25 Nov 2008
The company reported for the first time that in a Phase II study, a 48-week boceprevir regimen achieved an unprecedented 75 percent sustained virologic response (SVR) rate at 24 weeks after the end of treatment (SVR 24) in patients who received 4 weeks of PEGINTRON (peginterferon alfa-2b) and REBETOL(R) (ribavirin) prior to the addition of boceprevir (800 mg TID) (P/R lead-in).
This represents a near doubling of the 38 percent SVR 24 rate for patients in the control group receiving 48-weeks of PEGINTRON and REBETOL alone.
In a 28-week boceprevir P/R lead-in regimen, the SVR 24 rate was 56 percent.
Importantly, for patients who received the boceprevir P/R lead-in regimen and had rapid virologic response (RVR), defined as undetectable virus in plasma after 4 weeks of boceprevir treatment, SVR was 94 percent in the 48 week regimen and 82 percent in the 28-week regimen. RVR has been shown to be a reliable predictor for achieving SVR. These final results are from the HCV SPRINT-1 study in 595 treatment-naive patients with chronic hepatitis C virus (HCV) genotype 1.
Full results of the boceprevir HCV SPRINT-1 study and early phase clinical results with SCH 900518 are being submitted for presentation at a future medical meeting.
About the Boceprevir HCV SPRINT-1 Study
In this Phase II study, known as HCV SPRINT-1 , boceprevir (800 mg TID) was evaluated in three treatment regimens:
* 4 weeks of PEGINTRON (1.5 mcg/kg once weekly) and REBETOL (800-1400 mg daily based on patient weight) followed by the addition of boceprevir to the combination for 24 or 44 weeks (totaling 28 or 48 weeks of treatment)
* boceprevir in combination with PEGINTRON and REBETOL at the doses described above for 28 or 48 weeks
and in Part II of the study,
* boceprevir in combination with PEGINTRON and low-dose REBETOL (400-1000 mg daily based on patient weight) for 48 weeks
compared to a control of
* PEGINTRON (1.5 mcg/kg once weekly) and REBETOL (800-1400 mg daily based on patient weight) alone for 48 weeks.
The primary endpoint of the study is SVR after 24 weeks of follow up (SVR 24). SVR rates are not yet available for the Part II of this study evaluating boceprevir with low-dose REBETOL (n=59) compared to contemporaneous control (n=16) as described above.
About Boceprevir Phase III Studies
Schering-Plough is conducting two large ongoing pivotal Phase III studies of boceprevir in patients chronically infected with HCV genotype 1. One study is in treatment-naive patients and the other in patients who failed prior treatment (relapsers and nonresponders). The two randomized, double-blind, placebo-controlled studies evaluate the efficacy of boceprevir in combination with PEGINTRON and REBETOL compared to standard of care with PEGINTRON and REBETOL alone.
The study in treatment-naive patients is known as HCV SPRINT-2
The study in patients who failed prior treatment is known as HCV RESPOND-2
The two studies are expected to enroll a total of more than 1,400 patients at U.S. and international sites.
For more information about these ongoing Phase III studies, please visit www.clinicaltrials.gov, search term boceprevir.
Next-Generation HCV Protease Inhibitor SCH 900518
As part of its long-term commitment to hepatitis C therapy, Schering-Plough also is developing SCH 900518 ("518"), a next-generation HCV protease inhibitor. A Phase IIa study with 518, known as the NEXT-1 study, is currently ongoing. The company said that 518 has been shown to be 10 times more potent in-vitro than other protease inhibitors currently in Phase III development and has the potential for once daily dosing. 518 also has shown decreased emergence of resistance in vitro. Given its pharmacokinetic (PK) profile, the company anticipates that 518 may be active against some HCV strains that are resistant to other protease inhibitors. Phase I proof of concept studies with 518 in treatment-naive patients and those who failed prior treatment, both as monotherapy and in combination with peginterferon (without ribavirin), demonstrated enhanced antiviral activity, with up to 4 log10 and 5 log10 decreases in circulating HCV, respectively.
Endnotes
1. SVR, the protocol specified primary efficacy endpoint, is defined as achievement of undetectable HCV-RNA at 24 weeks after the end of treatment. Per protocol, if a patient does not have a 24-week post-treatment assessment, the patient's 12-week post-treatment assessment will be utilized.
2. Intention-To-Treat (ITT) analysis includes any patient who has taken at least one dose of any study drug.
Schering Plough Corporation http://www.schering-plough.com
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