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

  • John O. LinkEmail author
Chapter
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Part of the Topics in Medicinal Chemistry book series (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.

Keywords

Direct-acting antiviral GS-5885 Harvoni® HCV LDV/SOF Ledipasvir NS5A inhibitor NS5B nucleotide inhibitor Single-tablet regimen 

Notes

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.

Compliance with Ethical Standards

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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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Medicinal Chemistry, Gilead SciencesFoster CityUSA

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