A phase 2 study of filibuvir in combination with pegylated IFN alfa and ribavirin for chronic HCV
Objectives. Filibuvir is a non-nucleoside inhibitor of hepatitis C virus (HCV) polymerase. This study evaluated the safety and efficacy of filibuvir plus pegylated interferon alfa-2a (pegIFN)/ribavirin.Material and methods. Treatment-naïve, HCV genotype-1 patients were randomized to receive filibuvi...
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doaj-6f954e6b89a54326b802d03c0f1bee312021-06-09T05:52:19ZengElsevierAnnals of Hepatology1665-26812014-07-01134364375A phase 2 study of filibuvir in combination with pegylated IFN alfa and ribavirin for chronic HCVMaribel Rodriguez-Torres0Eric M. Yoshida1Patrick Marcellin2Subasree Srinivasan3Vivek S. Purohit4Cunshan Wang5Jennifer L. Hammond, Ph.D.6Fundación de Investigación and San Juan Bautista School of Medicine, San Juan, Puerto Rico, USAUniversity of British Columbia and Vancouver General Hospital, Vancouver, B.C. CanadaService d’Hépatologie, Hôpital Beaujon, Université Paris-Diderot, Clichy, FrancePfizer, Global Innovative Pharma Business Unit, Groton, CT, and Collegeville, PA, USAPfizer, Global Innovative Pharma Business Unit, Groton, CT, and Collegeville, PA, USAPfizer, Global Innovative Pharma Business Unit, Groton, CT, and Collegeville, PA, USAPfizer, Global Innovative Pharma Business Unit, Groton, CT, and Collegeville, PA, USA; Correspondence and reprint request:Objectives. Filibuvir is a non-nucleoside inhibitor of hepatitis C virus (HCV) polymerase. This study evaluated the safety and efficacy of filibuvir plus pegylated interferon alfa-2a (pegIFN)/ribavirin.Material and methods. Treatment-naïve, HCV genotype-1 patients were randomized to receive filibuvir 300 or 600 mg twice daily (BID) or placebo plus pegIFN (180 Mg/wk) and ribavirin (1,000/1,200 mg BID) for 24 weeks. Filibuvir patients who achieved defined response through week 24 discontinued therapy at week 24. All other patients continued on open-label peglFN/ribavirin through week 48. The primary endpoint was the proportion of patients who achieved sustained virologic response (SVR) defined as HCV RNA < 15 IU/mL at end of treatment (weeks 24 or 48) and week 72.Results. Overall, 288 patients were randomized and treated. SVR was achieved by 41.7, 39.6, and 45.8% of patients in the filibuvir 300 mg, 600 mg, and placebo arms, respectively. While the addition of filibuvir to pegIFN/ribavirin improved on-treatment virologic response parameters, this did not translate into improved SVR rates due to a high rate of virologic relapse following completion of therapy (300 mg: 35.9%; 600 mg: 42.9%; placebo: 25.4%). The most commonly reported adverse events were nausea, fatigue, headache, and insomnia, and were reported at similar rates across arms. Conclusions. Filibuvir plus pegIFN/ribavirin did not improve the percentage of patients achieving SVR compared with administration of pegIFN/ribavirin alone. However, the agent was well tolerated and was associated with higher on-treatment virologic response parameters. Further evaluation of filibuvir in combination with other direct-acting antiviral agents may be considered.http://www.sciencedirect.com/science/article/pii/S1665268119308439NS5BNon-nucleoside inhibitorTreatment naïveSafetyEfficacy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Maribel Rodriguez-Torres Eric M. Yoshida Patrick Marcellin Subasree Srinivasan Vivek S. Purohit Cunshan Wang Jennifer L. Hammond, Ph.D. |
spellingShingle |
Maribel Rodriguez-Torres Eric M. Yoshida Patrick Marcellin Subasree Srinivasan Vivek S. Purohit Cunshan Wang Jennifer L. Hammond, Ph.D. A phase 2 study of filibuvir in combination with pegylated IFN alfa and ribavirin for chronic HCV Annals of Hepatology NS5B Non-nucleoside inhibitor Treatment naïve Safety Efficacy |
author_facet |
Maribel Rodriguez-Torres Eric M. Yoshida Patrick Marcellin Subasree Srinivasan Vivek S. Purohit Cunshan Wang Jennifer L. Hammond, Ph.D. |
author_sort |
Maribel Rodriguez-Torres |
title |
A phase 2 study of filibuvir in combination with pegylated IFN alfa and ribavirin for chronic HCV |
title_short |
A phase 2 study of filibuvir in combination with pegylated IFN alfa and ribavirin for chronic HCV |
title_full |
A phase 2 study of filibuvir in combination with pegylated IFN alfa and ribavirin for chronic HCV |
title_fullStr |
A phase 2 study of filibuvir in combination with pegylated IFN alfa and ribavirin for chronic HCV |
title_full_unstemmed |
A phase 2 study of filibuvir in combination with pegylated IFN alfa and ribavirin for chronic HCV |
title_sort |
phase 2 study of filibuvir in combination with pegylated ifn alfa and ribavirin for chronic hcv |
publisher |
Elsevier |
series |
Annals of Hepatology |
issn |
1665-2681 |
publishDate |
2014-07-01 |
description |
Objectives. Filibuvir is a non-nucleoside inhibitor of hepatitis C virus (HCV) polymerase. This study evaluated the safety and efficacy of filibuvir plus pegylated interferon alfa-2a (pegIFN)/ribavirin.Material and methods. Treatment-naïve, HCV genotype-1 patients were randomized to receive filibuvir 300 or 600 mg twice daily (BID) or placebo plus pegIFN (180 Mg/wk) and ribavirin (1,000/1,200 mg BID) for 24 weeks. Filibuvir patients who achieved defined response through week 24 discontinued therapy at week 24. All other patients continued on open-label peglFN/ribavirin through week 48. The primary endpoint was the proportion of patients who achieved sustained virologic response (SVR) defined as HCV RNA < 15 IU/mL at end of treatment (weeks 24 or 48) and week 72.Results. Overall, 288 patients were randomized and treated. SVR was achieved by 41.7, 39.6, and 45.8% of patients in the filibuvir 300 mg, 600 mg, and placebo arms, respectively. While the addition of filibuvir to pegIFN/ribavirin improved on-treatment virologic response parameters, this did not translate into improved SVR rates due to a high rate of virologic relapse following completion of therapy (300 mg: 35.9%; 600 mg: 42.9%; placebo: 25.4%). The most commonly reported adverse events were nausea, fatigue, headache, and insomnia, and were reported at similar rates across arms. Conclusions. Filibuvir plus pegIFN/ribavirin did not improve the percentage of patients achieving SVR compared with administration of pegIFN/ribavirin alone. However, the agent was well tolerated and was associated with higher on-treatment virologic response parameters. Further evaluation of filibuvir in combination with other direct-acting antiviral agents may be considered. |
topic |
NS5B Non-nucleoside inhibitor Treatment naïve Safety Efficacy |
url |
http://www.sciencedirect.com/science/article/pii/S1665268119308439 |
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