Efficacy of nucleotide polymerase inhibitor sofosbuvir plus the NS5A inhibitor ledipasvir or the NS5B non-nucleoside inhibitor GS-9669 against HCV genotype 1 infection

Edward J. Gane, Catherine A. Stedman, Robert H. Hyland, Xiao Ding, Evguenia Svarovskaia, G. Mani Subramanian, William T. Symonds, John G. McHutchison, Phillip S. Pang

Research output: Contribution to journalArticle

Abstract

Background & Aims We evaluated an all-oral regimen comprising the nucleotide polymerase inhibitor sofosbuvir (SOF) with the NS5A inhibitor ledipasvir (LDV) or the NS5B non-nucleoside inhibitor GS-9669 in patients with genotype 1 hepatitis C virus (HCV) infection. Methods A total of 113 patients were enrolled. Sofosbuvir (400 mg once daily) and LDV (90 mg once daily) plus ribavirin (RBV) were given for 12 weeks to treatment-naïve (TN) patients (n = 25) and those who did not respond to previous therapy (prior null responders, n = 9). Sofosbuvir and GS-9669 (500 mg once daily) plus RBV were given for 12 weeks to TN patients (n = 25) and prior null responders (n = 10). Additionally, prior null responders with cirrhosis were randomly assigned to groups given a fixed-dose combination of SOF and LDV, with RBV (n = 9) or without RBV (n = 10). Finally, a group of TN patients received SOF, LDV, and RBV for 6 weeks (n = 25). The primary efficacy end point was sustained virologic response 12 weeks after therapy (SVR12). Results SVR12 was achieved by 25 of 25 (100%) TN patients receiving SOF, LDV, and RBV and 23 of 25 (92%) of those receiving SOF, GS-9669, and RBV. Of TN patients receiving 6 weeks of SOF, LDV, and RBV, 17 of 25 (68%) achieved SVR12. All noncirrhotic prior null responders receiving 12 weeks of SOF along with another direct-acting antiviral agent plus RBV achieved SVR12 - 9 of 9 (100%) of those receiving SOF, LDV, and RBV and 10 of 10 (100%) of those receiving SOF, GS-9669, and RBV. Among cirrhotic prior null responders, SVR12 was achieved by 9 (100%) of those receiving SOF, LDV, and RBV and 7 (70%) of those receiving SOF and LDVD without RBV. The most common reported adverse events were headache, fatigue, and nausea. Conclusions The combination of SOF and a second direct-acting antiviral agent is highly effective in TN patients with HCV genotype 1 infection and in patients that did not respond to previous treatment. ClinicalTrials.gov ID NCT01260350.

Original languageEnglish (US)
JournalGastroenterology
Volume146
Issue number3
DOIs
StatePublished - Mar 2014
Externally publishedYes

Fingerprint

Ribavirin
Hepacivirus
Nucleotides
Genotype
Infection
Therapeutics
GS-9669
Sofosbuvir
ledipasvir
Antiviral Agents
Virus Diseases
Nausea
Fatigue
Headache
sofosbuvir drug combination ledipasvir
Fibrosis

Keywords

  • Clinical Trial
  • DAA
  • Drug
  • Liver Cirrhosis

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Efficacy of nucleotide polymerase inhibitor sofosbuvir plus the NS5A inhibitor ledipasvir or the NS5B non-nucleoside inhibitor GS-9669 against HCV genotype 1 infection. / Gane, Edward J.; Stedman, Catherine A.; Hyland, Robert H.; Ding, Xiao; Svarovskaia, Evguenia; Subramanian, G. Mani; Symonds, William T.; McHutchison, John G.; Pang, Phillip S.

In: Gastroenterology, Vol. 146, No. 3, 03.2014.

Research output: Contribution to journalArticle

Gane, Edward J. ; Stedman, Catherine A. ; Hyland, Robert H. ; Ding, Xiao ; Svarovskaia, Evguenia ; Subramanian, G. Mani ; Symonds, William T. ; McHutchison, John G. ; Pang, Phillip S. / Efficacy of nucleotide polymerase inhibitor sofosbuvir plus the NS5A inhibitor ledipasvir or the NS5B non-nucleoside inhibitor GS-9669 against HCV genotype 1 infection. In: Gastroenterology. 2014 ; Vol. 146, No. 3.
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abstract = "Background & Aims We evaluated an all-oral regimen comprising the nucleotide polymerase inhibitor sofosbuvir (SOF) with the NS5A inhibitor ledipasvir (LDV) or the NS5B non-nucleoside inhibitor GS-9669 in patients with genotype 1 hepatitis C virus (HCV) infection. Methods A total of 113 patients were enrolled. Sofosbuvir (400 mg once daily) and LDV (90 mg once daily) plus ribavirin (RBV) were given for 12 weeks to treatment-na{\"i}ve (TN) patients (n = 25) and those who did not respond to previous therapy (prior null responders, n = 9). Sofosbuvir and GS-9669 (500 mg once daily) plus RBV were given for 12 weeks to TN patients (n = 25) and prior null responders (n = 10). Additionally, prior null responders with cirrhosis were randomly assigned to groups given a fixed-dose combination of SOF and LDV, with RBV (n = 9) or without RBV (n = 10). Finally, a group of TN patients received SOF, LDV, and RBV for 6 weeks (n = 25). The primary efficacy end point was sustained virologic response 12 weeks after therapy (SVR12). Results SVR12 was achieved by 25 of 25 (100{\%}) TN patients receiving SOF, LDV, and RBV and 23 of 25 (92{\%}) of those receiving SOF, GS-9669, and RBV. Of TN patients receiving 6 weeks of SOF, LDV, and RBV, 17 of 25 (68{\%}) achieved SVR12. All noncirrhotic prior null responders receiving 12 weeks of SOF along with another direct-acting antiviral agent plus RBV achieved SVR12 - 9 of 9 (100{\%}) of those receiving SOF, LDV, and RBV and 10 of 10 (100{\%}) of those receiving SOF, GS-9669, and RBV. Among cirrhotic prior null responders, SVR12 was achieved by 9 (100{\%}) of those receiving SOF, LDV, and RBV and 7 (70{\%}) of those receiving SOF and LDVD without RBV. The most common reported adverse events were headache, fatigue, and nausea. Conclusions The combination of SOF and a second direct-acting antiviral agent is highly effective in TN patients with HCV genotype 1 infection and in patients that did not respond to previous treatment. ClinicalTrials.gov ID NCT01260350.",
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AU - Stedman, Catherine A.

AU - Hyland, Robert H.

AU - Ding, Xiao

AU - Svarovskaia, Evguenia

AU - Subramanian, G. Mani

AU - Symonds, William T.

AU - McHutchison, John G.

AU - Pang, Phillip S.

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N2 - Background & Aims We evaluated an all-oral regimen comprising the nucleotide polymerase inhibitor sofosbuvir (SOF) with the NS5A inhibitor ledipasvir (LDV) or the NS5B non-nucleoside inhibitor GS-9669 in patients with genotype 1 hepatitis C virus (HCV) infection. Methods A total of 113 patients were enrolled. Sofosbuvir (400 mg once daily) and LDV (90 mg once daily) plus ribavirin (RBV) were given for 12 weeks to treatment-naïve (TN) patients (n = 25) and those who did not respond to previous therapy (prior null responders, n = 9). Sofosbuvir and GS-9669 (500 mg once daily) plus RBV were given for 12 weeks to TN patients (n = 25) and prior null responders (n = 10). Additionally, prior null responders with cirrhosis were randomly assigned to groups given a fixed-dose combination of SOF and LDV, with RBV (n = 9) or without RBV (n = 10). Finally, a group of TN patients received SOF, LDV, and RBV for 6 weeks (n = 25). The primary efficacy end point was sustained virologic response 12 weeks after therapy (SVR12). Results SVR12 was achieved by 25 of 25 (100%) TN patients receiving SOF, LDV, and RBV and 23 of 25 (92%) of those receiving SOF, GS-9669, and RBV. Of TN patients receiving 6 weeks of SOF, LDV, and RBV, 17 of 25 (68%) achieved SVR12. All noncirrhotic prior null responders receiving 12 weeks of SOF along with another direct-acting antiviral agent plus RBV achieved SVR12 - 9 of 9 (100%) of those receiving SOF, LDV, and RBV and 10 of 10 (100%) of those receiving SOF, GS-9669, and RBV. Among cirrhotic prior null responders, SVR12 was achieved by 9 (100%) of those receiving SOF, LDV, and RBV and 7 (70%) of those receiving SOF and LDVD without RBV. The most common reported adverse events were headache, fatigue, and nausea. Conclusions The combination of SOF and a second direct-acting antiviral agent is highly effective in TN patients with HCV genotype 1 infection and in patients that did not respond to previous treatment. ClinicalTrials.gov ID NCT01260350.

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