adults. Despite lower tecovirimat exposures, C12h across all participants exceeded mean effective Cmin values in NHPs receiving 3 and 10 mg/kg/day.
Conclusions:
Persons with mpox had lower tecovirimat exposures vs. healthy adults, although concentrations remained above the minimally effective Cmin in NHPs. Future work will explore factors associated with tecovirimat PK and assess relationships with clinical and virologic outcomes to evaluate the clinical relevance of these PK differences.
