Brincidofovir

Background: Brincidofovir is an oral antiviral drug used in the treatment of human smallpox infections. It is a lipid conjugate pro-drug of the acyclic nucleotide analogue cidofovir - this lipid conjugate improves drug delivery to the target cells and significantly reduces the nephrotoxicity typically associated with cidofovir therapy. Due to its formulation as a pro-drug brincidofovir also carries a greater bioavailability than cidofovir, allowing for oral administration rather than intravenous. Cidofovir itself has broad antiviral activity against several DNA viruses, resulting in brincidofovir being investigated for the prevention and treatment of cytomegalovirus (CMV), BK Virus (BKV), adenoviruses (AdV), and Epstein-Barr virus (EBV), amongst others.

Brincidofovir, developed by Chimerix under the brand name Tembexa, was approved by the FDA for the treatment of smallpox infection in June 2021. As smallpox has been eradicated, the efficacy of Tembexa was assessed in animals infected with viruses closely related to variola. The approval was granted under the agency’s Animal Rule, which allows for a drug to be approved based on the results of well-controlled animal studies when human trials would be unethical or infeasible.