EASL-Oral HCV Combo Effective for Genotype One

Oral HCV Combo Effective for Genotype One

By Michael Smith, North American Correspondent, MedPage Today
Published: April 20, 2012

Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania.

An all-oral treatment regimen for hepatitis C had high response rates among patients with a hard-to-treat type of virus, a researcher reported.

After 12 weeks of therapy with two investigational direct-acting agents and ribavirin, 91% of patients with genotype one virus went on to have a sustained virologic response (SVR) 24 weeks later, according to Eric Lawitz, MD, of Alamo Medical Research in San Antonio.

It's the first time such a regimen -- given without interferon-alfa -- has shown such high response rates among patients with that type of HCV, Lawitz said at the meeting of the European Association for the Study of the Liver in Barcelona.

Action Points
•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.
•In this small study, a combination oral therapeutic regimen, without interferon-alfa, including a investigational protease inhibitor and an investigational polymerase inhibitor was well tolerated and very effective in treatment of naive noncirrhotic patients with genotype 1 HCV.

The regimen included one standard drug, ribavirin, as well as ABT-450/r, which is given with ritonavir (Norvir) and inhibits the viral NS3 protease inhibitor, and ABT-072, a non-nucleoside NS5B polymerase inhibitor.

In a small study of 11 patients who had not previously been treated for the virus, all showed sharp declines in hepatitis C RNA within three weeks of starting the 12 weeks of therapy and all had undetectable virus from week five through the end of treatment.

One patient relapsed by week eight after the end of treatment, but 91% were still virus-free at week 24 post-therapy and 82% were still clear by 36 weeks, Lawitz said.

He did, however, flag one case of a patient relapsing after the 36-week mark -- a case that has raised eyebrows at the meeting.

Lawitz said the drug's makers are not worried that the case will affect development of the drug, other experts said it may raise a red flag about approvals based on relatively short follow-up times.
"I suspect there are, or will be, others," according to Paul Pockros, MD, of the Scripps Clinic in La Jolla, Calif., who was not part of the study. "If it is one-off, the FDA will say it's fine, but if there are more, it could negatively affect" approvals for all of the new direct-acting agents, Pockros told a reporter.

Until recently, drug studies in hepatitis C used relatively long follow-ups, but in 2011, the FDA said future trials could use SVR 12 weeks after the end of therapy as an endpoint, because relapse usually occurs within that time.

Among the 10 patients with 48-week data available, there have been no more relapses, Lawitz reported.

The drug combination was well-tolerated. Most reported adverse events were mild and the most common were headache, fatigue, nausea, and dry skin. No patient stopped therapy because of adverse events.

There were two cases of transient bilirubin elevation, which took place during the first week of therapy but returned to normal with continued treatment.

The study was sponsored by Abbott Laboratories.
Several authors are employees of the company, which took part in data interpretation and approval of the presentation.

Primary source: EASL

Source reference:
Lawitz E, et al "A 12-week interferon-free regimen of ABT-450/r, ABT-072, and ribavirin was well tolerated and achieved sustained virologic response in 91% treatment-naïve HCV IL28B-CC genotype-1-infected subject" EASL 2012.