Drug Trio Works in Low-Response Hepatitis C

Meeting Coverage

Published: Nov 6, 2013

Coverage of Hepatitis C Virus is supported in part by an independent educational grant from AbbVie Pharmaceuticals.

This report is part of a 12-month Clinical Context series.

Action Points

• 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 this uncontrolled study of patients with refractory genotype 2 or 3 HCV demonstrated high efficacy rates when sofosbuvir was added to interferon and ribavirin therapy.
• Be aware that there is great interest in interferon-free regimens given the high adverse event rate associated with this medication.

WASHINGTON -- An unlikely drug combination had high efficacy rates in a hard-to-treat group of patients with hepatitis C virus (HCV) infection, a researcher said here.

After 12 weeks of therapy, the combination -- sofosbuvir, pegylated interferon, and ribavirin -- led to viral cure rates of 89%, according to Eric Lawitz, MD, of the University of Texas Health Science Center in San Antonio.

Patients in the study were regarded as hard to treat because they had genotype 2 and 3 disease, had failed previous therapy with interferon and ribavirin, and many had cirrhosis, Lawitz said at the annual meeting of the American Association for the Study of Liver Diseases.

The standard current therapy is interferon and ribavirin, combined with one of two approved protease inhibitors that target the virus itself -- telaprevir (Incivek) and boceprevir (Victrelis).

Sofosbuvir remains investigational but it has mainly been tested in combination with ribavirin alone, as part of the movement to get rid of the highly toxic interferon.

The drug has been recommended for approval, with different indications depending on HCV genotype. An FDA advisory panel suggested it be used with interferon and ribavirin in genotype 1 patients, but with ribavirin alone in genotypes 2 and 3.

But it seems unlikely the drug will often be used in combination with interferon and ribavirin, commented Donald Jensen, MD, of the University of Chicago, who was not involved in the study but who moderated the session at which it was presented.

"Certainly, the field is moving toward an interferon-free world." he told MedPage Today. But there might still be cases in which an interferon-based regimen might be used as a "fallback," he added.

"If you have a genotype 3 patient with cirrhosis who had failed therapy with sofosbuvir and ribavirin," he said, interferon might be added to a retreatment regimen.

The study "shows you can use it," he said.

In a single-arm study, Lawitz and colleagues enrolled 47 patients for 12 weeks of therapy with the three drugs. The primary endpoint was undetectable virus 12 weeks after the end of therapy (SVR₁₂).

The overall SVR₁₂ rate was 89%, with 22 of the 23 genotype 2 patients reaching the endpoint and 20 of 24 genotype 3 patients -- 96% and 83% respectively.

Lawitz reported that one genotype 2 patient was noncompliant with the medication and stopped treatment early.

Two genotype 3 patients also stopped early -- one lost to follow-up and one because of an adverse event -- while two others completed therapy but relapsed before the end of the 12-week follow-up.

SVR₁₂ rates were similar between cirrhotic and non-cirrhotic patients, Lawitz reported.

Almost all patients reported some adverse events, "not unexpectedly in an interferon-based regimen," Lawitz said, adding the adverse event profile was consistent with the known side effects of interferon and ribavirin.

The most common events were flu-like symptoms, fatigue, anemia, neutropenia, and nausea, Lawitz reported.

The study was supported by Gilead Sciences. Lawitz reported financial links with AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Idenix Pharmaceuticals, Intercept Pharmaceuticals, Janssen, Merck, Novartis, Presidio, Roche, Santaris Pharmaceuticals, Vertex Pharmaceuticals, Kadmon, Achillion Pharmaceuticals, BioCryst, Biotica, Enanta, Idenix, and Theravance. Several authors are employees of Gilead.

Jensen reported financial links with Abbott, Roche/Genentech, Vertex, GlobeImmune, Boehringer-Ingelheim, and Tibotec.

Primary source: American Association for the Study of Liver Diseases
Source reference: Lawitz E, et al "Sofosbuvir in combination with pegIFN and ribavirin for 12 weeks provides high SVR rates in HCV-infected genotype 2 or 3 treatment experienced patients with and without compensated cirrhosis: Results from the LONESTAR-2 study"AASLD 2013; Abstract LB-4.

Source