SIGA Technologies, Inc. TPOXX® (tecovirimat, ST-246®), a novel small-molecule drug, is approved in the U.S., Canada, U.K., and Europe to treat smallpox. In addition, the European Medicines Agency (EMA) and the Norwegian Medicines Agency approvals include the treatment of monkeypox, cowpox, and complications from immunization with vaccinia.
TPOXX inhibits the viral maturation of the variola virus and other poxviruses by preventing the formation of a secondary viral envelope. In the absence of this envelope, viral particles remain inside the cell and cannot spread to and infect other cells. The World Health Organization (WHO) confirmed on May 30, 2022, that TPOXX is effective against a monkeypox virus (MPX) infection.
TPOXX was approved initially as oral capsules by the U.S. FDA in 2018. Then on May 19, 2022, the FDA approved the intravenous (IV) formulation of TPOXX. Following U.S. approval, Health Canada authorized oral TPOXX® for the treatment of human smallpox disease in adults and pediatric patients weighing at least 13 kg in November 2021. In addition, oral TPOXX® is supplied to both the Canadian Department of National Defence and the Public Health Agency of Canada for stockpiling as an essential countermeasure. And in January 2022, the European Medicines Agency issued its approval.
In September 2018, SIGA signed a contract with the Biomedical Advanced Research and Development Authority (BARDA) for additional procurement and development related to both oral and intravenous formulations of TPOXX. In addition, SIGA has collaborated with the DoD's Joint Program Executive Office for Chemical, Biological, Radiological, and Nuclear Defense (JPEO-CBRND) to develop the Post Exposure Prophylaxis (PEP) indication for TPOXX. This DoD work is supported by a separate development contract (Sept. 2020) of approximately $26 million. As a result, the DoD has drafted an Expanded Access Protocol (EAP) for TPOXX, which can be used for PEP purposes for certain DoD-affiliated personnel until the FDA approves TPOXX for PEP.
On May 23, 2022, the U.S. FDA published: Smallpox Preparedness and Response Updates. NDC Code(s): 50072-200-42.
SIGA has established a network with over 20 partners across discovery, pre-clinical, clinical, manufacturing, and supply chain that supported the development of TPOXX and the successful delivery of approximately $200 million of courses to the U.S. Strategic National Stockpile (SNS). SIGA Technologies, Inc. (NASDAQ: SIGA) is a New York-based (31 East 62nd Street, 10065) commercial-stage pharmaceutical company focused on the health security market.
Formula: C19H15F3N2O3; ChemSpider ID: 17281586; ChEMBL Id: 1257073; PubChem CID: 16124688; Monoisotopic mass376.103485 Da
The capsules include the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, hydroxypropyl methylcellulose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and sodium lauryl sulfate. The capsule shell comprises gelatin, FD&C blue #1, FD&C red #3, FD&C yellow #6, and titanium dioxide.
Oral TPOXX® (tecovirimat) is an orthopoxvirus VP37 envelope wrapping protein inhibitor. TPOXX was the first drug approved by the U.S. Food and Drug Administration expressly indicated to treat smallpox disease in adults and pediatric patients weighing at least 13 kg. Tecovirimat inhibits the production of extracellular viral forms, which are responsible for the systemic spread of infection, inhibiting virus-induced cytopathic effects. Tecovirimat does not inhibit the formation of intracellular forms of the virus; however, by inhibiting envelopment and therefore preventing the exit of viral particles from an infected cell, the smallpox infection is slowed to a point where the immune system can eliminate the virus.
Tecovirimat is a weak inducer of cytochrome P450 (CYP)3A and a weak inhibitor of CYP2C8 and CYP2C19. However, the effects are not expected to be clinically relevant for most substrates of those enzymes based on the magnitude of interactions and the duration of treatment of TPOXX.
The safety of TPOXX was evaluated in 359 healthy adult subjects ages 18-79 years in a Phase 3 clinical trial. Of the subjects who received at least one 600 mg dose of TPOXX, 59% were female, 69% were White, 28% were Black/African American, 1% were Asian, and 12% were Hispanic or Latino. Ten percent of the subjects who participated in the study were aged 65 or older. Of these 359 subjects, 336 subjects received at least 23 of 28 doses of 600 mg TPOXX in a twice-daily regimen for 14 days. The most frequently reported adverse reactions were headaches and nausea. Adverse reactions occurred in at least 2% of the TPOXX treatment group subjects. Co-administration of repaglinide and tecovirimat may cause mild to moderate hypoglycemia. Monitor blood glucose and monitor for hypoglycemic symptoms when administering TPOXX with repaglinide.
On May 27, 2022, the Motley Fool wrote 'SIGA Technologies: Solid Business With Means To Address Monkeypox Outbreak.'
As of March 31, 2022, the company's contract with BARDA contemplates up to approximately $602.5 million of payments, of which approximately $51.7 million of payments are included within the base period of performance of five years, approximately $239.7 million of payments are related to exercised options and up to approximately $311.1 million of payments are currently specified as unexercised options.
May 24, 2022 - The Lancet Infectious Disease published: Clinical features and management of human monkeypox: a retrospective (2018-2021) observational study in the UK. The patient was given 200 mg of oral tecovirimat twice daily for two weeks, had no adverse effects, and shed viral DNA for only ten days. 'We report the first use of antiviral agents in patients with monkeypox, with one receiving tecovirimat. The patient treated with tecovirimat had a shorter duration of symptoms and upper respiratory tract viral shedding than the other patients in the series, with no adverse events identified before discharge. However, several patients experienced prolonged viremia and upper respiratory tract viral shedding after crusting of all cutaneous lesions, leading to extended isolation in the hospital.
May 19, 2022 - SIGA Technologies, Inc. announced that the U.S. FDA approved the intravenous (IV) formulation of TPOXX for the treatment of smallpox. The IV formulation is an essential option for those unable to swallow the oral capsules of TPOXX.
May 12, 2022 - SIGA Technologies, Inc. announced that the U.S. DoD awarded a contract to SIGA to procure up to approximately $7.5 million of oral TPOXX. Roughly $3.6 million of oral TPOXX is targeted for delivery in 2022. The remainder is subject to an option at the sole discretion of the DoD.
May 5, 2022 - SIGA Technologies CEO Phil Gomez stated: "With the delivery in the first quarter of $7 million of IV TPOXX to the U.S. government, SIGA has expanded its TPOXX revenue base in the U.S. On the international front, the revenue base is also expanding with a new contract with jurisdiction in the Asia Pacific region. Under the new contract, approximately $3 million of oral TPOXX has been ordered for delivery in 2022."
May 2, 2022 - SIGA announced that it had initiated a clinical program to support a U.S. FDA label expansion for Post-Exposure Prophylaxis for oral TPOXX.
April 8, 2022 - The U.S. CDC's MMWr reported 'The patient completed a 32-day hospitalization that included treatment with tecovirimat because of severe disease. Hospital discharge had been delayed until a remaining lesion tested negative for Monkeypox virus DNA.'
January 10, 2022 - SIGA Technologies, Inc. announced that the European Medicines Agency (EMA) approved SIGA's Marketing Authorisation Application (MAA) for oral tecovirimat. The U.S. FDA approved the same formulation in July 2018 under the brand name TPOXX®. The EMA approval includes labeling for oral tecovirimat, indicating its use to treat smallpox, monkeypox, cowpox, and vaccinia complications following vaccination against smallpox. The MAA enables sales in European Union member states and Norway, Iceland, and Liechtenstein.
July 29, 2021 - SIGA Technologies, Inc. announced that it has entered into a collaboration with Oxford University in the U.K. to provide TPOXX® (tecovirimat) under an expanded access protocol to treat individuals affected by monkeypox in the Central African Republic.
July 13, 2018 - The U.S. Food and Drug Administration approved TPOXX (tecovirimat), the first drug with an indication for the treatment of smallpox. The FDA granted this application Fast Track and Priority Review designations. TPOXX also received Orphan Drug designation.
The first study compares the enrolled participants' immune response to the Jynneos smallpox vaccines to the immune response to Jynneos while on TPOXX treatment. The study is designed to determine if TPOXX interferes with developing an effective immune response to the vaccine. A second clinical study, also expected to commence in 2022, will look at developing an expanded safety dataset to support 28-day dosing of TPOXX for the post-exposure prophylaxis indication compared with the currently approved 14 days for treatment of smallpox indication.
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