AT-527

Bemnifosbuvir

Bemnifosbuvir

Chemical compound

Bemnifosbuvir (AT-527, RO7496998) is an antiviral drug invented by Atea Pharmaceuticals and licensed to Roche for clinical development, a novel nucleotide analog prodrug originally developed for the treatment of hepatitis C.[1][2] Bemnifosbuvir is the orally bioavailable hemisulfate salt of AT-511, which is metabolized in several steps to the active nucleotide triphosphate AT-9010, acting as an RNA polymerase inhibitor and thereby interfering with viral replication. Bemnifosbuvir has been researched for the treatment of coronavirus diseases such as that produced by SARS-CoV-2.[3] It showed good results in early clinical trials but had inconsistent results at later stages.[4][5] Bemnifosbuvir's Phase III study ended early as it failed to meet its primary endpoint of symptom alleviation and did not decrease viral load. However, the drug was well-tolerated and reduced relative hospitalization risk by 71%.[6]

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See also

References

  1. [1]
    Berliba E, Bogus M, Vanhoutte F, Berghmans PJ, Good SS, Moussa A, et al. (September 2019). "Safety, pharmacokinetics and antiviral activity of AT-527, a novel purine nucleotide prodrug, in HCV-infected subjects with and without cirrhosis". Antimicrobial Agents and Chemotherapy. 63 (12). doi:10.1128/AAC.01201-19. PMC 6879261. PMID 31570394.
  2. [2]
    Good SS, Moussa A, Zhou XJ, Pietropaolo K, Sommadossi JP (2020). "Preclinical evaluation of AT-527, a novel guanosine nucleotide prodrug with potent, pan-genotypic activity against hepatitis C virus". PLOS ONE. 15 (1): e0227104. Bibcode:2020PLoSO..1527104G. doi:10.1371/journal.pone.0227104. PMC 6949113. PMID 31914458.
  3. [3]
    Good SS, Westover J, Jung KH, Zhou XJ, Moussa A, La Colla P, et al. (March 2021). "AT-527, a Double Prodrug of a Guanosine Nucleotide Analog, Is a Potent Inhibitor of SARS-CoV-2 In Vitro and a Promising Oral Antiviral for Treatment of COVID-19". Antimicrobial Agents and Chemotherapy. 65 (4). doi:10.1128/AAC.02479-20. PMC 8097421. PMID 33558299.
  4. [4]
    Lowe D (19 October 2021). "AT-527 Fails a Phase II". In the Pipeline. Science.org.
  5. [5]
    Fidler B, Gardner J (19 October 2021). "Atea, Roche change plans for oral COVID-19 drug after trial setback". Biopharmadive.com.
  6. [6]
    Horga A, Saenz R, Yilmaz G, Simón-Campos A, Pietropaolo K, Stubbings WJ, Collinson N, Ishak L, Zrinscak B, Belanger B, Granier C, Lin K, C Hurt A, Zhou XJ, Wildum S, Hammond J (November 2023). "Oral bemnifosbuvir (AT-527) vs placebo in patients with mild-to-moderate COVID-19 in an outpatient setting (MORNINGSKY)". Future Virology. 18 (13). doi:10.2217/fvl-2023-0115. PMC 10621114. PMID 37928891.


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