Brincidofovir (Tembexa®): A Comprehensive Monograph on a Novel Antiviral Agent for Orthopoxvirus Infections and Beyond

Executive Summary

Brincidofovir represents a significant advancement in antiviral therapy, embodying the principles of rational drug design to address the limitations of a preceding compound. It is a lipid-conjugated prodrug of cidofovir, a modification strategically engineered to enhance oral bioavailability, increase intracellular drug concentrations, and mitigate the dose-limiting nephrotoxicity associated with its parent molecule. This design has led to a bifurcated and complex developmental history, culminating in both a landmark public health achievement and a series of significant clinical challenges.

The primary success of brincidofovir, marketed as Tembexa®, is its approval by the United States Food and Drug Administration (FDA) as a medical countermeasure for the treatment of smallpox. This approval was a notable regulatory milestone, achieved through the FDA's Animal Rule, which permits efficacy data from appropriate animal models when human trials are unethical or infeasible. As a component of the U.S. Strategic National Stockpile, brincidofovir serves as a critical asset in national biodefense preparedness, offering an orally administered antiviral effective against orthopoxviruses for all age groups, including neonates.