"You have smallpox," are three words that you never want to hear, regardless of whether the "you" is you or any other human being. As I wrote previously for Forbes, the last natural case of smallpox occurred in 1977 and the World Health Organization (WHO) declared smallpox eradicated in 1980. That means that smallpox is not supposed to exist, with the exception of heavily guarded samples. Unfortunately, thanks to the wonderful existence of bioterrorism, where people try to deliberately give their fellow human beings a deadly disease, we can never say that smallpox will never re-appear.
That's why Friday's announcement that the U.S. Food and Drug Administration (FDA) has approved TPOXX as the first treatment for smallpox is significant. Hopefully, no one will need to take TPOXX anytime soon. And, no, you probably won't be seeing any TPOXX and smallpox advertisements with dancing happy people on television in the near future. However, TPOXX does help address an important need. Most people do not routinely get the smallpox vaccine anymore, unless they are regularly handling smallpox or in the military. Therefore, much of the world's population remains unprotected against this contagious disease that killed up to 30% of those infected and for thousands of years was a scourge of humankind. Without treatments for smallpox, exposing people to the virus could be like throwing sharp hardware supplies at them while they are in the shower. They could be screwed.
Therefore, options have been needed in case smallpox makes a return, either through a bio-terrorist attack, a lab accident, an unexpected mutation, Klingons visiting Earth, or some other unexpected event that brings the Variola major virus back into play. TPOXX, otherwise known as tecovirimat and developed by SIGA Technologies, now offers an option if someone does get infected. When a Variola major virus enters a human cell, it tries to hijack the cell's machinery to reproduce, making many copies of itself. The virus then induces a process in which these new copies are subsequently released from the infected cell to then go on and infect other cells. Tecovirimat is a small molecule drug that inhibits the function of p37, a protein needed to help the new smallpox viruses to be released from an infected cell. Inhibiting this protein can then halt a key process involved in spreading the virus.
SIGA submitted a New Drug Application (NDA) for TPOXX to the FDA in December of 2017 after human studies found no severe side effects and studies in non-human primates and rabbits demonstrated its efficacy in treating infections similar to human smallpox as reported in the New England Journal of Medicine and the journal Antimicrobial Agents and Chemotherapy. Of course, most humans are not exactly the same as monkeys and rabbits so it is not completely clear how efficacious the drug may be in humans.
The arrival of TPOXX also demonstrates the need for resources and incentives for researchers and companies to continue developing medications that meet such unmet needs. TPOXX is not like some blockbuster drugs for which you can expand its market by convincing more people to take it more often. You can't run commercials saying, "are you sure you don't have smallpox? Ask your doctor if you have smallpox." The demand for TPOXX will be in maintaining the stockpiles that are needed just in case a smallpox emergency arises. The efforts and funding from the U.S. Department of Health and Human Services’ Biomedical Advanced Research and Development Authority (BARDA) helped make TPOXX a reality.
All of this highlights the fact that the importance and potential of a drug are not always reflected in its immediate demand or the size of its market or what it may do to short-term profits and stock prices. Heck, even Viagra arose, so to speak, by accident based on the observed side effects of a cardiovascular medication.
