Sofosbuvir, Velpatasvir, and Voxilaprevir for Previously Treated HCV Infection
Marc Bourlière, Stuart C Gordon, Steven L Flamm, Curtis L Cooper, Alnoor Ramji, Myron Tong, Natarajan Ravendhran, John M Vierling, Tram T Tran, Stephen Pianko, Meena B Bansal, Victor de Lédinghen, Robert H Hyland, Luisa M Stamm, Hadas Dvory-Sobol, Evguenia Svarovskaia, Jie Zhang, K C Huang, G Mani Subramanian, Diana M Brainard, John G McHutchison, Elizabeth C Verna, Peter Buggisch, Charles S Landis, Ziad H Younes, Michael P Curry, Simone I Strasser, Eugene R Schiff, K Rajender Reddy, Michael P Manns, Kris V Kowdley, Stefan Zeuzem, POLARIS-1 and POLARIS-4 Investigators, Stuart Roberts, Gregory Dore, Barbara Leggett, Alexander Thompson, Stephen Shafran, Brian Conway, Bernard Willems, Jordan Feld, Sergio Borgia, Stephen Congly, Stanislas Pol, Didier Samuel, Danielle Botta-Fridlund, Ghassan Riachi, Christophe Hezode, Fabien Zoulim, Jean-Pierre Bronowicki, François Habersetzer, Philippe Mathurin, Dominique Guyader, Jean-Didier Grange, Véronique Loustaud-Ratti, Vlad Ratziu, Lawrence Serfaty, Albert Tran, Dominique Larrey, Laurent Alric, Tarik Asselah, Armando Abergel, Vincent Leroy, Sophie Metivier, Thomas Berg, Tobias Goeser, Ulrich Spengler, Edward Gane, Catherine A M Stedman, Grissel Ortiz-Lasanta, Stephen Ryder, Graham Foster, Ashley Brown, Kosh Agarwal, Andrew Ustianowski, Richard Aspinall, Adrian Di Bisceglie, Mitchell Shiffman, Peter Ruane, Michael Bennett, Anna Patel, Anna Lok, Sergio Rojter, Michael Charlton, Lisa Nyberg, Raymond Chung, Marco Lacerda, Coleman Smith, Mandana Khalili, Raymond Rubin, William Smith, Gregory Everson, Mark Sulkowski, James Levin, Norman Gitlin, Kimberly Workowski, Ronald Nahass, Michael Ryan, Eric Lawitz, Arun Sanyal, Mindie Nguyen, Giuseppe Morelli, Bradley Freilich, Marcelo Kugelmas, Aasim Sheikh, Thomas Sepe, Mitchell Davis, David Pound, Constance Benson, Federico Hinestrosa, Norbert Brau, Robert Herring, Timothy Morgan, Zeid Kayali, Mordechai Rabinovitz, James Cooper, Brian Pearlman, Obaid Shaikh, William Harlan, Ritu Agarwal, Marc Bourliere, Véronique Loustaud Ratti, Grisell Ortiz-Lasanta, Jane Collier, Daniel Forton, Sonal Kumar, lan WeisbergI, Bal Raj Bhandari, John Poulos, Shyamasundaran Kottilil, Marc Bourlière, Stuart C Gordon, Steven L Flamm, Curtis L Cooper, Alnoor Ramji, Myron Tong, Natarajan Ravendhran, John M Vierling, Tram T Tran, Stephen Pianko, Meena B Bansal, Victor de Lédinghen, Robert H Hyland, Luisa M Stamm, Hadas Dvory-Sobol, Evguenia Svarovskaia, Jie Zhang, K C Huang, G Mani Subramanian, Diana M Brainard, John G McHutchison, Elizabeth C Verna, Peter Buggisch, Charles S Landis, Ziad H Younes, Michael P Curry, Simone I Strasser, Eugene R Schiff, K Rajender Reddy, Michael P Manns, Kris V Kowdley, Stefan Zeuzem, POLARIS-1 and POLARIS-4 Investigators, Stuart Roberts, Gregory Dore, Barbara Leggett, Alexander Thompson, Stephen Shafran, Brian Conway, Bernard Willems, Jordan Feld, Sergio Borgia, Stephen Congly, Stanislas Pol, Didier Samuel, Danielle Botta-Fridlund, Ghassan Riachi, Christophe Hezode, Fabien Zoulim, Jean-Pierre Bronowicki, François Habersetzer, Philippe Mathurin, Dominique Guyader, Jean-Didier Grange, Véronique Loustaud-Ratti, Vlad Ratziu, Lawrence Serfaty, Albert Tran, Dominique Larrey, Laurent Alric, Tarik Asselah, Armando Abergel, Vincent Leroy, Sophie Metivier, Thomas Berg, Tobias Goeser, Ulrich Spengler, Edward Gane, Catherine A M Stedman, Grissel Ortiz-Lasanta, Stephen Ryder, Graham Foster, Ashley Brown, Kosh Agarwal, Andrew Ustianowski, Richard Aspinall, Adrian Di Bisceglie, Mitchell Shiffman, Peter Ruane, Michael Bennett, Anna Patel, Anna Lok, Sergio Rojter, Michael Charlton, Lisa Nyberg, Raymond Chung, Marco Lacerda, Coleman Smith, Mandana Khalili, Raymond Rubin, William Smith, Gregory Everson, Mark Sulkowski, James Levin, Norman Gitlin, Kimberly Workowski, Ronald Nahass, Michael Ryan, Eric Lawitz, Arun Sanyal, Mindie Nguyen, Giuseppe Morelli, Bradley Freilich, Marcelo Kugelmas, Aasim Sheikh, Thomas Sepe, Mitchell Davis, David Pound, Constance Benson, Federico Hinestrosa, Norbert Brau, Robert Herring, Timothy Morgan, Zeid Kayali, Mordechai Rabinovitz, James Cooper, Brian Pearlman, Obaid Shaikh, William Harlan, Ritu Agarwal, Marc Bourliere, Véronique Loustaud Ratti, Grisell Ortiz-Lasanta, Jane Collier, Daniel Forton, Sonal Kumar, lan WeisbergI, Bal Raj Bhandari, John Poulos, Shyamasundaran Kottilil
Abstract
Background: Patients who are chronically infected with hepatitis C virus (HCV) and who do not have a sustained virologic response after treatment with regimens containing direct-acting antiviral agents (DAAs) have limited retreatment options.
Methods: We conducted two phase 3 trials involving patients who had been previously treated with a DAA-containing regimen. In POLARIS-1, patients with HCV genotype 1 infection who had previously received a regimen containing an NS5A inhibitor were randomly assigned in a 1:1 ratio to receive either the nucleotide polymerase inhibitor sofosbuvir, the NS5A inhibitor velpatasvir, and the protease inhibitor voxilaprevir (150 patients) or matching placebo (150 patients) once daily for 12 weeks. Patients who were infected with HCV of other genotypes (114 patients) were enrolled in the sofosbuvir-velpatasvir-voxilaprevir group. In POLARIS-4, patients with HCV genotype 1, 2, or 3 infection who had previously received a DAA regimen but not an NS5A inhibitor were randomly assigned in a 1:1 ratio to receive sofosbuvir-velpatasvir-voxilaprevir (163 patients) or sofosbuvir-velpatasvir (151 patients) for 12 weeks. An additional 19 patients with HCV genotype 4 infection were enrolled in the sofosbuvir-velpatasvir-voxilaprevir group.
Results: In the three active-treatment groups, 46% of the patients had compensated cirrhosis. In POLARIS-1, the rate of sustained virologic response was 96% with sofosbuvir-velpatasvir-voxilaprevir, as compared with 0% with placebo. In POLARIS-4, the rate of response was 98% with sofosbuvir-velpatasvir-voxilaprevir and 90% with sofosbuvir-velpatasvir. The most common adverse events were headache, fatigue, diarrhea, and nausea. In the active-treatment groups in both trials, the percentage of patients who discontinued treatment owing to adverse events was 1% or lower.
Conclusions: Sofosbuvir-velpatasvir-voxilaprevir taken for 12 weeks provided high rates of sustained virologic response among patients across HCV genotypes in whom treatment with a DAA regimen had previously failed. (Funded by Gilead Sciences; POLARIS-1 and POLARIS-4 ClinicalTrials.gov numbers, NCT02607735 and NCT02639247 .).
Source: PubMed