It's best to be prepared: FDA approves a drug that no one needs (and hopefully never will)

Yes, you read that right. On July 13, 2018, the FDA approved a drug for treating a disease that no one in the entire world is suffering from. That drug is TPOXX (tecovirimat) from Siga Technologies Inc. (Siga), and it was approved for treating smallpox. Maybe you remember reading about smallpox in history books. In 1980, the World Health Organization (WHO) declared that smallpox had been eradicated from the face of the Earth. So why would any company go to the trouble of developing and then applying for approval of a drug that has no patients that need it?

That can be explained in one word: bioterrorism! While the smallpox virus, called variola, is no longer circulating among the world's populations, there is a grave concern that there are laboratory samples of the virus still in the hands of some governments or private labs. So there is the potential (however small) for the creation of a smallpox bioweapon by a government or by a terrorist group who managed to steal samples of the virus. More about the TPOXX approval can be found in a press release on the  FDA's web site.

What is especially interesting about the TPOXX approval is how the drug was approved for use in humans without there being any patients suffering from the disease. Testing was solely performed on animals who were deliberately infected with their species' own specific "pox" disease, and then treated with TPOXX. As described in the FDA press release:
TPOXX was approved under the FDA’s Animal Rule, which allows efficacy findings from adequate and well-controlled animal studies to support an FDA approval when it is not feasible or ethical to conduct efficacy trials in humans.
 The drug label shows the results of those tests in cynomolgus macaques and in New Zealand white rabbits. In both cases TPOXX reduced deaths by a significant degree over untreated animals.

TPOXX was, in fact, administered to healthy human volunteers in order to determine its safety. The most common side effects were headache, nausea and abdominal pain. More details about the adverse events are found in the drug label.

Orange Book Listings

Since the active ingredient in TPOXX, tecovirimat, was never previously approved in the U.S., it received New Chemical Entity (NCE) exclusivity. That means that a generic company cannot apply for approval of a generic version of TPOXX for five years after approval, except that they can apply for approval after four years if they challenge at least one of the patents that Siga listed in the Orange Book for TPOXX.

In addition to the NCE exclusivity, the FDA's Electronic Orange Book shows six patents for TPOXX with expiration dates ranging from 2024 to 2031. Here are the TPOXX Orange Book listings in my Orange Book Companion® format in which the NDA number and patent numbers are links to the TPOXX record in the FDA's Electronic Orange Book and to the text of the patent at the USPTO, respectively:

TPOXX (CAPSULE) TECOVIRIMAT
NDA Applicant: SIGA TECHNOLOGIES      NDA No.: 208627  Prod. No.: 001 RX (200MG)
PatentsExpirationPatented Use
Pat. No. 7737168 Compounds, compositions, and methods for treatment and prevention of orthopoxvirus infections and associated diseases
Claim Types: Method of use
May 3, 2027U-2346: Treatment of human smallpox disease caused by variola virus in adults and pediatric patients weighing at least 13 kg
Pat. No. 8039504  DP* Chemicals, compositions, and methods for treatment and prevention of orthopoxvirus infections and associated diseases
Claim Types: Formulation
Jul 23, 2027
Pat. No. 8124643 DS* DP* Compounds, compositions and methods for treatment and prevention of orthopoxvirus infections and associated diseases
Claim Types: Composition; Compound
Jun 18, 2024
Pat. No. 8530509 DP* Compounds, compositions and methods for treatment and prevention of orthopoxvirus infections and associated diseases
Claim Types: Composition
Jun 18, 2024
Pat. No. 8802714 Compounds, compositions and methods for treatment and prevention of orthopoxvirus infections and associated diseases
Claim Types: Method of use
Jun 18, 2024U-2346: Treatment of human smallpox disease caused by variola virus in adults and pediatric patients weighing at least 13 kg
Pat. No. 9339466 DS* DP* Polymorphic forms of ST-246 and methods of preparation
Claim Types: New polymorph, salt or hydrate; Composition; Process
Mar 23, 2031
ExclusivityExpirationExclusivity Description
Exclusivity Code: NCE - New chemical entityJul 13, 2023

Based on the presence of patents that cover the approved compound, composition and the only approved use, the sole path to approval for a generic challenger prior to May 3, 2027 would be an invalidity decision. Although the '504 formulation patent contains an extremely broad claim 1, a creative generic challenger might still find a way around it. The '466 Form I polymorph patent would likely not protect TPOXX since many more polymorphs of tecovirimat are probably waiting to be discovered!

In the meantime, why would a generic drug company want to enter a market with a drug that has no patients that need it? Sure, there will be government contracts to be had so that stockpiles of tecovirimat capsules can be maintained as a precaution. However, would such contracts be lucrative enough to tempt a generic challenger to dive in? Only time will tell.

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