In April 2021 the FDA Approved a Drug to Treat Smallpox, which was eradicated in 1980 – what were they preparing for?

[6/4/2021] The U.S. Food and Drug Administration today approved Tembexa (brincidofovir) to treat smallpox. Although the World Health Organization declared smallpox, a contagious and sometimes fatal infectious disease, eradicated in 1980, there have been longstanding concerns that the virus that causes smallpox, the variola virus, could be used as a bioweapon.

Before its eradication in 1980, the variola virus mainly spread by direct contact among people. Symptoms typically began 10 to 14 days after infection and included fever, exhaustion, headache, and backache. A rash consisting of small, pink bumps progressed to pus-filled sores before it crusted over and scarred. Complications of smallpox included encephalitis (inflammation of the brain), corneal ulcerations (an open sore on the clear, front surface of the eye), and blindness.

Although naturally occurring smallpox no longer exists, concerns about potential uses of variola virus as a bioweapon has made smallpox drug development an important component of the U.S. medical countermeasures response.

Because smallpox is eradicated, the effectiveness of Tembexa 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. More animals treated with Tembexa survived compared to the animals treated with placebo. FDA approved Tembexa under the agency’s 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.

Safety information to support approval of Tembexa was derived from clinical trials of the drug for a non-smallpox indication, primarily from patients who received hematopoietic stem cell transplants.  An increased risk of death was seen in another disease (Cytomegalovirus disease – a viral infection) when Tembexa was used for a longer-than-recommended duration (longer than once a week for two weeks on days 1 and 8). Tembexa is only approved for the treatment of smallpox.

The most common side effects when using Tembexa are diarrhea, nausea, vomiting, and abdominal pain.

Tembexa received priority review, fast track and orphan drug designations. Priority review directs overall attention and resources to the evaluation of applications for drugs that, if approved, would be significant improvements in the safety or effectiveness of the treatment, diagnosis or prevention of serious conditions when compared to standard applications. Fast track is designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need. Orphan drug designation provides incentives to assist and encourage the development of drugs for rare diseases.

Tembexa was developed in conjunction with the U.S. Department of Health and Human Services’ Biomedical Advanced Research and Development Authority (BARDA). FDA granted approval of Tembexa to Chimerix Inc.

Related Information

• Smallpox Preparedness and Response Updates from FDA
• Smallpox (Variola Virus) Infection: Developing Drugs for Treatment or Prevention Guidance for Industry
• CDC: Smallpox