Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options
Ira M Jacobson, Stuart C Gordon, Kris V Kowdley, Eric M Yoshida, Maribel Rodriguez-Torres, Mark S Sulkowski, Mitchell L Shiffman, Eric Lawitz, Gregory Everson, Michael Bennett, Eugene Schiff, M Tarek Al-Assi, G Mani Subramanian, Di An, Ming Lin, John McNally, Diana Brainard, William T Symonds, John G McHutchison, Keyur Patel, Jordan Feld, Stephen Pianko, David R Nelson, POSITRON Study, FUSION Study, Jacob George, Barbara Leggett, Stephen Pianko, Alexander Thompson, Magdy Elkashab, Alnoor Ramji, Mark Swain, Bernard Willems, Eric Yoshida, Edward Gane, Catherine Stedman, Nezam Afdhal, Avanish Aggarwal, Leslie Bank, Kimberly Beavers, Michael Bennett, Raymond Chung, Mitchell Davis, Richard Elion, Kyle Etzkorn, Gregory Everson, Bradley Freilich, Michael Galambos, Stuart Gordon, Tarek Hassanein, Robert Herring Jr, Federico Hinestrosa, Ira Jacobson, Kris Kowdley, Marcelo Kugelmas, Jay Lalezari, Eric Lawitz, Claudia Martorell, Anthony Mills, Giuseppe Morelli, Ronald Nahass, Anders Nyberg, Ponni Perumalswami, Gary Poleynard, K Rajender Reddy, Maribel Roderiguez-Torres, Peter Ruane, Vinod Rustgi, Michael Ryan, Michael Saag, Eugene Schiff, Thomas Sepe, Aasim Sheikh, Mitchell Shiffman, Coleman Smith, Mark Sulkowski, David Wyles, Ziad Younes, Zobair Younossi, Ira M Jacobson, Stuart C Gordon, Kris V Kowdley, Eric M Yoshida, Maribel Rodriguez-Torres, Mark S Sulkowski, Mitchell L Shiffman, Eric Lawitz, Gregory Everson, Michael Bennett, Eugene Schiff, M Tarek Al-Assi, G Mani Subramanian, Di An, Ming Lin, John McNally, Diana Brainard, William T Symonds, John G McHutchison, Keyur Patel, Jordan Feld, Stephen Pianko, David R Nelson, POSITRON Study, FUSION Study, Jacob George, Barbara Leggett, Stephen Pianko, Alexander Thompson, Magdy Elkashab, Alnoor Ramji, Mark Swain, Bernard Willems, Eric Yoshida, Edward Gane, Catherine Stedman, Nezam Afdhal, Avanish Aggarwal, Leslie Bank, Kimberly Beavers, Michael Bennett, Raymond Chung, Mitchell Davis, Richard Elion, Kyle Etzkorn, Gregory Everson, Bradley Freilich, Michael Galambos, Stuart Gordon, Tarek Hassanein, Robert Herring Jr, Federico Hinestrosa, Ira Jacobson, Kris Kowdley, Marcelo Kugelmas, Jay Lalezari, Eric Lawitz, Claudia Martorell, Anthony Mills, Giuseppe Morelli, Ronald Nahass, Anders Nyberg, Ponni Perumalswami, Gary Poleynard, K Rajender Reddy, Maribel Roderiguez-Torres, Peter Ruane, Vinod Rustgi, Michael Ryan, Michael Saag, Eugene Schiff, Thomas Sepe, Aasim Sheikh, Mitchell Shiffman, Coleman Smith, Mark Sulkowski, David Wyles, Ziad Younes, Zobair Younossi
Abstract
Background: Patients chronically infected with hepatitis C virus (HCV) genotype 2 or 3 for whom treatment with peginterferon is not an option, or who have not had a response to prior interferon treatment, currently have no approved treatment options. In phase 2 trials, regimens including the oral nucleotide polymerase inhibitor sofosbuvir have shown efficacy in patients with HCV genotype 2 or 3 infection.
Methods: We conducted two randomized, phase 3 studies involving patients with chronic HCV genotype 2 or 3 infection. In one trial, patients for whom treatment with peginterferon was not an option received oral sofosbuvir and ribavirin (207 patients) or matching placebo (71) for 12 weeks. In a second trial, patients who had not had a response to prior interferon therapy received sofosbuvir and ribavirin for 12 weeks (103 patients) or 16 weeks (98). The primary end point was a sustained virologic response at 12 weeks after therapy.
Results: Among patients for whom treatment with peginterferon was not an option, the rate of a sustained virologic response was 78% (95% confidence interval [CI], 72 to 83) with sofosbuvir and ribavirin, as compared with 0% with placebo (P<0.001). Among previously treated patients, the rate of response was 50% with 12 weeks of treatment, as compared with 73% with 16 weeks of treatment (difference, -23 percentage points; 95% CI, -35 to -11; P<0.001). In both studies, response rates were lower among patients with genotype 3 infection than among those with genotype 2 infection and, among patients with genotype 3 infection, lower among those with cirrhosis than among those without cirrhosis. The most common adverse events were headache, fatigue, nausea, and insomnia; the overall rate of discontinuation of sofosbuvir was low (1 to 2%).
Conclusions: In patients with HCV genotype 2 or 3 infection for whom treatment with peginterferon and ribavirin was not an option, 12 or 16 weeks of treatment with sofosbuvir and ribavirin was effective. Efficacy was increased among patients with HCV genotype 2 infection and those without cirrhosis. In previously treated patients with genotype 3 infection, 16 weeks of therapy was significantly more effective than 12 weeks. (Funded by Gilead Sciences; POSITRON and FUSION ClinicalTrials.gov numbers, NCT01542788 and NCT01604850, respectively.).
Source: PubMed