TY - JOUR
T1 - Efficacy of an interferon- and ribavirin-free regimen of daclatasvir, asunaprevir, and BMS-791325 in treatment-naive patients with HCV genotype 1 infection
AU - Everson, Gregory T.
AU - Sims, Karen D.
AU - Rodriguez-Torres, Maribel
AU - Hézode, Christophe
AU - Lawitz, Eric
AU - Bourlière, Marc
AU - Loustaud-Ratti, Veronique
AU - Rustgi, Vinod
AU - Schwartz, Howard
AU - Tatum, Harvey
AU - Marcellin, Patrick
AU - Pol, Stanislas
AU - Thuluvath, Paul J.
AU - Eley, Timothy
AU - Wang, Xiaodong
AU - Huang, Shu Pang
AU - McPhee, Fiona
AU - Wind-Rotolo, Megan
AU - Chung, Ellen
AU - Pasquinelli, Claudio
AU - Grasela, Dennis M.
AU - Gardiner, David F.
N1 - Funding Information:
Funding This study was sponsored by Bristol-Myers Squibb . The study was designed and conducted by the sponsor in collaboration with the principal investigators. The sponsor collected the data, monitored the study conduct, and performed the statistical analyses.
PY - 2014/2
Y1 - 2014/2
N2 - Background & Aims The combination of peginterferon and ribavirin with telaprevir or boceprevir is the standard treatment of hepatitis C virus (HCV) genotype 1 infection. However, these drugs are not well tolerated because of their side effects and suboptimal virologic responses. In a phase 2a, open-label study, we examined the safety and efficacy of an interferon-free, ribavirin-free regimen of direct-acting antivirals, comprising daclatasvir (an NS5A replication complex inhibitor), asunaprevir (an NS3 protease inhibitor), and BMS-791325 (a non-nucleoside NS5B inhibitor), in patients with chronic HCV infection. Methods We analyzed data from 66 treatment-naive patients with HCV genotype 1 infection without cirrhosis who were assigned randomly to groups given daclatasvir (60 mg, once daily), asunaprevir (200 mg, twice daily), and BMS-791325 (75 or 150 mg, twice daily) for 12 or 24 weeks. The primary end point was an HCV-RNA level less than 25 IU/mL at 12 weeks after treatment (sustained virologic response at 12 weeks [SVR12]). Results In 64 patients, HCV-RNA levels were less than 25 IU/mL by week 4 of treatment (including 48 of 49 patients with HCV genotype 1a infection and 45 of 46 patients with the non-CC interleukin 28B genotype). Sixty-one patients (92%) achieved SVR12, based on a modified intention-to-treat analysis. Virologic responses were similar between 12 and 24 weeks of treatment. During the study, 2 patients experienced viral breakthrough and 1 patient relapsed. There were no grade 3-4 increases in levels of alanine or aspartate aminotransferases or bilirubin; there were no deaths or discontinuations resulting from serious adverse events or adverse events related to the treatment regimen. The most common adverse events were headache, asthenia, and gastrointestinal symptoms. Conclusions In a phase 2a study, the all-oral, interferon-free, and ribavirin-free regimen of daclatasvir, asunaprevir, and BMS-791325 was well tolerated and achieved high rates of SVR12 in patients with HCV genotype 1 infection. Further studies of this regimen are warranted. ClinicalTrials.gov, number NCT01455090.
AB - Background & Aims The combination of peginterferon and ribavirin with telaprevir or boceprevir is the standard treatment of hepatitis C virus (HCV) genotype 1 infection. However, these drugs are not well tolerated because of their side effects and suboptimal virologic responses. In a phase 2a, open-label study, we examined the safety and efficacy of an interferon-free, ribavirin-free regimen of direct-acting antivirals, comprising daclatasvir (an NS5A replication complex inhibitor), asunaprevir (an NS3 protease inhibitor), and BMS-791325 (a non-nucleoside NS5B inhibitor), in patients with chronic HCV infection. Methods We analyzed data from 66 treatment-naive patients with HCV genotype 1 infection without cirrhosis who were assigned randomly to groups given daclatasvir (60 mg, once daily), asunaprevir (200 mg, twice daily), and BMS-791325 (75 or 150 mg, twice daily) for 12 or 24 weeks. The primary end point was an HCV-RNA level less than 25 IU/mL at 12 weeks after treatment (sustained virologic response at 12 weeks [SVR12]). Results In 64 patients, HCV-RNA levels were less than 25 IU/mL by week 4 of treatment (including 48 of 49 patients with HCV genotype 1a infection and 45 of 46 patients with the non-CC interleukin 28B genotype). Sixty-one patients (92%) achieved SVR12, based on a modified intention-to-treat analysis. Virologic responses were similar between 12 and 24 weeks of treatment. During the study, 2 patients experienced viral breakthrough and 1 patient relapsed. There were no grade 3-4 increases in levels of alanine or aspartate aminotransferases or bilirubin; there were no deaths or discontinuations resulting from serious adverse events or adverse events related to the treatment regimen. The most common adverse events were headache, asthenia, and gastrointestinal symptoms. Conclusions In a phase 2a study, the all-oral, interferon-free, and ribavirin-free regimen of daclatasvir, asunaprevir, and BMS-791325 was well tolerated and achieved high rates of SVR12 in patients with HCV genotype 1 infection. Further studies of this regimen are warranted. ClinicalTrials.gov, number NCT01455090.
KW - DAA
KW - Drug Combination
KW - Liver Disease
KW - Therapy
UR - http://www.scopus.com/inward/record.url?scp=84892761609&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84892761609&partnerID=8YFLogxK
U2 - 10.1053/j.gastro.2013.10.057
DO - 10.1053/j.gastro.2013.10.057
M3 - Article
C2 - 24184132
AN - SCOPUS:84892761609
SN - 0016-5085
VL - 146
SP - 420
EP - 429
JO - Gastroenterology
JF - Gastroenterology
IS - 2
ER -