Life cycle of Tecovirimat authorized to treat human monkeypox infection in EU has been extended by reformulation with HPBCD by the originator Siga Technologies.

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Tecovirimat SIGA (marketed under the trade name TPOXX® in USA) is an oral medicine to treat smallpox, monkeypox and cowpox, three infections caused by viruses belonging to the same family (orthopoxviruses). It is also used to treat complications that can happen following vaccination against smallpox. Tecovirimat SIGA is used in adults and children weighing at least 13 kg. The active substance tecovirimat was formerly designated as ST-246. The European Medicines Agency considered that Tecovirimat SIGA is effective at reducing mortality caused by smallpox, monkeypox and cowpox, based on animal studies. While the safety of the medicine was assessed in non-infected people, the side effects of Tecovirimat SIGA are expected to be similar in infected people and are considered acceptable. The European Medicines Agency therefore decided that Tecovirimat SIGA’s benefits are greater than its risks and it can be authorised for use in the EU. There are no other treatments authorised for the monkeypox and cowpox infections, which although rare can be fatal. In addition, while smallpox has been eradicated, this is an extremely serious infection, for which no treatment exists should an outbreak occur. Tecovirimat SIGA has been authorised under ‘exceptional circumstances’. [1,2]

A recent paper in Lancet Infectious Diseases features the clinical data related to treatment of human monkeypox infection by tecovirimat [3].

The poor solubility of ST-246 in water (<0.1 mg/mL) and in pharmaceutically acceptable pH buffers creates an impediment to making safe and effective ST-246 liquid formulations. Siga Technologies filed a patent application in the USA on 2020-01-02 and was granted quite rapidly in the same year, in December 2020. [4] The granted patent has two claims:

1. A process for preparing a water-soluble solid ST-246 pharmaceutical formulation comprising:
a) mixing ST-246 with cyclodextrin in a pharmaceutically acceptable liquid carrier;
b) optionally filtering the mixture of step a); and
c) lyophilizing said mixture.

2. The process of claim 1, wherein said cyclodextrin is hydroxypropyl-β-cyclodextrin and/or sulfobutyl-ether-β-cyclodextrin.

The solubilizing potencies of three cyclodextrins suitable for parenteral application were compared:

Based on the solubility studies, HPBCD of the lower DS proved to be the best solubilizer of the drug out of the panel of test CD derivatives.

On May 19, 2022, SIGA Received approval from the FDA for Intravenous (IV) Formulation of TPOXX® (tecovirimat). FDA approval provides an important option for those unable to take oral formulation of TPOXX. [5] The product is a single-dose vial containing 200 mg of tecovirimat in 20 mL for further
dilution prior to intravenous infusion. 8 g dose of hydroxypropyl-β-cyclodextrin (per 200 mg tecovirimat/20 mL solution) is applied to solubilize the drug. The product contains only Hydroxypropyl Betadex, NF (hydroxypropyl β-cyclodextrin) and Water for Injection, USP/NF besides the active pharmaceutical ingredient. [6] In the moment the product is indicated for the treatment of human smallpox disease in adults and pediatric patients weighing at least 3 kg.







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