3 August 2022

Sherwat A, Brooks JT, Birnkrant D, Kim P. Tecovirimat and the Treatment of Monkeypox – Past, Present, and Future Considerations. N Engl J Med. 2022 Aug 3. PubMed: https://pubmed.gov/35921403. Full text: https://doi.org/10.1056/NEJMp2210125

Monkeypox can cause serious illness, including ocular involvement, soft-tissue superinfections, and excruciating anogenital lesions. How to manage compassionate access to the antiviral drug tecovirimat whose safety and efficacy in humans have not been established? The article explains the basis for the drugs’s approval by the U.S. Food and Drug Administration (FDA) for the treatment of smallpox and the knowledge gaps that remain.

 

2 August 2022

Rojek A, Dunning J, Olliaro P. Monkeypox: how will we know if the treatments work? Lancet Infect Dis. 2022 Aug 2:S1473-3099(22)00514-X. PubMed: https://pubmed.gov/35931096. Full text: https://doi.org/10.1016/S1473-3099(22)00514-X

“Our primary motivations for treating monkeypox vary depending on severity and risk of transmission and, therefore, might shift focus between symptom relief, preventing complications, shortening the duration of patient isolation, or preventing spread of disease.

29 July 2022

Siegrist EA, Sassine J. Antivirals with Activity Against Monkeypox: A Clinically Oriented Review. Clin Infect Dis. 2022 Jul 29:ciac622. PubMed: https://pubmed.gov/35904001. Full text: https://doi.org/10.1093/cid/ciac622

The authors review basic pharmacology, animal models and experience in human patients of three antiviral agents with activity against monkeypox: cidofovir, brincidofovir, and tecovirimat. “Cidofovir, and its prodrug brincidofovir, are inhibitors of DNA replication with a broad spectrum of activity against multiple families of double-stranded DNA viruses. Tecovirimat has more specific activity against orthopoxviruses, and inhibits the formation of the extracellular enveloped virus necessary for cell-to-cell transmission.”  87 references.

 

29 June 2022

Harris E. Global Monkeypox Outbreaks Spur Drug Research for the Neglected Disease. JAMA. 2022 Jun 29. PubMed: https://pubmed.gov/35767293. Full text: https://doi.org/10.1001/jama.2022.11224

Monkeypox virus disease usually improves without specific treatment within a month, but the infection requires isolation to prevent transmission. In Africa, depending on the viral clade, it has been found to be fatal in 1% to 11%.

 

28 June 2022

Rizk JG, Lippi G, Henry BM, Forthal DN, Rizk Y. Prevention and Treatment of Monkeypox. Drugs. 2022 Jun 28:1-7. PubMed: https://pubmed.gov/35763248. Full text: https://doi.org/10.1007/s40265-022-01742-y

Key points: 1) Prevention and management of monkeypox is similar to that of other orthopoxvirus infections. 2) Immunization with smallpox vaccines (JYNNEOSTM and ACAM2000®) may have a protective effect against monkeypox virus and improve clinical manifestations. 3) Most patients have mild disease and recover without medical intervention, but treatment with antivirals or vaccinia immune globulin may be used in seriously ill or immunocompromised individuals.

 

24 May 2022

Adler H, Gould S, Hine P, et al. Clinical features and management of human monkeypox: a retrospective observational study in the UK. Lancet Infect Dis. 2022 May 24:S1473-3099(22)00228-6. PubMed: https://pubmed.gov/35623380. Full text: https://doi.org/10.1016/S1473-3099(22)00228-6

The authors report the first use of antiviral agents in patients with monkeypox, with three patients receiving brincidofovir  and one receiving tecovirimat.  While brincidofovir didn’t seem to confer any convincing clinical benefit, one 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.

 

15 September 2020

Russo AT, Grosenbach DW, Chinsangaram J, et al. An overview of tecovirimat for smallpox treatment and expanded anti-orthopoxvirus applications. Expert Rev Anti Infect Ther. 2021 Mar;19(3):331-344. PubMed: https://pubmed.gov/32882158. Full text: https://doi.org/10.1080/14787210.2020.1819791

The authors discuss the discovery and development of tecovirimat (TPOXX®; ST-246). The safety of TPOXX was evaluated in 359 healthy human volunteers without a smallpox infection. The most frequently reported side effects were headache, nausea and abdominal pain.

 

13 July 2018

FDA 20180713. FDA approves the first drug with an indication for treatment of smallpox. https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-indication-treatment-smallpox

The U.S. Food and Drug Administration approves TPOXX (tecovirimat), the first drug with an indication for treatment of smallpox. The safety of TPOXX was evaluated in 359 healthy human volunteers without a smallpox infection. The most frequently reported side effects were headache, nausea and abdominal pain.

 

5 July 2018

Grosenbach DW, Honeychurch K, Rose EA, et al. Oral Tecovirimat for the Treatment of Smallpox. N Engl J Med. 2018 Jul 5;379(1):44-53. PubMed: https://pubmed.gov/29972742. Full text: https://doi.org/10.1056/NEJMoa1705688

The authors investigated the efficacy of tecovirimat in nonhuman primate (monkeypox) and rabbit (rabbitpox) models. As a result, a dose of 600 mg twice daily for 14 days was selected for testing in humans.

 

12 December 2017

Reynolds MG, McCollum AM, Nguete B, Shongo Lushima R, Petersen BW. Improving the Care and Treatment of Monkeypox Patients in Low-Resource Settings: Applying Evidence from Contemporary Biomedical and Smallpox Biodefense Research. Viruses. 2017 Dec 12;9(12):380. PubMed: https://pubmed.gov/29231870. Full text: https://doi.org/10.3390/v9120380

Clinical support to mitigate the consequences of compromised skin and mucosa should include prevention and treatment of secondary bacterial infections (and other complications), ensuring adequate hydration and nutrition, and protecting vulnerable anatomical locations such as the eyes and genitals.

 

5 March 2011

Rice AD, Adams MM, Lampert B, et al. Efficacy of CMX001 as a prophylactic and presymptomatic antiviral agent in New Zealand white rabbits infected with rabbitpox virus, a model for orthopoxvirus infections of humans. Viruses. 2011 Feb;3(2):63-82. PubMed: https://pubmed.gov/21369346. Full text: https://doi.org/10.3390/v3020063

One of the first studies on brincidofovir (CMX001), a prodrug of cidofovir (CDV). Compared to CDV, brincidofovir has dramatically increased potency against all dsDNA viruses and, in contrast to CDV, is orally available and has shown no evidence of nephrotoxicity in healthy volunteers or severely ill transplant patients to date. The authors suggest that their results should also be applicable to monkeypox virus infections and for treatment of adverse reactions to smallpox vaccination.

 

17 February 2009

Jordan R, Goff A, Frimm A, et al. ST-246 antiviral efficacy in a nonhuman primate monkeypox model: determination of the minimal effective dose and human dose justification. Antimicrob Agents Chemother. 2009 May;53(5):1817-22. PubMed: https://pubmed.gov/19223621. Full text: https://doi.org/10.1128/AAC.01596-08

This study suggested that that administration of an oral dosage of Tecovirimat (ST-246) of 400 mg once daily for 14 days would  be effective for the prevention or treatment of smallpox or monkeypox infections in humans.

 

31 August 2004

De Clercq E, Neyts J. Therapeutic potential of nucleoside/nucleotide analogues against poxvirus infections. Rev Med Virol. 2004 Sep-Oct;14(5):289-300. PubMed: https://pubmed.gov/15334537. Full text: https://doi.org/10.1002/rmv.439

Early data on the activity of nucleoside and nucleotide analogues against poxvirus.