Sofosbuvir and Velpatasvir for HCV Genotype 2 and 3 Infection
Graham R Foster, Nezam Afdhal, Stuart K Roberts, Norbert Bräu, Edward J Gane, Stephen Pianko, Eric Lawitz, Alex Thompson, Mitchell L Shiffman, Curtis Cooper, William J Towner, Brian Conway, Peter Ruane, Marc Bourlière, Tarik Asselah, Thomas Berg, Stefan Zeuzem, William Rosenberg, Kosh Agarwal, Catherine A M Stedman, Hongmei Mo, Hadas Dvory-Sobol, Lingling Han, Jing Wang, John McNally, Anu Osinusi, Diana M Brainard, John G McHutchison, Francesco Mazzotta, Tram T Tran, Stuart C Gordon, Keyur Patel, Nancy Reau, Alessandra Mangia, Mark Sulkowski, ASTRAL-2 Investigators, ASTRAL-3 Investigators, Nezam Afdhal, Ritu Agarwal, M Tarek Al-Assi, Michael Bennett, David Bernstein, Raj Bhandari, Norbert Bräu, Stuart Cohen, Mitchell Davis, Adrian Di Bisceglie, Kyle Etzkorn, Gregory Everson, Jeffrey Fessel, Steven Flamm, Reem Ghalib, Norm Gitlin, Elliot Godofsky, Stuart Gordon, William Harlan, Trevor Hawkins, Robert Herring, Federico Hinestrosa, Ira Jacobson, Eric Lawitz, Anne Luetkemeyer, Giuseppe Morelli, Timothy Morgan, Anders Nyberg, Neville Pimstone, David Pound, Nancy Reau, Rajender Reddy, Maribel Rodriguez-Torres, Sergio Rotjer, Peter Ruane, Vinod Rustgi, Michael Ryan, Arun Sanyal, Eugene Schiff, Thomas Sepe, Obaid Shaikh, Aasim Sheikh, Mitchell Shiffman, Mark Sulkowski, Paul Thuluvath, Myron Tong, William Towner, Tram Tran, Kimberly Workowski, David Wyles, Ziad Younes, Wendy Cheng, Greg Dore, Barbara Leggett, Lindsay Mollison, Stephen Pianko, Stuart Roberts, Simone Strasser, Alexander Thompson, Brian Conway, Curtis Cooper, Jordan Feld, Stephen Shafran, Mark Swain, Bernard Willems, Eric Yoshida, Armand Abergel, Laurent Alric, Tarik Asselah, Marc Bourlière, Victor De Ledinghen, Christophe Hézode, Véronique Loustaud-Ratti, Philippe Mathurin, Stanislas Pol, Didier Samuel, Fabien Zoulim, Keikawus Arastéh, Thomas Berg, Guido Gerken, Tobias Goeser, Norbert Gruener, Michael Manns, Stefan Mauss, Jorg Petersen, Stefan Zeuzem, Alessandra Mangia, Francesco Mazzotta, Edward Gane, Catherine Stedman, Kosh Agarwal, Richard Aspinall, Ashley Brown, Jane Collier, Matthew Cramp, Daniel Forton, Graham Foster, Ray Fox, William Rosenberg, Stephen Ryder, Andrew Ustianowski, Nezam Afdhal, Michael Bennett, Norbert Bräu, Stuart Cohen, Mitchell Davis, Kyle Etzkorn, Gregory Everson, Steven Flamm, Stuart Gordon, Federico Hinestrosa, Ira Jacobson, Eric Lawitz, Giuseppe Morelli, Keyur Patel, David Pound, K Rajender Reddy, Maribel Rodriguez-Torres, Michael Ryan, Eugene Schiff, Obaid Shaikh, Aasim Sheikh, Mitchell Shiffman, Mark Sulkowski, William Towner, Tram Tran, Ziad Younes, Graham R Foster, Nezam Afdhal, Stuart K Roberts, Norbert Bräu, Edward J Gane, Stephen Pianko, Eric Lawitz, Alex Thompson, Mitchell L Shiffman, Curtis Cooper, William J Towner, Brian Conway, Peter Ruane, Marc Bourlière, Tarik Asselah, Thomas Berg, Stefan Zeuzem, William Rosenberg, Kosh Agarwal, Catherine A M Stedman, Hongmei Mo, Hadas Dvory-Sobol, Lingling Han, Jing Wang, John McNally, Anu Osinusi, Diana M Brainard, John G McHutchison, Francesco Mazzotta, Tram T Tran, Stuart C Gordon, Keyur Patel, Nancy Reau, Alessandra Mangia, Mark Sulkowski, ASTRAL-2 Investigators, ASTRAL-3 Investigators, Nezam Afdhal, Ritu Agarwal, M Tarek Al-Assi, Michael Bennett, David Bernstein, Raj Bhandari, Norbert Bräu, Stuart Cohen, Mitchell Davis, Adrian Di Bisceglie, Kyle Etzkorn, Gregory Everson, Jeffrey Fessel, Steven Flamm, Reem Ghalib, Norm Gitlin, Elliot Godofsky, Stuart Gordon, William Harlan, Trevor Hawkins, Robert Herring, Federico Hinestrosa, Ira Jacobson, Eric Lawitz, Anne Luetkemeyer, Giuseppe Morelli, Timothy Morgan, Anders Nyberg, Neville Pimstone, David Pound, Nancy Reau, Rajender Reddy, Maribel Rodriguez-Torres, Sergio Rotjer, Peter Ruane, Vinod Rustgi, Michael Ryan, Arun Sanyal, Eugene Schiff, Thomas Sepe, Obaid Shaikh, Aasim Sheikh, Mitchell Shiffman, Mark Sulkowski, Paul Thuluvath, Myron Tong, William Towner, Tram Tran, Kimberly Workowski, David Wyles, Ziad Younes, Wendy Cheng, Greg Dore, Barbara Leggett, Lindsay Mollison, Stephen Pianko, Stuart Roberts, Simone Strasser, Alexander Thompson, Brian Conway, Curtis Cooper, Jordan Feld, Stephen Shafran, Mark Swain, Bernard Willems, Eric Yoshida, Armand Abergel, Laurent Alric, Tarik Asselah, Marc Bourlière, Victor De Ledinghen, Christophe Hézode, Véronique Loustaud-Ratti, Philippe Mathurin, Stanislas Pol, Didier Samuel, Fabien Zoulim, Keikawus Arastéh, Thomas Berg, Guido Gerken, Tobias Goeser, Norbert Gruener, Michael Manns, Stefan Mauss, Jorg Petersen, Stefan Zeuzem, Alessandra Mangia, Francesco Mazzotta, Edward Gane, Catherine Stedman, Kosh Agarwal, Richard Aspinall, Ashley Brown, Jane Collier, Matthew Cramp, Daniel Forton, Graham Foster, Ray Fox, William Rosenberg, Stephen Ryder, Andrew Ustianowski, Nezam Afdhal, Michael Bennett, Norbert Bräu, Stuart Cohen, Mitchell Davis, Kyle Etzkorn, Gregory Everson, Steven Flamm, Stuart Gordon, Federico Hinestrosa, Ira Jacobson, Eric Lawitz, Giuseppe Morelli, Keyur Patel, David Pound, K Rajender Reddy, Maribel Rodriguez-Torres, Michael Ryan, Eugene Schiff, Obaid Shaikh, Aasim Sheikh, Mitchell Shiffman, Mark Sulkowski, William Towner, Tram Tran, Ziad Younes
Abstract
Background: In phase 2 trials, treatment with the combination of the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor velpatasvir resulted in high rates of sustained virologic response in patients chronically infected with hepatitis C virus (HCV) genotype 2 or 3.
Methods: We conducted two randomized, phase 3, open-label studies involving patients who had received previous treatment for HCV genotype 2 or 3 and those who had not received such treatment, including patients with compensated cirrhosis. In one trial, patients with HCV genotype 2 were randomly assigned in a 1:1 ratio to receive sofosbuvir-velpatasvir, in a once-daily, fixed-dose combination tablet (134 patients), or sofosbuvir plus weight-based ribavirin (132 patients) for 12 weeks. In a second trial, patients with HCV genotype 3 were randomly assigned in a 1:1 ratio to receive sofosbuvir-velpatasvir for 12 weeks (277 patients) or sofosbuvir-ribavirin for 24 weeks (275 patients). The primary end point for the two trials was a sustained virologic response at 12 weeks after the end of therapy.
Results: Among patients with HCV genotype 2, the rate of sustained virologic response in the sofosbuvir-velpatasvir group was 99% (95% confidence interval [CI], 96 to 100), which was superior to the rate of 94% (95% CI, 88 to 97) in the sofosbuvir-ribavirin group (P=0.02). Among patients with HCV genotype 3, the rate of sustained virologic response in the sofosbuvir-velpatasvir group was 95% (95% CI, 92 to 98), which was superior to the rate of 80% (95% CI, 75 to 85) in the sofosbuvir-ribavirin group (P<0.001). The most common adverse events in the two studies were fatigue, headache, nausea, and insomnia.
Conclusions: Among patients with HCV genotype 2 or 3 with or without previous treatment, including those with compensated cirrhosis, 12 weeks of treatment with sofosbuvir-velpatasvir resulted in rates of sustained virologic response that were superior to those with standard treatment with sofosbuvir-ribavirin. (Funded by Gilead Sciences; ASTRAL-2 ClinicalTrials.gov number, NCT02220998; and ASTRAL-3, NCT02201953.).
Source: PubMed