Biodefense

Chimerix is committed to completing development of a new antiviral therapy to treat smallpox in the event of an accidental outbreak or bioterror attack.

What is smallpox?

Smallpox is a highly contagious disease caused by variola virus. Smallpox is a very serious disease, causing fever and a distinctive, progressive skin rash; death occurs in approximately 30% of patients. Deaths attributable to smallpox during the 20th century have been estimated at 300–500 million.1 According to the CDC, the last documented case of smallpox occurred in 1977, and the disease has since been declared eradicated as the result of the smallpox vaccine.

If the disease is eradicated, what could cause a smallpox outbreak?

While smallpox is believed to be eradicated in nature, it is possible that variola virus could be used in a biological attack or be released accidentally. The U.S. Biomedical Advanced Research and Development Authority (BARDA) is dedicated to supporting the development and procurement of critical medical countermeasures to be used in the event of a smallpox outbreak.

Why is treatment necessary?

As a result of widespread vaccination, the last smallpox outbreak in the U.S. occurred in 1949. By 1972, the vaccine was no longer given routinely in the United States due to uncommon but serious side effects. As a result, most people born in the U.S. after 1972 have not been vaccinated against the disease and are vulnerable in the event of an outbreak. Vaccines are not effective once symptoms develop and these patients require antivirals.

The Chimerix Difference

Brincidofovir (BCV) is an oral antiviral designed to improve treatment of viral infections like smallpox by enhancing drug delivery to the intracellular site of viral replication. BCV effectively penetrates cells via its lipid conjugate technology, releasing the nucleotide analog cidofovir, which then acts to inhibit virus replication.

In 2011, Chimerix received a grant of $81 million from the U.S. Biomedical Advanced Research and Development Authority (BARDA) to continue exploring the development of BCV as a medical countermeasure to treat potential smallpox outbreaks in the event of a bioterror attack or accidental release.

The Chimerix smallpox animal efficacy development program is being conducted under the U.S. Food and Drug Administration’s Animal Efficacy Rule, which allows for testing of investigational drugs in animal models to support effectiveness in diseases that are not ethical or feasible to study in humans. Results from studies of BCV in both rabbit and mouse models of smallpox showed significant improvement in survival when compared to placebo, even when treatment was initiated late in the course of disease.

If successful, BCV will provide an important contribution to U.S. national security and public health preparedness for the treatment of smallpox. Current recommendations state there should be at least two smallpox antivirals with differing mechanisms of action on hand in the event of a smallpox outbreak.2 BCV is a compelling addition for smallpox as it complements existing countermeasures and adds a high barrier to resistance which could prove critical in the event of a bioterror attack. BCV is also being developed to treat pediatric populations. Antivirals such as BCV with oral bioavailability have an increased utility in an outbreak, increasing the ease of widespread use.

Read more about BCV.

Sources:

  1. Jarhrling, P., Fritz E., Hensley,L. (2005) Countermeasures to the Bioterrorist Threat of Smallpox, Orthopoxviruses Pathogenic for Humans 5(8) 817-826
  2. Foster, S., Parker, S., Lanier, R. The Role of Brincidofovir in Preparation for a Potential Smallpox Outbreak, 2017 October. Viruses.