The metabolism of the drug is as such: once the drug enters the target infected cell, Brincidofovirs phosphodiester bond is then hydrolyzed to generate cidofovir which is then phosphorylated to the active cidofovir diphosphate. The volume of distribution of the drug is 1230 L. Brincidofovir is almost entirely absorbed in plasma. History
Because smallpox is eradicated, the effectiveness of brincidofovir was studied in animals infected with viruses that are closely related to the variola virus. Effectiveness was determined by measuring animals survival at the end of the studies.Safety information to support approval of brincidofovir was derived from clinical trials of the drug for a non-smallpox indication, primarily from patients who received hematopoietic stem cell transplants.The U.S. Food and Drug Administration (FDA) granted the application for brincidofovir priority review, fast track, and orphan drug designations. The FDA approved brincidofovir under the agencys Animal Rule, which allows findings from adequate and well-controlled animal efficacy studies to serve as the basis of an approval when it is not feasible or ethical to conduct efficacy trials in humans. Ethical considerations
Brincidofovir (CMX001) was the subject of widespread social media campaigning in 2014, which was then picked up by national news sources about a boy with an adenovirus infection following a bone marrow transplant. The family requested legal access to the still-unapproved drug outside of any clinical trial, and Chimerix initially denied the request. After a short and intense media campaign, Chimerix got permission from the FDA to start a limited open-label trial which allowed the boy to receive the drug.
Brincidofovir, sold under the brand name Tembexa, is an antiviral drug used to treat smallpox. Brincidofovir is a prodrug of cidofovir. Conjugated to a lipid, the compound is designed to release cidofovir intracellularly, allowing for higher intracellular and lower plasma concentrations of cidofovir, effectively increasing its activity against dsDNA viruses, as well as oral bioavailability.The most common side effects include diarrhea, nausea, vomiting, and abdominal pain.Brincidofovir was approved for medical use in the United States in June 2021. Medical uses
Brincidofovir is indicated for the treatment of human smallpox disease caused by variola virus. Mechanism of Action
Brincidofovir is a pro-drug that is composed of cidofovir, conjugated with a lipid molecule. The lipid aspect of the molecule takes on the action of endogenous lysopghosphatidyl choline, which then is able to enter cells in the body which are infected with smallpox. Once the infected cell takes in the drug, the drug cleaves to generate cidofovir. Cidofovir is then consequently phosphorylated to yield Cidofovir Diphosphate, which is the active drug.Cidofovir diphosphate arises from two key mechanisms. Firstly, cidofovir diphosphate inhibits the variola viruss DNA-polymerase mediated DNA synthesis.The second mechanism is that the drug acts as an acyclic nucleotide and incorporates itself into the viral DNA chain, which then stops viral DNA synthesis. Pharmacokinetics
The oral bioavailability of Brincidofovir is 13.4% as a tablet and 16.8% in a suspension.