In the past, some HCV-positive people may have undergone treatment with standard therapy but did not recover from this infection. Researchers refer to such people as "non-responders." People with HCV genotype 1 are traditionally the least responsive to therapy.

In the Respond 2 study, researchers compared two strategies for trying to increase recovery from HCV infection. Participants were divided into the following three groups:

• Group 1 (control): 4 weeks of therapy with peginterferon + ribavirin, followed by 44 weeks of peginterferon + ribavirin + placebo, for a total of 48 weeks of therapy. After this, participants were monitored for an additional 24 weeks. At the end of 24 weeks of monitoring, they were then assessed for HCV viral load.
• Group 2 (boceprevir + standard therapy): 4 weeks of therapy with peginterferon + ribavirin, followed by 44 weeks of boceprevir + peginterferon + ribavirin, for a total of 48 weeks of therapy. After this, participants were monitored for an additional 24 weeks. At the end of this period, they were then assessed for HCV viral load.
• Group 3 (boceprevir response-guided therapy): 4 weeks of peginterferon + ribavirin, followed by 32 weeks of boceprevir + peginterferon + ribavirin, for a total of 36 weeks of therapy. At the end of 36 weeks, if HCV viral load was undetectable, therapy was discontinued and participants were monitored for 36 more weeks. If at the end of the initial 36 weeks of therapy HCV viral load was still detectable, participants received 12 more weeks of peginterferon + ribavirin. At the end of this time, therapy was stopped and participants were monitored for 24 more weeks and then assessed for HCV viral load.

The average profile of participants who entered the Respond 2 study was as follows:

• age -- 43 years
• 35% females, 65% males
• HCV genotypes 1a and 1b were common
• 90% of participants had an HCV viral load greater than 800,000 IUs/ml
• 35% of participants were described as non-responders to prior HCV therapy and the remaining 65% had relapsed under previous therapy

Boceprevir was taken at a dose of 800 mg three times daily.

Results -- Sustained Virologic Response (SVR)

Overall, SVRs were distributed among the three treatment groups as follows:

• Group 1 (control; peginterferon + ribavirin): 21% achieved an SVR while 32% relapsed
• Group 2 (boceprevir + standard therapy): 66% achieved an SVR while 12% relapsed
• Group 3 (boceprevir response-guided therapy): 59% achieved an SVR while 15% relapsed

Results -- SVR According to the HCV Detectability at Week 8

• Group 1 (control; peginterferon + ribavirin): 100% of participants whose viral load was undetectable achieved an SVR, while 12% of participants whose viral load was detectable achieved an SVR
• Group 2 (boceprevir + standard therapy): 88% of participants whose viral load was undetectable achieved an SVR, while 40% of participants whose viral load was detectable achieved an SVR
• Group 3 (boceprevir response-guided therapy): 88% of participants whose viral load was undetectable achieved an SVR, while 43% of participants whose viral load was detectable achieved an SVR

Overall, boceprevir increased the chances of participants achieving an SVR.

Results -- According to Response to Prior Therapy

Among non-responders to previous peginterferon + ribavirin, here is the proportion who achieved an SVR in the present study:

• Group 1 (control): 7%
• Group 2 (boceprevir + peginterferon + ribavirin): 52%
• Group 3 (boceprevir response-guided therapy): 40%

Among people who relapsed when previously treated with peginterferon + ribavirin, here is the proportion who achieved an SVR in the present study:

• Group 1 (control): 29%
• Group 2 (boceprevir + peginterferon + ribavirin): 75%
• Group 3 (boceprevir response-guided therapy): 69%

Results -- According to Changes in HCV Viral Load at Week 4

In boceprevir studies, including the present one, for the first four weeks of therapy participants received peginterferon + ribavirin. The purpose of this lead-in phase of peginterferon is to assess participants' ability to respond to peginterferon and assess any changes in HCV viral load. Among participants in the present study whose HCV viral loads fell by at least one log after the first four weeks of therapy (in other words, who had a significant response to peginterferon), SVRs were as follows:

• Group 1 (control; peginterferon + ribavirin): 25%
• Group 2 (boceprevir + peginterferon + ribavirin): 79%
• Group 3 (boceprevir response-guided therapy): 73%

Results -- Safety

One death occurred during the Respond 2 study in a person who received boceprevir.

Most side effects were evenly distributed across all three groups, except for these which were more common among boceprevir users:

• anemia
• altered sense of taste

Anemia occurred as follows:

• Group 1 (control; peginterferon + ribavirin): 20%
• Group 2 (boceprevir + peginterferon + ribavirin): 46%
• Group 3 (boceprevir response-guided therapy): 43%

Altered sense of taste occurred in the following proportion of participants:

• Group 1 (control; peginterferon + ribavirin): 11%
• Group 2 (boceprevir + peginterferon + ribavirin): 43%
• Group 3 (boceprevir response-guided therapy): 45%

Summary

The use of boceprevir significantly increased the changes of SVR even in participants who had not previously responded to peginterferon therapy. Both strategies of boceprevir use (response-guided and taking it for 44 weeks) seemed equally effective in people whose previous treatment with peginterferon + ribavirin had failed.

As in other studies, boceprevir was associated with an increased risk of anemia and altered sense of taste in the present study.

Reference

1. Bacon BR, Gordon SC, Lawitz E, et al. HCV Respond-2 Final Results: High sustained virologic response among genotype 1 previous non-responders and relapsers to peginterferon/ribavirin when re-treated with boceprevir plus Pegintron (peginterferon alfa-2b)/ribavirin. In: Program and abstracts of the 61st Annual Meeting of the American Association for the Study of Liver Diseases, 29 October - 2 November, 2010, Boston, MA.