Boceprevir-victrelis-Which pegylated interferon ?

Boceprevir Boosts HCV Response

In HCV treatment failures, SVR was 64% with boceprevir vs. 21%
with placebo, combined with standard therapy, Dr. Steven Flamm said.

"This study clearly establishes that boceprevir seems to have equivalent response with peginterferon 2a as was reported with peginterferon 2b. We await similar data for telaprevir with the peginterferon 2b product, as the registration trials were all done with peginterferon 2a."
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peginterferon 2a = PEGASYS
peginterferon 2b = Peg-Intron

Adding Boceprevir Achieved SVR of 64%

BY PATRICE WENDLING
Elsevier Global Medical News
CHICAGO –

Phase III data indicate that the oral protease inhibitor boceprevir increases antiviral activity when combined with peginterferon alfa-2a and ribavirin in patients with hepatitis C genotype 1 who failed prior therapy.“Boceprevir is the only protease inhibitor that has demonstrated efficacy and safety in phase III trials with both of the commercially available pegylated interferons,” Dr. StevenL. Flamm said at the annual Digestive Disease Week.

Boceprevir (Victrelis) was approved by the Food and Drug Administration in May for the treatment of chronic hepatitis C genotype 1 infection, in combination with peginterferon alfa and ribavirin, in adults with compensated liver disease, including cirrhosis, who are untreated or who failed previous interferon and ribavirin therapy.

Boceprevir was the first protease inhibitor for hepatitis C virus (HCV) to be approved by the FDA, and then later in May,telaprevir (Incivek) received FDA approval.

The addition of boceprevir to peginterferon alfa-2b and ribavirin in the recently reported RESPOND-2 trial resulted in a significantly higher sustained virologic response (SVR) rate for prior nonresponders and virologic relapsers, compared with peginterferon alfa-2b and ribavirin alone (66% vs. 21%, respectively)(N. Engl. J. Med. 2011;364:1207-17).

No studies have been done previously to examine the efficacy and safety of boceprevir in combination with peginterferon alfa-2a (Pegasys) plus ribavirin, explained Dr. Flamm, professor of medicine-hepatology and surgery at Northwestern University Feinberg School of Medicine in Chicago.

There has been much debate about which pegylated interferon should be used in the treatment of HCV infection, wroteDr. Hidenori Toyoda and Dr.Takashi Kumada of Ogaki

( Japan) Municipal Hospital (Expert Opin. Pharmac other. 2009;10:2845-57). Peginterferon alfa-2a has the longer half-life of the two, and is used in a fixed weekly dose, whereas peginterferon alfa-2b is dosed on the basis of weight and is thought to have higher specific antiviral activity.

A head-to-head comparison of the two pegylated interferons in the IDEAL trial showed comparable antiviral activity during the first 12 weeks of treatment when combined with ribavirin in patients with HCV genotype 1 and high viral loads, but discontinuation rates were higher for safety reasons with peginterferon alpha-2b plus ribavirin (6% vs. 1%)( J. Viral Hepat. 2007;14:721-9).

The current study described by Dr.Flamm – the Protocol 05685 trial – used entry criteria identical to those of the RESPOND-2 trial, and randomly assigned202 genotype-1 relapsers and nonresponders to a 4-week lead-in of peginterferon alfa-2a/ribavirin (PEG-2a/R) followed by PEG-2a/R with placebo or boceprevir 800 mg t.i.d. for 44weeks. PEG-2a was administered subcutaneously at 180 mcg/kg once weekly,and ribavirin was given in a divided daily dose of 1,000-1,200 mg/day based on weight.

Patients with detectable HCVRNA at week 12 were discontinued from treatment for futility. One patient was randomized but not treated.The study’s primary end point of SVR rate at week 24 was significantly higher with boceprevir at 64%, compared with21% in the control group (P less than.0001), Dr. Flamm said. Relapse rates with the two regimens were 12% and33%, respectively. “When you compare these to the figures in the RESPOND-2trial that’s already been reported in the same patient population, you see very,very similar findings among SVR and relapse[rates],” he said.

When the data were broken down on the basis of historical response, 47% of prior nonresponders achieved an SVR with boceprevir, vs. only 5% with the control treatment. Relapse rates in these patients were 30% and 67%, respectively.

Among prior relapsers, 70% achieved an SVR with boceprevir, vs. 28% with the control therapy, with relapse rates of6% and 28%. Regardless of historic response,patients with a poor response to interferon, as determined by less than a1 log10 viral load decline after the 4-week lead-in period, fared worse. SVR rates among these patients were 39% in the boceprevir group and 0% in the control group, compared with 71% and 25%, respectively,in patients with at least a 1log10 viral load decline, Dr. Flamm said.

Antiviral activity was also higher among patients with undetectable vs. detectable HCV RNA at weeks 8 and 12.In multivariate stepwise logistic analysis, treatment with boceprevir was“far and away” the strongest factor that predicted an SVR, he said. Other significan tpredictors were previous response/relapser vs. nonresponder, viral load of 800,000 IU or less, and body mass index of 25-30 kg/m2 vs. more than 30 kg/m2.

Patients treated with boceprevir were more likely than controls to experience anemia (50% vs. 33%), nausea (39% vs.27%), neutropenia (31% vs. 18%), dysgeusia(39% vs. 15%), diarrhea (25% vs.7%), and rash (23% vs. 7%). These adverse effects were at least 10% more frequent in the boceprevir arm than in the control arm, Dr. Flamm said. “Boceprevir and pegylated interferon-2a and ribavirin therapy was well tolerated, and no new safety findings were observed in comparison to boceprevir and pegylated interferon-2b and ribavirin,” Dr. Flamm said.

The study was sponsored by Merck,maker of boceprevir. Dr. Flamm reported financial relationships with numerous pharmaceutical companies,including Merck. Several of his coauthors reported financial relationships,including employment, with Merck.

It is important to establish whether both boceprevir and telaprevir work equally well with both of the pegylated interferons.

This study clearly establishes that boceprevir seems to have equivalent response with peginterferon2a as was reported with peginterferon 2b. We await similar data for telaprevir with the peginterferon 2b product, as the registration trials were all done with peginterferon 2a.

ROBERT S. BROWN JR., M.D.,AGAF, is the Frank Cardile Professor of Medicine and Surgery and Chief of the Center for Liver Disease and Transplantation,Columbia University College of Physicians and Surgeons, New York.