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The Clinical Development of Ledipasvir/Sofosbuvir (LDV/SOF, Harvoni®)

  • Anu OsinusiEmail author
  • John G. McHutchison
Chapter
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Part of the Topics in Medicinal Chemistry book series (TMC, volume 32)

Abstract

The fixed-dose combination tablet of ledipasvir (LDV), an HCV NS5A inhibitor, and sofosbuvir (SOF), an HCV nucleotide analog NS5B polymerase inhibitor, was the first all-oral (one-pill once daily), interferon-free and ribavirin-free regimen approved for the treatment of patients with chronic hepatitis C. With over 5,900 HCV-infected patients enrolled in LDV/SOF clinical trials through late 2017, the accelerated clinical development program was able to generate safety and efficacy data across a broad range of patient populations. The initial registration trials demonstrated that 12 weeks of treatment with LDV/SOF resulted in high cure rates of over 95% in HCV genotype 1 patients regardless of historical negative treatment predictors including cirrhosis or prior treatment history. The program subsequently expanded to include other HCV genotypes and special populations with significant unmet medical need including but not limited to decompensated liver disease, HIV/HCV coinfection, posttransplantation, and children. With favorable pharmacokinetic properties, good safety profile, and high efficacy rates, the approval of LDV/SOF (Harvoni®) ushered in a new era of treatment and management for the millions of HCV-infected patients globally.

Keywords

Direct-acting antivirals HCV genotype 1 infection Hepatitis C virus NS5A inhibitors NS5B nucleotide inhibitors 

Abbreviations

DAAs

Direct-acting antivirals

FDC

Fixed-dose combination

HCV

Hepatitis C virus

HIV-1

Human immunodeficiency virus type 1

IFN

Interferon

LDV

Ledipasvir

Peg-IFN

Pegylated interferon

RBV

Ribavirin

SOF

Sofosbuvir

SVR

Sustained virologic response

Notes

Acknowledgements

The authors would like to thank the patients and their families as well as study site staff who participated in the clinical trials of Sovaldi and Harvoni.

Compliance with Ethical Standards

Conflict of Interest Anu Osinusi and John G. McHutchison are employees of Gilead Sciences, Inc.

Ethical Approval

All procedures performed in the 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 International Publishing AG, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Clinical Research, Liver Disease Therapeutic AreaGilead Sciences, Inc.Foster CityUSA
  2. 2.Clinical ResearchGilead Sciences, Inc.Foster CityUSA

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