The interferon-free regimen of ABT-450, ritonavir, ombitasvir, and dasabuvir, with or without ribavirin, produces a high rate of SVR12 in treatment-experienced patients with HCV genotype 1b infection. Both regimens are well tolerated, as shown by the low rate of discontinuations and generally mild adverse events. ClinicalTrials.gov number: NCT01674725.

GIFT‐I is a phase 3 trial evaluating the efficacy and safety of a 12‐week regimen of coformulated ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (r) for treatment of Japanese hepatitis C virus genotype 1b–infected patients. It consists of a double‐blind, placebo‐controlled substudy of patients without cirrhosis and an open‐label substudy of patients with compensated cirrhosis. Patients without cirrhosis were randomized 2:1 to once‐daily OBV/PTV/r (25 mg/150 mg/100 mg; group A) or placebo (group B). Patients with cirrhosis received open‐label OBV/PTV/r (group C). The primary efficacy endpoint was the rate of sustained virological response 12 weeks posttreatment in interferon‐eligible, treatment‐naive patients without cirrhosis and hepatitis C virus RNA ≥100,000 IU/mL in group A. A total of 321 patients without cirrhosis were randomized and dosed with double‐blind study drug (106 received double‐blind placebo and later received open‐label OBV/PTV/r), and 42 patients with cirrhosis were enrolled and dosed with open‐label OBV/PTV/r. In the primary efficacy population, the rate of sustained virological response 12 weeks posttreatment was 94.6% (106/112, 95% confidence interval 90.5‐98.8). Sustained virological response 12 weeks posttreatment rates were 94.9% (204/215) in group A, 98.1% (104/106) in group B (open‐label), and 90.5% (38/42) in group C. Overall, virological failure occurred in 3.0% (11/363) of patients who received OBV/PTV/r. The rate of discontinuation due to adverse events was 0%‐2.4% in the three patient groups receiving OBV/PTV/r. The most frequent adverse event in patients in any group was nasopharyngitis. Conclusion: In this broad hepatitis C virus genotype 1b–infected Japanese patient population with or without cirrhosis, treatment with OBV/PTV/r for 12 weeks was highly effective and demonstrated a favorable safety profile. (Hepatology 2015;62:1037‐1046)

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Approximately 2 million Japanese individuals are infected with hepatitis C virus and are at risk for cirrhosis, end‐stage liver disease, and hepatocellular carcinoma. Patients in whom interferon (IFN)/ribavirin (RBV) therapy has failed remain at risk as effective therapeutic options are limited. This phase 2, randomized, open‐label study evaluated an IFN‐ and RBV‐free regimen of once‐daily ombitasvir (ABT‐267), an NS5A inhibitor, plus paritaprevir (ABT‐450), an NS3/4A protease inhibitor dosed with ritonavir (paritaprevir/ritonavir), in pegylated IFN/RBV treatment–experienced Japanese patients with hepatitis C virus subtype 1b or genotype 2 infection. Patients without cirrhosis (aged 18‐75 years) with subtype 1b infection received ombitasvir 25 mg plus paritaprevir/ritonavir 100/100 mg or 150/100 mg for 12 or 24 weeks; patients with genotype 2 infection received ombitasvir 25 mg plus paritaprevir/ritonavir 100/100 mg or 150/100 mg for 12 weeks. Sustained virologic response (SVR) at posttreatment week 24 (SVR24) was the primary endpoint. Adverse events were collected throughout the study. One hundred ten patients received ≥1 dose of study medication. In the subtype 1b cohort, SVR24 rates were high (88.9%‐100%) regardless of paritaprevir dose or treatment duration. In the genotype 2 cohort, SVR24 rates were 57.9% and 72.2% with 100 mg and 150 mg of paritaprevir, respectively. The SVR24 rate was higher in patients with subtype 2a (90%) than 2b (27%). Concordance between SVR12 and SVR24 was 100%. The most common adverse events overall were nasopharyngitis (29%) and headache (14%). Conclusion: In this difficult‐to‐treat population of patients in whom prior pegylated IFN/RBV had failed, ombitasvir/paritaprevir/ritonavir demonstrated potent antiviral activity with a favorable safety profile among Japanese patients with hepatitis C virus genotype 1b or 2a infection. (Hepatology 2015;61:1523–1532)

Curative treatment of patients who previously failed hepatitis C virus (HCV) therapies is critical to achieving HCV elimination. Glecaprevir/pibrentasvir (G/P) demonstrated high rates of sustained virologic response at post-treatment week 12 (SVR12) in patients with HCV infection; however, retreatment of patients who failed G/P has yet to be evaluated. MAGELLAN-3 is an ongoing, open-label, phase IIIb trial evaluating the efficacy and safety of G/P plus sofosbuvir (SOF) plus ribavirin (RBV) as a retreatment regimen for patients who had virologic failure with G/P in an AbbVie study. Patients with HCV genotype (GT) 1, 2, 4, 5 or 6 infection, without cirrhosis, and naïve to NS3/4A protease and NS5A inhibitors prior to virologic failure with G/P received 12 weeks of treatment; patients with GT3, and/or compensated cirrhosis, and/or experience with NS3/4A protease and NS5A inhibitors prior to virologic failure with G/P received 16 weeks of treatment. The primary efficacy endpoint was the SVR12 rate. Safety, tolerability, and presence of resistance-associated substitutions (RASs) were assessed. To date, 23 patients enrolled: 30% (7/23), 9% (2/23), and 61% (14/23) of patients had GT1, 2, and 3 infections, respectively; 30% (7/23) of patients had compensated cirrhosis, and 91% (21/23) had baseline RASs in NS5A. The SVR12 rate was 96% (22/23); 1 patient with GT1a infection and compensated cirrhosis had virologic failure. One unrelated serious adverse event (AE) of symptomatic cholelithiasis occurred. There were no treatment discontinuations. Retreatment of G/P virologic failures with G/P plus SOF plus RBV for 12 or 16 weeks was well-tolerated and highly efficacious, regardless of HCV genotype or baseline RASs.