Tecovirimat, sold under the brand name Tpoxx among others, is an

antiviral medication Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Unlike most antibiotics, antiviral drugs do ...

with activity against

orthopoxviruses ''Orthopoxvirus'' is a genus of viruses in the family ''Poxviridae'' and subfamily ''Chordopoxvirinae''. Vertebrates, including mammals and humans, and arthropods serve as natural hosts. There are 12 species in this genus. Diseases associated wi ...

such as

smallpox Smallpox was an infectious disease caused by variola virus (often called smallpox virus) which belongs to the genus Orthopoxvirus. The last naturally occurring case was diagnosed in October 1977, and the World Health Organization (WHO) c ...

and

monkeypox Monkeypox (also called mpox by the WHO) is an infectious viral disease that can occur in humans and some other animals. Symptoms include fever, swollen lymph nodes, and a rash that forms blisters and then crusts over. The time from exposure to ...

. It is the first antipoxviral drug approved in the United States. It is an inhibitor of the orthopoxvirus VP37 envelope wrapping protein. The drug works by blocking cellular transmission of the virus, thus preventing the disease. Tecovirimat has been effective in laboratory testing; it has been shown to protect animals from

and rabbitpox and causes no serious side effects in humans. Tecovirimat was first used for treatment in December 2018, after a laboratory-acquired

vaccinia ''Vaccinia virus'' (VACV or VV) is a large, complex, enveloped virus belonging to the poxvirus family. It has a linear, double-stranded DNA genome approximately 190 kbp in length, which encodes approximately 250 genes. The dimensions of the ...

virus infection. Two million doses of tecovirimat are stockpiled in the US

Strategic National Stockpile The Strategic National Stockpile (SNS), originally called the National Pharmaceutical Stockpile (NPS), is the United States' national repository of antibiotics, vaccines, chemical antidotes, antitoxins, and other critical medical supplies. Its w ...

should an orthopoxvirus-based bioterror attack occur. The U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

(FDA) considers it to be a

first-in-class medication A first-in-class medication is a pharmaceutical that uses a "new and unique mechanism of action" to treat a particular medical condition. While the Food and Drug Administration's Center for Drug Evaluation and Research tracks first-in-class medicat ...

Medical uses

In the United States, tecovirimat is

indicated In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosis ...

for the treatment of human smallpox disease. In the European Union it is indicated for the treatment of smallpox, monkeypox, and cowpox.

Mechanism of action

Tecovirimat inhibits the function of a major

envelope protein A viral envelope is the outermost layer of many types of viruses. It protects the genetic material in their life cycle when traveling between host cells. Not all viruses have envelopes. Numerous human pathogenic viruses in circulation are encase ...

required for the production of extracellular virus. The drug prevents the virus from leaving an infected cell, hindering the spread of the virus within the body.

Chemistry

The first synthesis of tecovirimat was published in a patent filed by scientists at

Siga Technologies SIGA Technologies, Inc. is an American pharmaceutical company founded in 1995, currently based in New York City, which develops and sells pharmaceutical solutions for the antiviral treatment of smallpox, monkeypox, cowpox, and vaccinia complicatio ...

in 2004. It is made in two steps from

cycloheptatriene Cycloheptatriene (CHT) is an organic compound with the formula C7H8. It is a closed ring of seven carbon atoms joined by three double bonds (as the name implies) and four single bonds. This colourless liquid has been of recurring theoretical inter ...

. :

Diels–Alder reaction In organic chemistry, the Diels–Alder reaction is a chemical reaction between a conjugated diene and a substituted alkene, commonly termed the dienophile, to form a substituted cyclohexene derivative. It is the prototypical example of a peric ...

with

maleic anhydride Maleic anhydride is an organic compound with the formula C2H2(CO)2O. It is the acid anhydride of maleic acid. It is a colorless or white solid with an acrid odor. It is produced industrially on a large scale for applications in coatings and poly ...

forms the main ring system and a subsequent reaction with 4-trifluormethylbenzhydrazide gives the cyclic

imide In organic chemistry, an imide is a functional group consisting of two acyl groups bound to nitrogen. The compounds are structurally related to acid anhydrides, although imides are more resistant to hydrolysis. In terms of commercial applications, ...

of the drug.

History

Originally researched by the

National Institute of Allergy and Infectious Diseases The National Institute of Allergy and Infectious Diseases (NIAID, ) is one of the 27 institutes and centers that make up the National Institutes of Health (NIH), an agency of the United States Department of Health and Human Services (HHS). NIAID's ...

, the drug was owned by

Viropharma ViroPharma Incorporated was a pharmaceutical company that developed and sold drugs that addressed serious diseases treated by physician specialists and in hospital settings. The company focused on product development activities on viruses and hu ...

and discovered in collaboration with scientists at the

United States Army Medical Research Institute of Infectious Diseases The United States Army Medical Research Institute of Infectious Diseases (USAMRIID; pronounced: you-SAM-rid) is the U.S Army's main institution and facility for defensive research into countermeasures against biological warfare. It is located ...

. It is owned and manufactured by Siga Technologies. Siga and Viropharma were issued a patent for tecovirimat in 2012.

Clinical trials

As of 2009, the results of clinical trials support its use against smallpox and other related orthopoxviruses. It shows potential for a variety of uses including

preventive healthcare Preventive healthcare, or prophylaxis, consists of measures taken for the purposes of disease prevention.Hugh R. Leavell and E. Gurney Clark as "the science and art of preventing disease, prolonging life, and promoting physical and mental hea ...

, as a post-exposure therapeutic, as a therapeutic, and an adjunct to vaccination. Tecovirimat can be taken

by mouth Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are i ...

and as of 2008, was permitted for

phase II trial The phases of clinical research are the stages in which scientists conduct experiments with a health intervention to obtain sufficient evidence for a process considered effective as a medical treatment. For drug development, the clinical phases ...

s by the U.S.

(FDA). In

phase I trial The phases of clinical research are the stages in which scientists conduct experiments with a health intervention to obtain sufficient evidence for a process considered effective as a medical treatment. For drug development, the clinical phases ...

s, tecovirimat was generally well tolerated with no serious adverse events. Due to its importance for

biodefense Biodefense refers to measures to restore biosecurity to a group of organisms who are, or may be, subject to biological threats or infectious diseases. Biodefense is frequently discussed in the context of biowar or bioterrorism, and is generall ...

, the FDA designated tecovirimat for fast-track status, creating a path for expedited FDA review and eventual regulatory approval. On 13 July 2018, the FDA announced approval of tecovirimat for the treatment of smallpox. On 25 August 2022, the

AIDS Clinical Trials Group The AIDS Clinical Trials Group network (ACTG) is one of the largest HIV clinical trials organizations in the world, playing a major role in setting standards of care for HIV infection and opportunistic diseases related to HIV and AIDS in the Un ...

(ACTG) began a randomized, placebo-controlled, double-blinded trial on the safety and efficacy of tecovirimat for monkeypox, known as STOMP (Study of Tecovirimat for Human Monkeypox Virus), aiming to enroll at least 500 participants with acute monkeypox infection.

Society and culture

Legal status

In November 2021, the

Committee for Medicinal Products for Human Use The Committee for Medicinal Products for Human Use (CHMP), formerly known as Committee for Proprietary Medicinal Products (CPMP), is the European Medicines Agency's committee responsible for elaborating the agency's opinions on all issues regarding ...

of the

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Euro ...

adopted a positive opinion, recommending the granting of a marketing authorization under exceptional circumstances for the medicinal product tecovirimat siga, intended for the treatment of orthopoxvirus disease (smallpox, monkeypox,

cowpox Cowpox is an infectious disease caused by the ''cowpox virus'' (CPXV). It presents with large blisters in the skin, a fever and swollen glands, historically typically following contact with an infected cow, though in the last several decades more ...

, and

complications) in adults and in children who weigh at least The applicant for this medicinal product is Siga Technologies Netherlands B.V. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. Tecovirimat was approved for medical use in the

European Union The European Union (EU) is a supranational political and economic union of member states that are located primarily in Europe. The union has a total area of and an estimated total population of about 447million. The EU has often been des ...

in January 2022. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. In December 2021,

Health Canada Health Canada (HC; french: Santé Canada, SC)Health Canada is the applied title under the Federal Identity Program; the legal title is Department of Health (). is the Structure of the Canadian federal government#Departments, with subsidiary unit ...

approved oral tecovirimat for the treatment of smallpox in people weighing at least . As of August 2022, Tpoxx is available in the US only through the Strategic National Stockpile as a

Centers for Disease Control and Prevention The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georgi ...

investigational new drug. Intravenous Tpoxx has no lower weight cap and can be used in

infant An infant or baby is the very young offspring of human beings. ''Infant'' (from the Latin word ''infans'', meaning 'unable to speak' or 'speechless') is a formal or specialised synonym for the common term ''baby''. The terms may also be used to ...

s under the investigational new drug protocol.

References

External links

* * {{Portal bar , Medicine Antiviral drugs Benzamides Cyclopropanes Hydrazides Imides Nitrogen heterocycles Poxviruses Trifluoromethyl compounds Orphan drugs