Sofosbuvir and Velpatasvir for HCV Genotype 1, 2, 4, 5, and 6 Infection
Jordan J Feld, Ira M Jacobson, Christophe Hézode, Tarik Asselah, Peter J Ruane, Norbert Gruener, Armand Abergel, Alessandra Mangia, Ching-Lung Lai, Henry L Y Chan, Francesco Mazzotta, Christophe Moreno, Eric Yoshida, Stephen D Shafran, William J Towner, Tram T Tran, John McNally, Anu Osinusi, Evguenia Svarovskaia, Yanni Zhu, Diana M Brainard, John G McHutchison, Kosh Agarwal, Stefan Zeuzem, ASTRAL-1 Investigators, Stefan Bourgeois, Christophe George, Christophe Moreno, Jordan Feld, Stephen Shafran, Eric Yoshida, Brian Conway, Curtis Cooper, Bernard Willems, Mark Swain, Tarik Asselah, Stanislas Pol, Phillipe Mathurin, Didier Samuel, Armand Abergel, Marc Bourlière, Christophe Hézode, Victor De Ledinghen, Véronique Loustaud-Ratti, Laurent Alric, Fabien Zoulim, Stefan Zeuzem, Norbert Grüner, Keikawus Arastéh, Tobias Goeser, Thomas Berg, Guido Gerken, Jorg Petersen, Stefan Mauss, Michael P Manns, Ching-Lung Lai, Henry Lik-Yuen Chan, Alessandra Mangia, Francesco Mazzotta, Kosh Agarwal, Richard Aspinall, Ashley Brown, Graham Foster, Jane Collier, William Malcolm Charles Rosenberg, Mathew Cramp, Ray Fox, Stephen Ryder, Andrew Ustianowski, Dan Forton, Peter J Ruane, Tram Tran, Norman Gitlin, Nezam H Afdhal, William J Towner, Giuseppe Morelli, Mindie Nguyen, Lisa Nyberg, Mordechai Rabinovitz, Aasim Sheikh, Mitchell L Shiffman, Kimberly Workowski, Norbert Braü, Mitchell Davis, Stuart C Gordon, Robert Herring, Federico Hinestrosa, Eric Lawitz, Timothy Morgan, K Rajender Reddy, Eugene R Schiff, Paul J Thuluvath, Ziad Younes, Michael T Bennett, Kyle Etzkorn, Greg Everson, David Pound, Maribel Rodriguez-Torres, Thomas Sepe, Mark Sulkowski, Stuart Cohen, Ira Jacobson, Michael M Ryan, Steve Flamm, Obaid Shaikh, Curt Hagedorn, Jordan J Feld, Ira M Jacobson, Christophe Hézode, Tarik Asselah, Peter J Ruane, Norbert Gruener, Armand Abergel, Alessandra Mangia, Ching-Lung Lai, Henry L Y Chan, Francesco Mazzotta, Christophe Moreno, Eric Yoshida, Stephen D Shafran, William J Towner, Tram T Tran, John McNally, Anu Osinusi, Evguenia Svarovskaia, Yanni Zhu, Diana M Brainard, John G McHutchison, Kosh Agarwal, Stefan Zeuzem, ASTRAL-1 Investigators, Stefan Bourgeois, Christophe George, Christophe Moreno, Jordan Feld, Stephen Shafran, Eric Yoshida, Brian Conway, Curtis Cooper, Bernard Willems, Mark Swain, Tarik Asselah, Stanislas Pol, Phillipe Mathurin, Didier Samuel, Armand Abergel, Marc Bourlière, Christophe Hézode, Victor De Ledinghen, Véronique Loustaud-Ratti, Laurent Alric, Fabien Zoulim, Stefan Zeuzem, Norbert Grüner, Keikawus Arastéh, Tobias Goeser, Thomas Berg, Guido Gerken, Jorg Petersen, Stefan Mauss, Michael P Manns, Ching-Lung Lai, Henry Lik-Yuen Chan, Alessandra Mangia, Francesco Mazzotta, Kosh Agarwal, Richard Aspinall, Ashley Brown, Graham Foster, Jane Collier, William Malcolm Charles Rosenberg, Mathew Cramp, Ray Fox, Stephen Ryder, Andrew Ustianowski, Dan Forton, Peter J Ruane, Tram Tran, Norman Gitlin, Nezam H Afdhal, William J Towner, Giuseppe Morelli, Mindie Nguyen, Lisa Nyberg, Mordechai Rabinovitz, Aasim Sheikh, Mitchell L Shiffman, Kimberly Workowski, Norbert Braü, Mitchell Davis, Stuart C Gordon, Robert Herring, Federico Hinestrosa, Eric Lawitz, Timothy Morgan, K Rajender Reddy, Eugene R Schiff, Paul J Thuluvath, Ziad Younes, Michael T Bennett, Kyle Etzkorn, Greg Everson, David Pound, Maribel Rodriguez-Torres, Thomas Sepe, Mark Sulkowski, Stuart Cohen, Ira Jacobson, Michael M Ryan, Steve Flamm, Obaid Shaikh, Curt Hagedorn
Abstract
Background: A simple treatment regimen that is effective in a broad range of patients who are chronically infected with the hepatitis C virus (HCV) remains an unmet medical need.
Methods: We conducted a phase 3, double-blind, placebo-controlled study involving untreated and previously treated patients with chronic HCV genotype 1, 2, 4, 5, or 6 infection, including those with compensated cirrhosis. Patients with HCV genotype 1, 2, 4, or 6 were randomly assigned in a 5:1 ratio to receive the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor velpatasvir in a once-daily, fixed-dose combination tablet or matching placebo for 12 weeks. Because of the low prevalence of genotype 5 in the study regions, patients with genotype 5 did not undergo randomization but were assigned to the sofosbuvir-velpatasvir group. The primary end point was a sustained virologic response at 12 weeks after the end of therapy.
Results: Of the 624 patients who received treatment with sofosbuvir-velpatasvir, 34% had HCV genotype 1a, 19% genotype 1b, 17% genotype 2, 19% genotype 4, 6% genotype 5, and 7% genotype 6. A total of 8% of patients were black, 19% had cirrhosis, and 32% had been previously treated for HCV. The rate of sustained virologic response among patients receiving sofosbuvir-velpatasvir was 99% (95% confidence interval, 98 to >99). Two patients receiving sofosbuvir-velpatasvir, both with HCV genotype 1, had a virologic relapse. None of the 116 patients receiving placebo had a sustained virologic response. Serious adverse events were reported in 15 patients (2%) in the sofosbuvir-velpatasvir group and none in the placebo group.
Conclusions: Once-daily sofosbuvir-velpatasvir for 12 weeks provided high rates of sustained virologic response among both previously treated and untreated patients infected with HCV genotype 1, 2, 4, 5, or 6, including those with compensated cirrhosis. (Funded by Gilead Sciences; ClinicalTrials.gov number, NCT02201940.).
Source: PubMed