Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection
Nezam Afdhal, Stefan Zeuzem, Paul Kwo, Mario Chojkier, Norman Gitlin, Massimo Puoti, Manuel Romero-Gomez, Jean-Pierre Zarski, Kosh Agarwal, Peter Buggisch, Graham R Foster, Norbert Bräu, Maria Buti, Ira M Jacobson, G Mani Subramanian, Xiao Ding, Hongmei Mo, Jenny C Yang, Phillip S Pang, William T Symonds, John G McHutchison, Andrew J Muir, Alessandra Mangia, Patrick Marcellin, ION-1 Investigators, Marc Bourlière, Jean-Pierre Bronowicki, Christophe Hézode, Patrick Marcellin, Vlad Ratziu, Lawrence Serfaty, Jean-Pierre Zarski, Thomas Berg, Peter Buggisch, Peter Galle, Guido Gerken, Tobias Goeser, Ansgar Lohse, Stefan Mauss, Robert Thimme, Hans Wedemeyer, Stefan Zeuzem, Alfredo Alberti, Pietro Andreone, Mario Angelico, Massimo Colombo, Antonio Craxì, Alessandra Mangia, Massimo Puoti, Mario Rizzetto, Maribel Rodriguez-Torres, Raúl Andrade, Maria Buti, Javier Crespo, Xavier Forns, Javier García-Samaniego, Manuel Romero-Gomez, Kosh Agarwal, Ashley Brown, Matthew Cramp, Geoffrey Dusheiko, Graham Foster, David Mutimer, Andrew Ustianowski, Nezam Afdhal, Christopher Albers, Sanjeev Arora, Kimberly Beavers, Michael Bennett, David Bernstein, Norbert Bräu, Robert Brown Jr, Mario Chojkier, Raymond Chung, James Cooper, Mitchell Davis, Adrian Di Bisceglie, Robin Dretler, Richard Elion, Gregory Everson, Steven Flamm, Bradley Freilich, Michael Fried, Joseph Galati, Reem Ghalib, Norman Gitlin, Stuart Gordon, Steven-Huy Han, Trevor Hawkins, Robert Herring, Federico Hinestrosa, Ira Jacobson, Lennox Jeffers, Kris Kowdley, Marcelo Kugelmas, Paul Kwo, Eric Lawitz, William Lee, Timothy Morgan, Ronald Nahass, David Nelson, Mindie Nguyen, Keyur Patel, Paul Pockros, Gary Poleynard, John Poterucha, John Poulos, David Pound, Ronald Pruitt, Natarajan Ravendhran, K Rajender Reddy, Robert Reindollar, Lorenzo Rossaro, Peter Ruane, Vinod Rustgi, Michael Ryan, Michael Saag, Eugene Schiff, Aasim Sheikh, Mitchell Shiffman, Coleman Smith, Mark Sulkowski, Kimberly Workowski, Ziad Younes, Nezam Afdhal, Stefan Zeuzem, Paul Kwo, Mario Chojkier, Norman Gitlin, Massimo Puoti, Manuel Romero-Gomez, Jean-Pierre Zarski, Kosh Agarwal, Peter Buggisch, Graham R Foster, Norbert Bräu, Maria Buti, Ira M Jacobson, G Mani Subramanian, Xiao Ding, Hongmei Mo, Jenny C Yang, Phillip S Pang, William T Symonds, John G McHutchison, Andrew J Muir, Alessandra Mangia, Patrick Marcellin, ION-1 Investigators, Marc Bourlière, Jean-Pierre Bronowicki, Christophe Hézode, Patrick Marcellin, Vlad Ratziu, Lawrence Serfaty, Jean-Pierre Zarski, Thomas Berg, Peter Buggisch, Peter Galle, Guido Gerken, Tobias Goeser, Ansgar Lohse, Stefan Mauss, Robert Thimme, Hans Wedemeyer, Stefan Zeuzem, Alfredo Alberti, Pietro Andreone, Mario Angelico, Massimo Colombo, Antonio Craxì, Alessandra Mangia, Massimo Puoti, Mario Rizzetto, Maribel Rodriguez-Torres, Raúl Andrade, Maria Buti, Javier Crespo, Xavier Forns, Javier García-Samaniego, Manuel Romero-Gomez, Kosh Agarwal, Ashley Brown, Matthew Cramp, Geoffrey Dusheiko, Graham Foster, David Mutimer, Andrew Ustianowski, Nezam Afdhal, Christopher Albers, Sanjeev Arora, Kimberly Beavers, Michael Bennett, David Bernstein, Norbert Bräu, Robert Brown Jr, Mario Chojkier, Raymond Chung, James Cooper, Mitchell Davis, Adrian Di Bisceglie, Robin Dretler, Richard Elion, Gregory Everson, Steven Flamm, Bradley Freilich, Michael Fried, Joseph Galati, Reem Ghalib, Norman Gitlin, Stuart Gordon, Steven-Huy Han, Trevor Hawkins, Robert Herring, Federico Hinestrosa, Ira Jacobson, Lennox Jeffers, Kris Kowdley, Marcelo Kugelmas, Paul Kwo, Eric Lawitz, William Lee, Timothy Morgan, Ronald Nahass, David Nelson, Mindie Nguyen, Keyur Patel, Paul Pockros, Gary Poleynard, John Poterucha, John Poulos, David Pound, Ronald Pruitt, Natarajan Ravendhran, K Rajender Reddy, Robert Reindollar, Lorenzo Rossaro, Peter Ruane, Vinod Rustgi, Michael Ryan, Michael Saag, Eugene Schiff, Aasim Sheikh, Mitchell Shiffman, Coleman Smith, Mark Sulkowski, Kimberly Workowski, Ziad Younes
Abstract
Background: In phase 2 studies, treatment with the all-oral combination of the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor ledipasvir resulted in high rates of sustained virologic response among previously untreated patients with hepatitis C virus (HCV) genotype 1 infection.
Methods: We conducted a phase 3, open-label study involving previously untreated patients with chronic HCV genotype 1 infection. Patients were randomly assigned in a 1:1:1:1 ratio to receive ledipasvir and sofosbuvir in a fixed-dose combination tablet once daily for 12 weeks, ledipasvir-sofosbuvir plus ribavirin for 12 weeks, ledipasvir-sofosbuvir for 24 weeks, or ledipasvir-sofosbuvir plus ribavirin for 24 weeks. The primary end point was a sustained virologic response at 12 weeks after the end of therapy.
Results: Of the 865 patients who underwent randomization and were treated, 16% had cirrhosis, 12% were black, and 67% had HCV genotype 1a infection. The rates of sustained virologic response were 99% (95% confidence interval [CI], 96 to 100) in the group that received 12 weeks of ledipasvir-sofosbuvir; 97% (95% CI, 94 to 99) in the group that received 12 weeks of ledipasvir-sofosbuvir plus ribavirin; 98% (95% CI, 95 to 99) in the group that received 24 weeks of ledipasvir-sofosbuvir; and 99% (95% CI, 97 to 100) in the group that received 24 weeks of ledipasvir-sofosbuvir plus ribavirin. No patient in either 12-week group discontinued ledipasvir-sofosbuvir owing to an adverse event. The most common adverse events were fatigue, headache, insomnia, and nausea.
Conclusions: Once-daily ledipasvir-sofosbuvir with or without ribavirin for 12 or 24 weeks was highly effective in previously untreated patients with HCV genotype 1 infection. (Funded by Gilead Sciences; ION-1 ClinicalTrials.gov number NCT01701401.).
Source: PubMed