June 1, 2013

ABT-450 combined with ritonavir, in addition to ABT-333 and ribavirin: A race for an interferon-free regimen to cure HCV infection

Journal of Hepatology

Article in Press

Tarik Asselah

Received 11 March 2013; received in revised form 15 May 2013; accepted 15 May 2013. published online 28 May 2013.
Accepted Manuscript



There is a need for interferon-free treatment regimens for hepatitis C virus (HCV) infection. The goal of this study was to evaluate ABT-450, a potent HCV NS3 protease inhibitor, combined with low-dose ritonavir (ABT-450/r), in addition to ABT-333, a nonnucleoside NS5B polymerase inhibitor, and ribavirin, for the treatment of HCV infection.


We conducted a 12-week, phase 2a, open-label study involving patients who had HCV genotype 1 infection without cirrhosis. All patients received ABT-333 (400 mg twice daily) and ribavirin (1000 to 1200 mg per day) and one of two daily doses of ABT-450/r. Groups 1 and 2 included previously untreated patients; group 1 received 250 mg of ABT-450 and 100 mg of ritonavir, and group 2 received 150 mg and 100 mg, respectively. Group 3, which included patients who had had a null or partial response to previous therapy with peginterferon and ribavirin, received daily doses of 150 mg of ABT-450 and 100 mg of ritonavir. The primary end point was an undetectable level of HCV RNA from week 4 through week 12 (extended rapid virologic response)


A total of 17 of the 19 patients in group 1 (89%) and 11 of the 14 in group 2 (79%) had an extended rapid virologic response; a sustained virologic response 12 weeks after the end of treatment was achieved in 95% and 93% of the patients, respectively. In group 3, 10 of 17 patients (59%) had an extended rapid virologic response, and 8 (47%) had a sustained virologic response 12 weeks after therapy; 6 patients had virologic breakthrough, and 3 had a relapse. Adverse events included abnormalities in liver-function tests, fatigue, nausea, headache, dizziness, insomnia, pruritus, rash, and vomiting


This preliminary study suggests that 12 weeks of therapy with a combination of a protease inhibitor, a non-nucleoside polymerase inhibitor, and ribavirin may be effective for treatment of HCV genotype 1 infection. (Funded by Abbott; ClinicalTrials.gov number, NCT01306617.).

Abbreviations: DAA, direct-acting antivirals, PegIFN, pegylated interferon, SVR, sustained virological response, eRVR, extended rapid virological response, RVR, rapid virologic response

Keywords: Direct-acting antivirals, Sustained virological response, Chronic hepatitis C, NS5A inhibitors, Safety, Resistance

No full text is available. To read the body of this article, please view the PDF online.

PII: S0168-8278(13)00351-6


© 2013 Published by Elsevier Inc.


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