Boceprevir directly inhibits the HCV NS3 protease, which is essential for viral replication.1
Two randomised, placebo-controlled double-blind phase 3 studies evaluated the efficacy of boceprevir in the treatment of chronic HCV genotype 1 infection, the most common form of the disease. Added to the current standard of care (pegylated interferon plus ribavirin), boceprevir 800mg 3 times daily significantly increased sustained virologic response rates (defined as an undetectable HCV RNA level after 24 weeks of follow-up) in both studies.
SPRINT-2 enrolled 1097 previously untreated patients, who were randomised to 1 of 3 treatment arms.2 Patients in all 3 arms underwent a 4-week lead-in period on peginterferon alfa-2b and ribavirin alone. The control group then received add-on placebo for 44 weeks, while the other 2 groups were assigned to add-on boceprevir for either 44 or 24 weeks. Treatment in the 24-week group was guided by response, with patients who had a detectable HCV RNA level between weeks 8 and 24 switching to placebo plus peginterferon alfa-2b and ribavirin for another 20 weeks.
Among non-black patients (n=938), sustained virologic response rates for boceprevir plus peginterferon and ribavirin were significantly greater than for placebo plus peginterferon and ribavirin: 68% (44 weeks’ treatment) and 67% (24 weeks’ treatment) versus 40% (p<0.001 for both). Black patients (n=159), who typically show a poorer response to HCV treatment, exhibited corresponding response rates of 53% (p=0.004), 42% (p=0.04) and 23%, respectively. Overall, treatment with boceprevir increased the likelihood of a sustained virologic response more than three-fold (p<0.001).2
RESPOND-2 enrolled 403 patients who had previously relapsed or failed to respond to peginterferon plus ribavirin.3 As in SPRINT-2, all participants underwent a 4-week lead-in period on peginterferon alfa-2b and ribavirin. Patients then received either additional placebo for 44 weeks, or boceprevir for 44 or 32 weeks; those in the 32-week group who had a detectable HCV RNA level at week 8 (but not at week 12) received placebo plus peginterferon and ribavirin for an additional 12 weeks.
Sustained virologic response rates were similar in patients who received 44 or 32 weeks of boceprevir (66% and 59%, respectively) and significantly higher with boceprevir than placebo (21%; p<0.001 for both).3
Adverse events most commonly associated with boceprevir were fatigue, nausea, headache, anaemia and dysgeusia.1 In SPRINT-2, anaemia necessitated dose reduction in 13% of control patients and 21% of boceprevir recipients, and discontinuation in 1% and 2%, respectively.1
In a pooled analysis of the two phase 3 studies, resistance-associated HCV amino acid variants were detected in 15% of boceprevir-treated patients and in 53% of those who did not achieve a sustained virologic response.1
- Victrelis Summary of Product Characteristics, July 2011.
- Poordad F et al. N Engl J Med 2011; 364: 1195–1206.
- Bacon BR et al. N Engl J Med 2011; 306: 1207–17.
Further information: Merck Sharp & Dohme Ltd