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DDW 2013: Prior Non-responders Can Achieve Good SVR Rates with Boceprevir Triple Therapy

People previously treated with interferon-based therapy can achieve good results when retreated with boceprevir (Victrelis) triple therapy, according to final results from the PROVIDE study presented at the Digestive Disease Week meeting (DDW 2013) last month in Orlando. Prior relapsers had the best response, but even 41% of prior null responders achieved a cure.

John Vierling from Baylor College of Medicine and colleagues reported final findings from the PROVIDE trial, which included patients from the pegylated interferon/ribavirin standard-of-care control arms in Phase 2 and 3 trials of boceprevir who were treated for at least 12 weeks.

This single-arm, open-label study enrolled 168 genotype 1 chronic hepatitis C patients. Two-thirds were men, more than 80% were white, the mean age was 52 years, 62% had harder-to-treat HCV subtype 1a, and 10% had liver cirrhosis. Categorized by previous treatment outcome, 17% were prior relapsers, 51% were partial responders, and 31% were prior null responders who experienced little or no decline in HCV RNA (< 2 log) with previous interferon-based therapy.

Participants were treated with 800 mg 3-time-daily boceprevir plus 1.5 mcg/kg/week pegylated interferon alfa-2b (PegIntron) and 600-1400 mg/day weight-based ribavirin for up to 44 weeks. People with more than 2 weeks since the end of prior treatment received a 4-week lead-in of pegylated interferon/ribavirin alone before adding boceprevir; 4 patients dropped out during the lead-in and never started triple therapy, leaving 164 who received at least 1 dose of boceprevir.

Results

• The overall sustained virological response rate at 24 weeks post-treatment (SVR24) was 65% for patients who started boceprevir.
• Outcomes differed, however, according to prior treatment response:

o   Prior relapsers: 96%;

o   Prior partial responders: 67%;

o   Prior null responders: 41%.

• The overall relapse rate was 11% (0%, 15%, and 13%, respectively, for prior relapsers, partial responders, and null responders).
• Although response rates for prior partial and null responders were similar in a previously reported interim analysis and the final analysis, the SVR rate for relapsers nearly doubled (56% to 96%), due in part to patients with missing interim results that were available for the final tally.
• 76% of patients who experienced at least a 1 log drop in HCV RNA by the end of the lead-in period went on to achieve SVR, compared to 48% of those with lesser early response.
• 60% of patients with high baseline viral load (HCV RNA > 80,000) achieved SVR versus 81% with low pre-treatment viral load.
• 59% of patients with HCV subtype 1b achieved SVR compared to 68% with subtype 1b.
• 65% of non-cirrhotics and 77% of patients with cirrhosis achieved SVR24.
• 38% of black participants (none of whom were prior relapsers) and 69% of non-black patients achieved SVR.
• The null responder cure rate was significantly higher than SVR rates of around 5% for null responders retreated with pegylated interferon/ribavirin alone in prior studies.
• 60 participants discontinued the study early (including 4 during the lead-in) due to treatment failure (55%), adverse events (23%), or non-medical reasons (22%).
• Boceprevir triple therapy was generally safe and well-tolerated.
• The most common side effects were anemia (49%), dysgeusia or unusual taste sensations (35%), and neutropenia (23%).

"SVR rates with [boceprevir and pegylated interferon/ribavirin] were high in all patient subgroups, even among patients who were documented to be null responders to prior pegylated interferon/ribavirin treatment," the investigators concluded. "The safety profile was similar to that previously reported for [boceprevir and pegylated interferon/ribavirin]."

6/6/13

Reference

JM Vierling, FA Helmond, J Wahl, et al. Sustained Virologic Response (SVR) in Prior Peginterferon/Ribavirin (PR) Treatment Failures After Retreatment With Boceprevir (BOC) PR: Final Results of the Provide Study. Digestive Disease Week (DDW 2013). Orlando, May 18-21, 2013. Abstract 869c.