Two interferon-free combination therapies yielded sustained virologic responses of 96%-100% in an international, open-label, phase III, randomized trial involving 186 patients with refractory hepatitis C virus type 1b infection, Dr. Pietro Andreone and his colleagues reported in the August 2014 issue of Gastroenterology (doi:org/10.1053/j.gastro.2014.04.037).
Twelve weeks of treatment using the combination regimen plus ribavirin (91 patients) or the same regimen without ribavirin (95 patients) produced sustained virologic responses (SVRs) that were noninferior to historic SVRs reported in the literature for comparable patients treated with telaprevir plus pegylated-interferon plus ribavirin.
Source: American Gastroenterological Institute
None of the patients taking the new combination regimen experienced virologic failure while taking the drugs or relapse during the year after completing treatment. And adverse effects were characterized as "generally mild and manageable," said Dr. Andreone of the department of medical science and surgery, University of Bologna (Italy), and his associates.
HCV type 1b is the most prevalent genotype worldwide. Patients with this genotype who have failed on standard treatments "have not been extensively studied with currently approved or investigational interferon-free regimens, hence this large patient population represents a group with unmet need," the investigators noted.
They assessed such patients at 43 medical centers in Austria, Belgium, Italy, the Netherlands, Portugal, Puerto Rico, Sweden, Switzerland, Turkey, and the United States. All were aged between 18 and 70 years, and all were free of cirrhosis and coinfections.
The daily oral combination regimen consisted of ABT-450, a protease inhibitor that has shown in-vitro antiviral activity; ritonavir, a CYP3A4 inhibitor that enables once-daily rather than more frequent dosing of the ABT-450; ombitasvir, an HCV NS5A inhibitor; and dasabuvir, an HCV NS5B RNA nonnucleoside polymerase inhibitor.
The primary efficacy endpoint was an SVR rate noninferior to the historical rate for interferon-containing regimens in comparable patients. In the intention-to-treat analysis, the SVRs met and surpassed that standard, at 96.6% for ABT-450/ritonavir/ombitasvir/dasabuvir plus ribavirin and 100% for ABT-450/ritonavir/ombitasvir/dasabuvir without ribavirin.
Moreover, of the three patients who did not achieve a sustained virologic response, two had discontinued the study drug because of adverse events and one was lost to follow-up after only 4 weeks of treatment.
The most common adverse events were fatigue, headache, and nausea, all of which were significantly more frequent among patients taking ribavirin. Insomnia, anemia, rash, and elevated bilirubin also were related to ribavirin and were easily managed.
Only two patients discontinued treatment due to adverse events, neither of which were considered to be related to a study drug. One patient developed pancreatitis and another developed anxiety, tachycardia, and dyspnea.
Three other serious adverse events – cellulitis, nephrolithiasis, and osteoarthritis – also were judged to be unrelated to the study treatments.
Declines in hemoglobin levels occurred in 42% of the patients who received ribavirin but only 5.5% of those who did not. However, clinically significant declines occurred in only two patients, and neither of them required transfusions or erythropoietin.
Their findings show that 12 weeks of combined oral ABT-450/ritonavir/ombitasvir/dasabuvir therapy without ribavirin is at least as effective as interferon-containing regimens, and it produces significantly fewer and less severe adverse effects, the investigators said.
This study was somewhat limited in that it used an open-label design and did not include patients with concomitant cirrhosis, hepatitis B viral infection, or HIV infection, they added.
This study was sponsored by AbbVie, which also participated in the study design, data collection and analysis, and manuscript preparation. Dr. Andreone reported receiving research support from, being a consultant for, or serving on advisory committees for Roche, Merck, Gilead Sciences, Janssen Cilag, AbbVie, Boehringer Ingelheim, and BMS; his associates reported ties to numerous industry sources.