EASL: Boceprevir Plays Well With Interferon Drugs

By Walter Alexander, Contributing Writer, MedPage Today Published: April 02, 2011
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner

BERLIN -- Boceprevir, an investigational protease inhibitor for hepatitis C virus (HCV) infection, is effective against genotype 1 of the virus irrespective of the particular type of pegylated interferon alfa drug with which it is combined, a researcher said here.

In two studies just published in the New England Journal of Medicine, triple therapy including boceprevir (Victrelis) improved outcomes both in previously untreated patients and in those with inadequate responses to standard therapy, in comparison with standard two-drug therapy.

But both studies used peginterferon alfa-2b along with ribavirin as two-drug regimen, leaving open the question of whether boceprevir would be equally effective when used with peginterferon alfa-2a, the other major type of interferon drug for HCV.

In a late-breaking poster presentation here at the European Association for the Study of the Liver (EASL) annual meeting, a researcher from Northwestern University in Chicago reported response rates with "PEG2a" and boceprevir in prior nonresponders that were similar to those seen in the so-called RESPOND-2 trial reported in the NEJM with the 2b version.

"PEG2a is used throughout the world, too," the researcher, Steven Flamm, MD, told MedPage Today. "This is the first large-scale trial to look at boceprevir with PEG2a. It's important to establish that boceprevir also works with this other pegylated product."

The study he reported involved 201 patients with HCV genotype 1 who had relapsed or failed to maintain responses with previous interferon and ribavirin therapy.

They were randomized in a 2:1 ratio to two arms: 134 to receive a four-week lead-in of pegylated interferon alfa-2a and ribavirin with boceprevir then added for 44 weeks, and 67 to a control regimen with the same schedule but with placebo in place of boceprevir.

Patients with detectable HCV-RNA at week 12 were discontinued from treatment for futility. The study's primary endpoint was sustained viral response at 24-weeks post therapy.

Significantly more patients achieved a sustained response in the boceprevir group: 64% versus 21% in the control group (P<0.0001), nearly identical to the RESPOND-2 findings. The relapse rate was higher in the control group, at 33% versus 12% (P not reported).

Flamm also reported that viral response at eight weeks (defined as undetectable HCV RNA) strongly predicted a sustained response. In patients with early responses, sustained response rates were 89% with boceprevir versus 44% in the control group.

On the other hand, sustained response rates were poorer for patients failing to achieve undetectable viral load at eight weeks, with rates of 42% with boceprevir and 16% in the control group.

Compared with the control group, patients in the boceprevir arm were about twice as likely to suffer serious anemia or neutropenia, with higher rates of erythropoietin use as well.

Discontinuations and dose modifications because of adverse events were more common among patients taking boceprevir. But futility by week 12 was even more common in the control group.

As a result, the overall proportion of patients remaining on treatment at week 20 was substantially lower in the control arm -- 31% versus 72% -- and the median duration of treatment was 334 days in the boceprevir group compared with 105 days for controls.

Flamm underscored that HCV genotype 1 is the most common and least responsive form of HCV, and that in this population the standard-of-care treatment is usually a failure. "Many of these people are desperate, and there's nothing else we can do for them until we have a new treatment," he said.

He concluded, "Boceprevir is safe and effective with both peginterferon alfa-2a and 2b."

Mark Thursz, MD, a hepatologist at Imperial College in London and vice-secretary of EASL, told MedPage Today that the 2a form is the more commonly used peginterferon in Great Britain and Europe.

"It was necessary to show that boceprevir works with both interferons," he said.

The study was supported by Merck.

Flamm reported relationships with Amgen, Genzyme, and Schering-Plough (now Merck). Several co-authors were Merck employees.

Thursz declared he had no relevant financial relationships.

Primary source: European Association for the Study of the Liver
Source reference:
Flamm S, et al "High sustained virologic response (SVR) among genotype 1 previous non-responders and relapsers to peginterferon/ribavirin when re-treated with boceprevir (BOC) plus peginterferon alfa-2a/ribavirin" EASL 2011; Abstract 4.

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