Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection
Nezam Afdhal, K Rajender Reddy, David R Nelson, Eric Lawitz, Stuart C Gordon, Eugene Schiff, Ronald Nahass, Reem Ghalib, Norman Gitlin, Robert Herring, Jacob Lalezari, Ziad H Younes, Paul J Pockros, Adrian M Di Bisceglie, Sanjeev Arora, G Mani Subramanian, Yanni Zhu, Hadas Dvory-Sobol, Jenny C Yang, Phillip S Pang, William T Symonds, John G McHutchison, Andrew J Muir, Mark Sulkowski, Paul Kwo, ION-2 Investigators, Nezam Afdhal, Avanish Aggarwal, Sanjeev Arora, Leslie Bank, Kimberly Beavers, Nicholaos Bellos, Michael Bennett, David Bernstein, Thomas Boyer, Robert Brown Jr, Mario Chojkier, Christopher Christensen, James Cooper, Adrian Di Bisceglie, Richard Elion, Robert Emslie, Kyle Etzkorn, Gregory Everson, Steven Flamm, Todd Frederick, Bradley Freilich, Michael Galambos, Joseph Galati, Reem Ghalib, Norman Gitlin, Stuart Gordon, David Hassman, Trevor Hawkins, Robert Herring, Federico Hinestrosa, Charles Howell, Ira Jacobson, Marcelo Kugelmas, Paul Kwo, Jacob Lalezari, Eric Lawitz, Claudia Martorell, Anthony Mills, Ronald Nahass, David Nelson, Mindie Nguyen, Keyur Patel, Paul Pockros, Gary Poleynard, John Poterucha, John Poulos, David Pound, Ronald Pruitt, Bruce Rashbaum, Natarajan Ravendhran, K Rajender Reddy, Robert Reindollar, Peter Ruane, Vinod Rustgi, Michael Ryan, Eugene Schiff, Thomas Sepe, Aasim Sheikh, Mitchell Shiffman, Coleman Smith, Mark Sulkowski, Hugo Vargas, Kimberly Workowski, David Wyles, Ziad Younes, Nezam Afdhal, K Rajender Reddy, David R Nelson, Eric Lawitz, Stuart C Gordon, Eugene Schiff, Ronald Nahass, Reem Ghalib, Norman Gitlin, Robert Herring, Jacob Lalezari, Ziad H Younes, Paul J Pockros, Adrian M Di Bisceglie, Sanjeev Arora, G Mani Subramanian, Yanni Zhu, Hadas Dvory-Sobol, Jenny C Yang, Phillip S Pang, William T Symonds, John G McHutchison, Andrew J Muir, Mark Sulkowski, Paul Kwo, ION-2 Investigators, Nezam Afdhal, Avanish Aggarwal, Sanjeev Arora, Leslie Bank, Kimberly Beavers, Nicholaos Bellos, Michael Bennett, David Bernstein, Thomas Boyer, Robert Brown Jr, Mario Chojkier, Christopher Christensen, James Cooper, Adrian Di Bisceglie, Richard Elion, Robert Emslie, Kyle Etzkorn, Gregory Everson, Steven Flamm, Todd Frederick, Bradley Freilich, Michael Galambos, Joseph Galati, Reem Ghalib, Norman Gitlin, Stuart Gordon, David Hassman, Trevor Hawkins, Robert Herring, Federico Hinestrosa, Charles Howell, Ira Jacobson, Marcelo Kugelmas, Paul Kwo, Jacob Lalezari, Eric Lawitz, Claudia Martorell, Anthony Mills, Ronald Nahass, David Nelson, Mindie Nguyen, Keyur Patel, Paul Pockros, Gary Poleynard, John Poterucha, John Poulos, David Pound, Ronald Pruitt, Bruce Rashbaum, Natarajan Ravendhran, K Rajender Reddy, Robert Reindollar, Peter Ruane, Vinod Rustgi, Michael Ryan, Eugene Schiff, Thomas Sepe, Aasim Sheikh, Mitchell Shiffman, Coleman Smith, Mark Sulkowski, Hugo Vargas, Kimberly Workowski, David Wyles, Ziad Younes
Abstract
Background: Effective treatment for hepatitis C virus (HCV) genotype 1 infection in patients who have not had a sustained virologic response to prior interferon-based therapy represents an unmet medical need.
Methods: We conducted a phase 3, randomized, open-label study involving patients infected with HCV genotype 1 who had not had a sustained virologic response after treatment with peginterferon and ribavirin, with or without a protease inhibitor. Patients were randomly assigned to receive the NS5A inhibitor ledipasvir and the nucleotide polymerase inhibitor sofosbuvir in a once-daily, fixed-dose combination tablet 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: Among the 440 patients who underwent randomization and were treated, 20% had cirrhosis and 79% had HCV genotype 1a infection. The rates of sustained virologic response were high in all treatment groups: 94% (95% confidence interval [CI], 87 to 97) in the group that received 12 weeks of ledipasvir-sofosbuvir; 96% (95% CI, 91 to 99) in the group that received 12 weeks of ledipasvir-sofosbuvir and ribavirin; 99% (95% CI, 95 to 100) in the group that received 24 weeks of ledipasvir-sofosbuvir; and 99% (95% CI, 95 to 100) in the group that received 24 weeks of ledipasvir-sofosbuvir and ribavirin. No patient discontinued treatment owing to an adverse event. The most common adverse events were fatigue, headache, and nausea.
Conclusions: Treatment with a once-daily, single-tablet regimen of ledipasvir and sofosbuvir resulted in high rates of sustained virologic response among patients with HCV genotype 1 infection who had not had a sustained virologic response to prior interferon-based treatment. (Funded by Gilead Sciences; ION-2 ClinicalTrials.gov number, NCT01768286.).
Source: PubMed