US FDA approves Tembexa: the first smallpox antiviral drug for all ages

Chimerix recently announced that the US Food and Drug Administration (FDA) has approved Tembexa (brincidofovir) tablets and oral suspensions for the treatment of smallpox
.

Tembexa is suitable for adult and pediatric patients, including newborns

Tembexa is a lipid conjugate of nucleotide analogues, designed to simulate natural monoacyl phospholipids to achieve an effective intracellular concentration of antiviral active metabolite cidofovir diphosphate (cidofovir diphosphate)
.

Cidofovir diphosphate exerts its antiviral effect on orthopoxvirus by acting as an alternative substrate inhibitor for viral DNA polymerase-mediated synthesis of viral DNA

The FDA approval of Tembexa is based on the efficacy data of two lethal orthopox virus animal models of human smallpox disease, namely the rabbitpox model (New Zealand white rabbits infected with rabbitpox virus) and the mousepox model (BALB/c infected with mousepox virus) Mice)
.

In the key study of each model, when the animals were infected with a lethal virus dose and delayed treatment, compared with placebo, Tembexa treatment statistically significantly improved the survival rate

The FDA's "Animal Rules" allow testing of experimental drugs in animal models to support the effectiveness of diseases that are not ethical or suitable for human research
.

Tembexa's US prescribing information is accompanied by a black box warning that a longer course of treatment will increase the risk of mortality

Smallpox is a highly contagious disease caused by the smallpox virus
.

In history, smallpox has been epidemic many times and is one of the deadliest diseases, with a fatality rate of about 30%

Smallpox virus is one of the most complicated viruses, with double-stranded DNA genome, brick-shaped virus particles, and a very small amount of virus can cause infection
.

Smallpox virus is mainly transmitted through droplets and direct contact, and contaminated supplies can also be transmitted, with strong transmission capacity

The molecular structure of brincidofovir (picture source: Wikipedia)

The active pharmaceutical ingredient of Tembexa is brincidofovir, which is a nucleotide analogue that has antiviral activity against all five DNA virus families that affect humans, including adenovirus and variola virus, the latter can cause smallpox
.

Brincidofovir has high antiviral efficacy and high drug resistance barrier, no bone marrow suppression effect, and low risk of renal toxicity

brincidofovir uses Chimerix's lipid conjugation technology and compound library discovery with independent intellectual property rights
.

Previously, the FDA has granted brincidofovir Fast Track Status (FTD) and Orphan Drug Designation (ODD) for the treatment of smallpox

Since 2011, Chimerix has been working with the U.
S.
Biomedical Advanced Research and Development Administration (BARDA) to develop brincidofovir as a medical countermeasure against smallpox
.
In a variety of animal models of orthopoxvirus infection, brincidofovir has been shown to increase the survival rate of animals
.

Original source:

Chimerix Receives US Food and Drug Administration approval for TEMBEXA® (brincidofovir) for the Treatment of Smallpox