ABT-450/r–Ombitasvir and Dasabuvir with or without Ribavirin for HCV

Peter Ferenci, M.D., David Bernstein, M.D., Jacob Lalezari, M.D., Daniel Cohen, M.D., Yan Luo, M.D., Ph.D., Curtis Cooper, M.D., Edward Tam, M.D., Rui T. Marinho, M.D., Ph.D., Naoky Tsai, M.D., Anders Nyberg, M.D., Terry D. Box, M.D., Ziad Younes, M.D., Pedram Enayati, M.D., Sinikka Green, M.D., Yaacov Baruch, M.D., Bal Raj Bhandari, M.D., Florin Alexandru Caruntu, M.D., Ph.D., Thomas Sepe, M.D., Vladimir Chulanov, M.D., Ph.D., Ewa Janczewska, M.D., Ph.D., Giuliano Rizzardini, M.D., Judit Gervain, M.D., Ph.D., Ramon Planas, M.D., Christophe Moreno, M.D., Ph.D., Tarek Hassanein, M.D., Wangang Xie, Ph.D., Martin King, Ph.D., Thomas Podsadecki, M.D., and K. Rajender Reddy, M.D.

May 4, 2014DOI: 10.1056/NEJMoa1402338

Abstract
Article
References: BACKGROUND
The interferon-free regimen of ABT-450 with ritonavir (ABT-450/r), ombitasvir, and dasabuvir with or without ribavirin has shown efficacy in inducing a sustained virologic response in a phase 2 study involving patients with hepatitis C virus (HCV) genotype 1 infection. We conducted two phase 3 trials to examine the efficacy and safety of this regimen in previously untreated patients with HCV genotype 1 infection and no cirrhosis.
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METHODS
We randomly assigned 419 patients with HCV genotype 1b infection (PEARL-III study) and 305 patients with genotype 1a infection (PEARL-IV study) to 12 weeks of ABT-450/r–ombitasvir (at a once-daily dose of 150 mg of ABT-450, 100 mg of ritonavir, and 25 mg of ombitasvir), dasabuvir (250 mg twice daily), and ribavirin administered according to body weight or to matching placebo for ribavirin. The primary efficacy end point was a sustained virologic response (an HCV RNA level of <25 IU per milliliter) 12 weeks after the end of treatment.
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RESULTS
The study regimen resulted in high rates of sustained virologic response among patients with HCV genotype 1b infection (99.5% with ribavirin and 99.0% without ribavirin) and among those with genotype 1a infection (97.0% and 90.2%, respectively). Of patients with genotype 1b infection, 1 had virologic failure, and 2 did not have data available at post-treatment week 12. Among patients with genotype 1a infection, the rate of virologic failure was higher in the ribavirin-free group than in the ribavirin group (7.8% vs. 2.0%). In both studies, decreases in the hemoglobin level were significantly more common in patients receiving ribavirin. Two patients (0.3%) discontinued the study drugs owing to adverse events. The most common adverse events were fatigue, headache, and nausea.
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CONCLUSIONS
Twelve weeks of treatment with ABT-450/r–ombitasvir and dasabuvir without ribavirin was associated with high rates of sustained virologic response among previously untreated patients with HCV genotype 1 infection. Rates of virologic failure were higher without ribavirin than with ribavirin among patients with genotype 1a infection but not among those with genotype 1b infection. (Funded by AbbVie; PEARL-III and PEARL-IV ClinicalTrials.gov numbers, NCT01767116 andNCT01833533.)
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