The drug works by blocking cellular transmission of orthopoxviruses, thus preventing disease.[9]
Tecovirimat has been effective in laboratory testing; it has been shown to protect animals frommpox andrabbitpox and causes no serious side effects in humans.[6] Tecovirimat was first used for treatment in December 2018, after a laboratory-acquiredvaccinia virus infection.[10]
In the United States, tecovirimat isindicated for the treatment of humansmallpox disease.[4][14]
In the European Union it is indicated for the treatment of smallpox,mpox, andcowpox.[5]Tecovirimat can be takenby mouth and should be taken with a fatty meal.[15] While tecovirimat did not show efficacy against mpox in monotherapy in clinical setting, in vitro assays showed strong inhibition of bothvaccinia andmpox incombination therapies.[16]
Tecovirimat inhibits the function of orthopoxvirus VP37 envelope wrapping protein,[4] a majorenvelope protein required for the production of extracellular virus. Tecovirimat acts as a molecular glue that promotes the dimerization of VP37.[17] The drug prevents the virus from leaving an infected cell, hindering the spread of the virus within the body.[18]
Antimicrobial resistance to tecovirimat was described in vitro in cowpox virus during treatment already in 2005, prior to licensure.[15] Since the global2022–2023 mpox outbreak, resistance has been described with long treatment courses among severely immunocompromised persons, but also in people without prior treatment, suggestinghuman-to-human transmission.[15] Tecovirimat resistance mutations identified in clinicalMPXV isolates map to the VP37 dimer interface and prevent drug-induced dimerization.[17]
The first synthesis of tecovirimat was published in a patent filed by scientists atSIGA Technologies in 2004. It is made in two steps fromcycloheptatriene.[19]
As of 2009, the results of clinical trials supported its use against smallpox and other related orthopoxviruses. It showed potential for a variety of uses includingpreventive healthcare, as a post-exposure therapeutic, as a therapeutic, and an adjunct to vaccination.[24]
As of 2008, it was permitted forphase II trials by the U.S.Food and Drug Administration (FDA). Inphase I trials, tecovirimat was generally well tolerated with no serious adverse events.[25] Due to its importance forbiodefense, the FDA designated tecovirimat for fast-track status, creating a path for expedited FDA review and eventual regulatory approval. In July 2018, the FDA approved tecovirimat for the treatment of smallpox.[26] the first antipoxviral drug approved in the United States.[27][28] In August 2022, theAIDS Clinical Trials Group (ACTG) began a randomized, placebo-controlled, double-blinded trial on the safety and efficacy of tecovirimat for mpox, known as STOMP (Study of Tecovirimat for Human mpox Virus), aiming to enroll at least 500 participants with acute mpox infection.[29][30]
In November 2021, theCommittee for Medicinal Products for Human Use of theEuropean Medicines Agency recommended to grant SIGA Technologies Netherlands B.V a marketing authorization under exceptional circumstances for tecovirimat, intended to treat orthopoxvirus disease (smallpox, mpox,cowpox, andvaccinia complications) in adults and in children who weigh at least 13 kilograms (29 lb)[31] Tecovirimat was approved for medical use in theEuropean Union in January 2022.[5][32][33]
In December 2021,Health Canada approved oral tecovirimat for the treatment of smallpox in people weighing at least 13 kilograms (29 lb).[1][34]
As of 2024, tecovirimat use in the US outside of a clinical trial should adhere to the CDCInvestigational New Drug protocol in order to prevent mutations and to include surveillance to prevent spread of resistant virus.[15]
^abc"Tecovirimat SIGA EPAR".European Medicines Agency. 10 November 2021.Archived from the original on 16 May 2022. Retrieved23 April 2022. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
^abAU patent 2004249250, Bailey, Thomas R.; Jordan, Robert & Rippin, Susan R., "Compounds, compositions and methods for treatment and prevention of orthopoxvirus infections and associated diseases", published 29 December 2004, assigned to SIGA Pharmaceuticals Inc
^Hughes DL (2019). "Review of the Patent Literature: Synthesis and Final Forms of Antiviral Drugs Tecovirimat and Baloxavir Marboxil".Organic Process Research & Development.23 (7):1298–1307.doi:10.1021/acs.oprd.9b00144.S2CID197172102.
^"Tecovirimat SIGA: Pending EC decision".European Medicines Agency. 11 November 2021.Archived from the original on 13 November 2021. Retrieved13 November 2021. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
