Triple Regimen of Direct-acting Antivirals Achieves High Sustained Virologic Response Rates in Patients with Hepatitis C

Results from a phase III clinical trial show an interferon-free treatment regimen of three direct-acting antiviral produced sustained virologic response rates at 12 weeks (SVR12) of 96% without ribavirin (and nearly 100% when ribavirin was included in the regimen) in hepatitis C genotype 1b patients.

These results have broad implications for the management of hepatitis C, as genotype 1 is the most prevalent hepatitis C virus (HCV) subgroup in the world.

Pietro Andreone, MD, of the University of Bologna in Italy, presented results from the PEARL-II study Tuesday at Digestive Disease Week 2014 in Chicago, IL. The global, multicenter, randomized, open-label, controlled study evaluated the efficacy and safety of 12 weeks of treatment with combination ABT 450/ritonavir/ombitasvir (formerly known as ABT-267) and dasabuvir (formerly known as ABT-333) with and without ribavirin in non-cirrhotic, treatment-experienced adult patients. The approach has now been tested in more than 2,000 patients.

Patients in PEARL-II were randomized to receive a fixed-dose combination of the protease inhibitor ABT-450 150 mg dosed with ritonavir 100 mg QD, coformulated with the NS5A inhibitor ombitasvir 25 mg QD, and the non-nucleoside polymerase inhibitor dasabuvir 250 mg BID (known as the “3D regimen”), with ribavirin (Arm A) or without ribavirin (Arm B) for 12 weeks. The combination of three different mechanisms of action interrupts the HCV replication process with the goal of optimizing SVR rates across different patient populations.

The study population consisted of 179 patients recruited in Europe and the US. Ninety-one patients were randomized to receive the combination regimen without ribavirin for 12 weeks, and 88 patients were randomized to receive the regimen with ribavirin for 12 weeks. In the ribavirin-free arm, 97 percent of patients achieved SVR12_, while 100 percent of patients treated with ribavirin achieved SVR12.

Patients were predominantly male and Caucasian, with a mean age near 50.

The most commonly reported adverse events were fatigue and headache. None of the patients in the ribavirin-free arm and 2% of those in the ribavirin arm discontinued treatment. No patients in either arm of the study experienced virologic relapse or breakthrough.

The three-drug regimen without ribavirin was associated with lower rates of laboratory abnormalities, including bilirubin elevation and hemoglobin decrease.

Twelve weeks after treatment, researchers compared SVR rates for each group to a historical telaprevir plus pegylated interferon and RBV threshold.

Adverse events were recorded for all patients receiving at least one dose of the study drug. Adverse events were generally mild and easy to manage, Andreone said. The most frequent adverse events were fatigue (31.9% vs. 15.8%, P = .015), headache (24.2% vs. 23.2%, P > .05), and nausea (20.9% vs 6.3%, P = .005) in Arms A and B, respectively. Two patients in Arm A discontinued treatment due to adverse events.

Andreone said that this drug combination with or without ribavirin achieves optimal efficacy regardless of the type of prior response to treatment.