Boceprevir Active, Well-Tolerated in Treatment-Naive Patients With HCV-1: Presented at EASL

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Title: Boceprevir Active, Well-Tolerated in Treatment-Naive Patients With HCV-1: Presented at EASL
URL: http://www.pslgroup.com/dg/2205E2.htm
Doctor's Guide
April 29, 2008

By Emma Hitt, PhD

MILAN, Italy -- April 29, 2008 -- Boceprevir in combination with pegylated interferon (PEG-IFN) alfa-2b and ribavirin (RBV) for 28 weeks produces a higher sustained viral response (SVR) rate in treatment-naive patients with hepatitis C virus (HCV) genotype 1 compared with historical controls who are treated without boceprevir, according to findings reported here at the 43rd Annual Meeting of the European Association for the Study of the Liver (EASL 2008).

Paul Kwo, MD, Clinical Assistant Professor, Department of Medicine, in the Division of Gastroenterology/Hepatology, Indiana University School of Medicine, Indianapolis, Indiana, presented the findings here on April 26.

The results were from a planned interim analysis of the phase 2 HCV Serine Protease Inhibitor Therapy-1 (SPRINT-1) trial, which includes 6 treatment arms, 5 of them containing boceprevir. Two arms are comparing boceprevir for 24 weeks versus 48 weeks in combination with PEG-IFN alfa-2b/RBV; 2 arms will compare a 4-week, lead-in phase with PEG-IFN alfa-2b/RBV versus initiation of boceprevir triple therapy on day 1. Arm 5 contains low-dose RBV, and arm 6 is a control arm of 48 weeks of PEG-IFN alfa-2b/RBV.

The current analysis compares a 4-week PEG-IFN alfa-2b/RBV lead-in phase followed by 24 weeks of boceprevir 800 mg TID (n = 103) versus 28 weeks of boceprevir 800 mg TID with no lead-in phase (n = 107). Both arms also include PEG-IFN alfa-2b 1.5 mcg/kg/week and RBV 800 to 1400 mg/day with boceprevir.

The rationale for including a PEG-IFN alfa-2b/RBV lead-in phase is based on the idea that both drugs reach steady-state concentrations by week 4; thus, with a lead-in phase, patients receive boceprevir when backbone drug levels have been optimised and the patient's immune system has been activated.

After 4 weeks of treatment, HCV RNA was undetectable in 60% of the lead-in arm and 39% of the no-lead-in arm compared with 8% of the PEG-IFN alfa-2b/RBV control arm (n = 104). At week 12, HCV RNA was undetectable in 78% and 73% of the 2 boceprevir arms, respectively, compared with 34% of the control arm.

At week 28, the final time point for this interim analysis, the SVR rates were similar for the lead-in (57%) and no-lead-in (55%) arms. Data for the control arm were not available, but the findings with boceprevir are superior to those observed with PEG-IFN alfa-2b/RBV for 48 weeks in historical controls, Dr. Kwo noted.

The predictability of attaining SVR at 12 weeks if HCV RNA was undetectable after 4 weeks of boceprevir treatment was 85% for the lead-in arm and 74% for the no-lead-in arm. Relapse rates were comparable in patients completing 28 weeks of treatment in the lead-in (18%) versus the no-lead-in (19%) arms. In addition, patients with undetectable HCV RNA after 4 weeks of boceprevir were less likely to relapse at week 28.

Boceprevir was generally well tolerated, although the rate of discontinuations overall was higher in the boceprevir arms (26% for the lead-in arm and 28% in the no-lead-in arms) compared with the PEG-IFN alfa-2b/RBV control arm (14%).

Fatigue, anaemia, and taste disorders were higher with boceprevir than with control treatment, but no increased incidence of rash or severity of rash with boceprevir was observed, and most haemoglobin reductions were mild.

"As we gain experience with all of these new hepatitis C drugs, including boceprevir, we will learn how to better manage their side effects, much as we did when peg/ribavirin came into the clinic," Dr. Kwo said.

Final results from the HCV SPRINT-1 study are anticipated to become available early next year. The study is currently ongoing at sites across the United States, Canada, and Europe.

Funding for this study was provided by Schering-Plough.

[Presentation title: Interim Results From HCV SPRINT-1: RVR/EVR From Phase 2 Study of Boceprevir Plus Pegintron(TM) (Peginterferon Alfa-2b)/Ribavirin in Treatment-Naive Subjects With Genotype-1 CHC. Abstract 995]

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