Tecovirimat 200mg capsules

BACKGROUND: Tecovirimat is an antiviral drug that was used compassionately for treating mpox in high-income settings during the 2022 global outbreak. Randomized controlled trials of its efficacy have not yet been completed. OBJECTIVES: To describe medication adherence, tolerability and clinical outcomes of adults receiving open-label tecovirimat for mpox infection. METHODS: We conducted a prospective observational study and a retrospective case series of adults with mpox cared for at three academic hospitals in Toronto, Canada, between May and August 2022. We present a descriptive analysis of those prescribed oral tecovirimat 600 mg twice daily for 14 days for the management of severe manifestations. RESULTS: Of 69 consenting participants, all were cisgender men, of whom 60 (87%) identified as gay, and 6 (9%) as bisexual. Nearly half (46%) were living with HIV, with a median (IQR) CD4 count of 468 (328-678) cells/mm3, among whom plasma HIV RNA was <20 copies/mL in 29 (91%) participants. One-third (33%) of participants received tecovirimat during the course of their illness. All participants experienced a decline in number of symptoms over time, but three treated participants initially experienced worsening symptoms despite therapy. Self-reported adherence to tecovirimat was excellent and tolerability was good. CONCLUSIONS: Our experience prescribing tecovirimat for mpox suggests it is safe and well tolerated, but the evolution of symptoms in some tecovirimat-treated patients underscores the ongoing uncertainty regarding its efficacy. In the context of considerable community demand for the drug, efforts should be made to connect mpox patients to rigorous randomized controlled trials, given this ongoing clinical equipoise.

Abstract licence: CC BY-NC

During the 2022 multinational outbreak of monkeypox virus (MPXV) infection, the antiviral drug tecovirimat (TPOXX; SIGA Technologies, Inc., https://www.siga.com) was deployed in the United States on a large scale for the first time. The MPXV F13L gene homologue encodes the target of tecovirimat, and single amino acid changes in F13 are known to cause resistance to tecovirimat. Genomic sequencing identified 11 mutations previously reported to cause resistance, along with 13 novel mutations. Resistant phenotype was determined using a viral cytopathic effect assay. We tested 124 isolates from 68 patients; 96 isolates from 46 patients were found to have a resistant phenotype. Most resistant isolates were associated with severely immunocompromised mpox patients on multiple courses of tecovirimat treatment, whereas most isolates identified by routine surveillance of patients not treated with tecovirimat remained sensitive. The frequency of resistant viruses remains relatively low (<1%) compared with the total number of patients treated with tecovirimat.

Abstract licence: CC BY

Tecovirimat (ST-246 or TPOXX) is an antiviral agent developed as part of a U.S. biodefense initiative aimed at addressing Orthopoxvirus infections, including smallpox and mpox. Although smallpox was declared eradicated in 1980, the potential for its reemergence as a biothreat persists due to illegal stockpiling and the possibility of laboratory synthesis. The F13 protein, which plays a critical role in the formation of extracellular viral particles, serves as the primary target for tecovirimat, inhibiting the transition from intracellular mature viruses (IMVs) to intracellular enveloped viruses (IEVs). Recent research indicates that tecovirimat stabilizes F13 homodimers as a molecular glue, effectively disrupting viral wrapping processes. However, the identification of tecovirimat-resistant mutations, particularly in immunocompromised individuals, highlights the urgent need for ongoing monitoring and the development of next-generation antiviral therapies. Investigating the structural dynamics of F13 and its interactions with tecovirimat may provide crucial insights into overcoming resistance mechanisms and improving therapeutic efficacy.

Abstract licence: CC BY

Abstract Introduction Tecovirimat (TPOXX) is an effective antiviral medication recommended for treating smallpox and other Orthopoxvirus infections. With the rise in monkeypox (mpox) cases globally, there is an urgent need to explore therapeutic options to manage potential outbreaks. Methodology A literature search was conducted using keywords from Scopus and ClinicalTrials.gov. English studies from 2018 to 2024 were included. Results Ten studies assessing the effectiveness and safety of tecovirimat for poxvirus infections were evaluated, reporting diverse findings across different patient populations and study designs. Clinical trials have shown significant therapeutic potential. Various doses of tecovirimat were used in rabbit and mpox models. Early intervention slowed disease progression in vulnerable populations, such as people living with HIV (PLWHIV). Recovery times, virus eradication, and symptom relief varied among studies, but wider access and usage showed better clinical symptoms and tolerable side effects. Tecovirimat’s efficacy against circulating strains has been experimentally demonstrated. Conclusion Tecovirimat shows promise for treating poxvirus infections. Clinical trials are expected to provide more evidence-based findings to inform future therapeutic approaches and public health campaigns. Future research should explore tecovirimat’s potential in managing emerging poxvirus outbreaks, such as borealpox and mpox, to strengthen and promote public health.

Abstract licence: CC BY

BACKGROUND: Tecovirimat is available for the treatment of mpox (formerly known as monkeypox) in Europe and the United States, on the basis of findings from efficacy studies in animals and safety evaluations in healthy humans. Evidence from randomized, controlled trials of safety and efficacy in patients with mpox is lacking. METHODS: We conducted a double-blind, randomized, placebo-controlled trial of tecovirimat in patients with mpox in the Democratic Republic of Congo (DRC). Patients with at least one mpox skin lesion and positive polymerase-chain-reaction results for clade I MPXV were assigned in a 1:1 ratio to receive tecovirimat or placebo. All patients received supportive care. The primary end point was resolution of mpox lesions, measured in number of days after randomization. Safety was also assessed. RESULTS: From October 7, 2022, through July 9, 2024, a total of 597 patients underwent randomization - 295 to receive tecovirimat and 302 to receive placebo. The median time from randomization to lesion resolution was 7 days with tecovirimat and 8 days with placebo; the competing-risks hazard ratio for lesion resolution was 1.13 (95% confidence interval [CI], 0.97 to 1.31; P = 0.14). Results were similar whether patients began the trial regimen within 7 days after the reported onset of symptoms (competing-risks hazard ratio, 1.16; 95% CI, 0.98 to 1.37) or more than 7 days after onset (competing-risks hazard ratio, 1.00; 95% CI, 0.71 to 1.40). Overall mortality was 1.7%, which was lower than the case fatality rate of 4.6% reported in the DRC in 2023. At 14 days, the percentages of patients who had blood, lesion, and oropharyngeal samples negative for MPXV by PCR were similar in the two groups. Adverse events occurred in 72.9% of the patients in the tecovirimat group and 70.5% of those in the placebo group, and serious adverse events were reported in 5.1% and 5.0%, respectively. CONCLUSIONS: Tecovirimat did not reduce the number of days to lesion resolution in patients with mpox caused by clade I MPXV. No safety concerns were identified. (Funded by the National Institute of Allergy and Infectious Diseases and others; PALM007 ClinicalTrials.gov number, NCT05559099.).

Abstract licence: CC BY-NC-ND

Mpox is a zoonotic disease endemic to Central and West Africa. Since 2022, two human-adapted monkeypox virus (MPXV) strains have caused large outbreaks outside these regions. Tecovirimat is the most widely used drug to treat mpox. It blocks viral egress by targeting the viral phospholipase F13; however, the structural details are unknown, and mutations in the F13 gene can result in resistance against tecovirimat, raising public health concerns. Here we report the structure of an F13 homodimer using X-ray crystallography, both alone (2.1 Å) and in complex with tecovirimat (2.6 Å). Combined with molecular dynamics simulations and dimerization assays, we show that tecovirimat acts as a molecular glue that promotes dimerization of the phospholipase. Tecovirimat resistance mutations identified in clinical MPXV isolates map to the F13 dimer interface and prevent drug-induced dimerization in solution and in cells. These findings explain how tecovirimat works, allow for better monitoring of resistant MPXV strains and pave the way for developing more potent and resilient therapeutics.

Abstract licence: CC BY