title: Development of sofosbuvir for the treatment of hepatitis C virus infection.
abstract: The nucleotide analog NS5B polymerase inhibitor sofosbuvir was approved by the U.S. Food and Drug Administration (FDA) in December 2013 for the treatment of chronic hepatitis C virus (HCV) infection in combination with ribavirin or peginterferon and ribavirin. Sofosbuvir was developed to meet an urgent medical need for shorter, safer, simplified, more effective HCV treatment regimens and to reduce or eliminate the need for peginterferon. New treatment regimens were especially required for patient populations with limited treatment options, including patients who had failed prior HCV therapy, those with compensated and decompensated cirrhosis, and those who were either intolerant of or had contraindications to interferon. Sofosbuvir plus ribavirin for patients with genotype 2 or 3 HCV infection was the first approved all-oral treatment option. Sofosbuvir is also the backbone of the first regimen available for patients awaiting liver transplantation to prevent HCV recurrence, as well as the first oral interferon-free regimen for patients coinfected with HCV and HIV. This paper describes the development of sofosbuvir up to its original FDA approval.
authors.affiliation: Texas Liver Institute, University of Texas Health Science Center, San Antonio, Texas.
authors.forename: Eric
authors.initials: E
authors.lastname: Lawitz
authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Ira M
authors.initials: IM
authors.lastname: Jacobson
authors.affiliation: University of Florida, Gainesville, Florida.
authors.forename: David R
authors.initials: DR
authors.lastname: Nelson
authors.affiliation: Medical Center, Johann Wolfgang Goethe University, Frankfurt am Main, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Sulkowski
authors.affiliation: Hospital Universitario Val d'Hebron, Barcelona, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Esteban
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: Diana
authors.initials: D
authors.lastname: Brainard
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: John
authors.initials: J
authors.lastname: McNally
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: William T
authors.initials: WT
authors.lastname: Symonds
authors.affiliation: Gilead Sciences, Foster City, California.
authors.forename: John G
authors.initials: JG
authors.lastname: McHutchison
authors.affiliation: Mount Sinai School of Medicine, New York, New York.
authors.forename: Douglas
authors.initials: D
authors.lastname: Dieterich
authors.affiliation: Auckland City Hospital, Auckland, New Zealand.
authors.forename: Edward
authors.initials: E
authors.lastname: Gane
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D055808:Drug Discovery; D016174:Hepacivirus / Q000187:drug effects; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D000069474:Sofosbuvir / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000998:Antiviral Agents; D000069474:Sofosbuvir
keywords: direct acting antivirals; drug development; hepatitis C; sofosbuvir