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The Discovery of Ledipasvir (GS-5885): The Potent Once-Daily Oral HCV NS5A Inhibitor in the Single-Tablet Regimen Harvoni®

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HCV: The Journey from Discovery to a Cure

Part of the book series: Topics in Medicinal Chemistry ((TMC,volume 32))

Abstract

The advent of direct-acting antiviral agents (DAAs) has revolutionized the treatment and cure of chronic hepatitis C virus (HCV) infection. Herein is described the discovery of ledipasvir (LDV), an orally available HCV nonstructural protein 5A inhibitor with picomolar antiviral potency and a long pharmacokinetic half-life. The combination of LDV with the nonstructural protein 5B inhibitor sofosbuvir (SOF) is Harvoni® and represents the first approved single-tablet regimen for the treatment of HCV infection. This safe simple and efficacious regimen affords clinical trial cure rates over 95% and comparable effectiveness in real-world studies and has treatment durations as short as 8 weeks. The approval of Harvoni® heralded a new era for the treatment of HCV infection.

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Notes

  1. 1.

    https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/204671s002lbl.pdf. Accessed 4 Dec 2018.

  2. 2.

    Volume I, HCV: The Journey from Discovery to a Cure.

  3. 3.

    https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/205834s001lbl.pdf. Accessed 10 June 2018.

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Acknowledgment

The author would like to thank the Gilead research and development colleagues that discovered and developed ledipasvir and the clinical collaborators and patients who made this work possible.

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Authors and Affiliations

  1. Medicinal Chemistry, Gilead Sciences, Foster City, CA, USA

    John O. Link

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  1. John O. Link
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Correspondence to John O. Link .

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Editors and Affiliations

  1. Arbutus Biopharma, Inc., Warminster, PA, USA

    Michael J. Sofia

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Conflict of Interest: John O. Link is an employee of Gilead Sciences, Inc.

Ethical Approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed Consent: Informed consent was obtained from all individual participants included in the study.

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Link, J.O. (2019). The Discovery of Ledipasvir (GS-5885): The Potent Once-Daily Oral HCV NS5A Inhibitor in the Single-Tablet Regimen Harvoni®. In: Sofia, M. (eds) HCV: The Journey from Discovery to a Cure. Topics in Medicinal Chemistry, vol 32. Springer, Cham. https://doi.org/10.1007/7355_2019_66

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