The Food and Drug Administration (FDA) has approved Tembexa® (brincidofovir) for the treatment of human smallpox disease in adult and pediatric patients, including neonates.
Tembexa, an orthopoxvirus nucleotide analogue DNA polymerase inhibitor, was developed as a medical countermeasure against concerns that the variola virus could be used as a bioweapon. The treatment was approved under the FDA’s Animal Rule which allows findings from animal efficacy studies to determine the approval for a drug when feasible or ethical studies in humans cannot be conducted.
The approval was based on efficacy data in adequate and well-controlled animal studies using a rabbitpox model (New Zealand White rabbits infected with rabbitpox virus) and a mousepox model (BALB/c mice infected with ectromelia virus). Findings showed that treatment with brincidofovir resulted in a statistically significant improvement in survival compared with placebo, except when the 10/5/5mg/kg regimen was initiated at day 6 post-challenge in the mousepox study.
The safety of brincidofovir was supported by data from phase 2 and 3 trials investigating the drug for a non-smallpox indication, primarily in patients who received hematopoietic stem cell transplants. The most common adverse reactions were diarrhea, nausea, vomiting, and abdominal pain.
The Tembexa prescribing information includes a Boxed Warning regarding an increased risk for mortality when used for a duration longer than the recommended dosage. The drug is also considered a potential human carcinogen; direct contact with broken or crushed tablets or oral suspension should be avoided.
Tembexa is supplied as 100mg tablets in a 4-count blister card and as a 10mg/mL oral suspension in a 65mL bottle.
- FDA approves drug to treat smallpox. [press release]. Silver Springs, MD: US Food and Drug Administration; June 4, 2021.