Published: Nov 8, 2013 | Updated: Nov 8, 2013
Coverage of Hepatitis C Virus is supported in part by an independent educational grant from AbbVie Pharmaceuticals.
By Ed Susman , Contributing Writer, MedPage Today
Reviewed by F. Perry Wilson, MD, MSCE; Instructor of Medicine, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner
- Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
- Note that in this uncontrolled trial of patients with HCV, the combination of daclatasvir plus asunaprevir was very effective in inducing virologic response rates.
- Be aware that the trial only enrolled patients who had failed or were ineligible for interferon therapy.
WASHINGTON -- Patients who failed to respond to standard treatment for hepatitis C virus (HCV) infection achieved greater than 80% sustained virologic response at 24 weeks with an all-oral regimen that eschewed both interferon and ribavirin, researchers reported here.
Among 135 patients who were either ineligible for interferon therapy or who were intolerant of the treatment, 87.4% achieved a sustained virologic response -- basically a treatment cure, reported Kazuaki Chayama, MD, PhD, professor of medicine and director of Hiroshima University Hospital.
In his plenary session report at the annual meeting of the American Association for the Study of Liver Diseases, Chayama also reported that 80.5% of 87 previous non-responders or partial responders achieved a sustained virologic response at 24 weeks.
He said that the response at 12 weeks was virtually the same as at 24 weeks: 88.1% of those ineligible or intolerant of interferon-based therapy reached the milestone compared with 80.5% of the non-responders or partial responders achieving a sustained virologic response at 12 weeks.
"Overall, 84.7% of these patients with limited therapeutic options and those patients typically associated with poor responses to other therapies were able to achieve a sustained virologic response," he said.
The 135 patients in the study received daclatasvir 60 mg once daily plus asunaprevir 100 mg twice daily. The researchers also enrolled 87 non-responders to previous therapy who received the same treatment regimen.
"Current treatment for chronic hepatitis C virus infection consists of pegylated interferon/ribavirin combined with a direct-acting antiviral," he explained. "In Japan, many patients are excluded from therapy due to the combined effect of an aging Japanese population with chronic hepatitis C virus and the poor tolerability profile with peginterferon/ribavirin-based therapy in this population."
He noted that although telaprevir/peginterferon/ribavirin therapy was approved for both treatment-naïve and treatment-experienced patients, the efficacy in nonresponder patients with hepatitis C virus genotype-1 was insufficient -- about one-third of patients responded.
The two investigative agents attack the virus in different ways. Daclatasvir is a potent NS5A replication complex inhibitor with pan-genotypic antiviral activity. Asunaprevir is a potent NS3 protease inhibitor with antiviral activity against genotypes 1, 4, 5, and 6. Chayama said the phase III study he described follows successful phase II studies showing a strong impact on patients with genotype 1b.
The median age of the 222 participants in the trial was 62.5, about 35% were men, and about 10% were diagnosed with cirrhosis. Baseline factors, including male gender, advanced age, high baseline hepatitis C virus RNA, and cirrhosis, did not appear to have an impact on response rates, Chayama said.
Overall 12.6% of the patients in the study discontinued therapy -- 6.8% due to lack of efficacy and 5% due to adverse events. Chayama said 5.6% of patients experienced serious adverse events. There were no deaths in the study.
Although the study was conducted among a Japanese population, Michael Fried, MD, professor of medicine and director of the University of North Carolina Liver Center in Chapel Hill, told MedPage Today, "These results can be extrapolated to an American or European hepatitis C virus population that had genotype 1 infection."
"It will work in this population but it will be tested in this population as well. These drugs will have to be more broadly studied. As you have seen if we get the right combination of drugs we can get successful results," Fried said.
The Japanese population mainly had genotype 1b infections, he said. Yet the success rate in achieving sustained virologic response was greater than 80%. "When I first started treating hepatitis C virus infection in the 1990s we were getting sustained virologic response rate in the 7% area, and to be getting response in the 80% to 90% levels we are seeing today is phenomenal."
He acknowledged that historically genotype 1 hepatitis C infection has been considered a more difficult disease to treat than genotypes 2 or 3, but in studies presented at The Liver Meeting 2013, "What has emerged is that genotype 3 is the new genotype 1. With these new drugs I think there has been a surprise that we get suboptimal results with genotype 3."
Primary source: American Association for the Study of Liver Diseases
Source reference: Chayama M, et al "All-oral combination of daclatasvir plus asunaprevir in interferon ineligible naive/intolerant and nonresponder Japanese patients chronically infected with HCV genotype 1b: Results from a phase 3 trial" AASLD 2013.