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Brincidofovir a very-broad-spectrum antiviral drug?

October 9, 2014

Brincidofovir, or CMX001, is a broad-spectrum antiviral drug in development by Chimerix. The drug is presently in Phase 3 trials for life-threatening adenovirus in children and adults who have compromised immune systems and for adults with cytomegalovirus infections acquired after hematopoietic stem cells transplants for cancer.

Brincidofovir is a relative of a drug called Cidofovir, an antiviral sold by Gilead as Vistide, which is given intravenously. This requires some medical expertise since it’s not active by mouth. It has to be prepared in solution that is less stable in storage than a pill, and more prone to degradation. It is also extremely unforgiving to the kidneys and cannot be used on someone with renal failure.

In the late 1990′s Karl Hostetler, MD, then at the University of California at San Diego and his team came up with several chemical analogues of Cidofovir intended to be active orally, more potent against viruses, and spare the kidney of any damage. Brincidofovir was the result of that work.

In early September, representatives of Chimerix and several other companies met at WHO headquarters in Geneva to discuss the current development status of drugs and vaccines against the current Ebola outbreak in West Africa. The day before the meeting began Chimerix announced that researchers at the Centers for Disease Control and Prevention (CDC) and the National Institutes of Health (NIH) found that Bincidofovir had activity against Ebola virus infection of cultured cells.

Brincidofovir has shown efficacy in humans against DNA viruses. But Ebola is not a DNA virus. Its genome is made of RNA and the virus uses a very different enzyme to make more copies to create more viruses.

Brincidofovir’s inhibition of Ebola virus in vitro doesn’t make complete sense based on what we know about the drug’s mechanism against a bioterror agent like smallpox or other pathogenic viruses such as adenovirus and CMV. We also don’t know if it works in animals infected with Ebola – a bar that has already been met by several other drugs such as Tekmira’s TKM-Ebola, Sarepta’s AVI-7537, and ZMapp antibody cocktail.

Unlike those other drugs, brincidofovir has already been used in at least 1,000 human subjects. The drug has even been given extensively in children. Indicating how brincidofovir behaves in the body of not just healthy humans, but very ill humans.

And while, yes, brincidofovir had been under development for DNA viruses, the unpublished CDC/NIH data suggest it works against the RNA-based Ebola virus, at least in cultured cells. Some cancer chemotherapy drugs based on the building blocks of DNA and RNA, like brincidofovir, are known to inhibit both DNA and RNA synthesis in human cells. So we may learn that brincidofovir is a very-broad-spectrum antiviral drug.

The Ebola infection slowly destroys the functioning of the major organs of the body, especially the liver and kidney. Brincidofovir can be used in patients with very damaged kidneys.

So while it may seem that Brincidofovir is moving into Ebola-infected humans with only cell culture studies justifying its potential use, its overall package is stronger in many respects than other drugs that have received more press.

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