The FINANCIAL — Schering-Plough Corporation (NYSE: SGP) on November 1 reported that a planned interim analysis of a Phase II study showed that boceprevir, its investigational oral hepatitis C protease inhibitor, in combination with peginterferon and ribavirin markedly increased sustained virologic response (SVR) rates with 28 weeks of therapy and nearly doubled SVR with 48 weeks of therapy compared to current standard of care, peginterferon and ribavirin (control group) for 48 weeks.
According to Schering-Plough Corporation, these results from the HCV SPRINT-1 study in 595 treatment-naive patients with chronic hepatitis C virus (HCV) genotype 1 were presented at the 59th American Association for the Study of Liver Diseases (AASLD) Annual Meeting.(1)
In a 48-week boceprevir regimen, the SVR rate was 74 percent at 12 weeks after the end of treatment (SVR 12) in patients who received 4 weeks of PEGINTRON(TM) (peginterferon alfa-2b) and REBETOL(R) (ribavirin, USP) prior to the addition of boceprevir (800 mg TID) (P/R lead-in). In a 28-week boceprevir regimen, the SVR rate was 56 percent at 24 weeks after the end of treatment (SVR 24) in patients who received the P/R lead-in. These results compared to a 38 percent SVR rate (SVR 12) for patients in the control group receiving 48-weeks of PEGINTRON and REBETOL alone (ITT).(2-4)
Importantly, predictability of attaining SVR 12 or 24 based on rapid virologic response (RVR) was greater for boceprevir patients in the lead-in arms compared to the no lead-in arms. In addition, fewer patients in the lead-in arms discontinued treatment due to viral breakthrough. RVR is defined as undetectable virus (HCV-RNA) in plasma on or before week 4 of boceprevir treatment.
"The high response rates seen with boceprevir in this study are very exciting, especially given that genotype 1 is the most common and hardest to treat form of hepatitis C," said Paul Kwo, M.D., associate professor of medicine and medical director, liver transplantation, Department of Medicine, Division of Gastroenterology/Hepatology, Indiana University School of Medicine, Indianapolis, and lead investigator of the study. "Boceprevir was well tolerated by patients in this study, and the use of the 4-week lead-in prior to the addition of boceprevir appears to reduce the incidence of viral breakthrough regardless of treatment duration and may improve SVR over a 48-week treatment period."
The rationale for this novel lead-in treatment regimen is based on the fact that both PEGINTRON and REBETOL reach steady-state concentrations by week 4, so patients have the protease inhibitor added at a time when the backbone drug levels have been optimized. In addition, the patient's immune system will have been activated and primed by PEGINTRON at the time that boceprevir is added to the regimen. This approach may minimize the period of time when there is a "functional monotherapy" with a direct antiviral, potentially reducing the likelihood for the development of resistance.
Safety data from the study showed that the most common adverse events reported in the boceprevir arms were fatigue, anemia, nausea and headache. No increase in skin adverse events (rash or pruritus) was observed in the boceprevir arms beyond what was seen in the PEGINTRON and REBETOL control arm.
Treatment discontinuations due to adverse events were between 9 and 19 percent for patients in the boceprevir arms, compared to 8 percent for the control arm. Treatment discontinuations for boceprevir patients due to viral breakthrough were fewer in the 28- and 48-week lead-in arms (4 and 5 percent, respectively) compared to the no lead-in arms (7 and 11 percent, respectively).