KENILWORTH, N.J., Aug. 4 Schering-PloughCorporation (NYSE: SGP) today reported top-line results from a planned interimanalysis of a Phase II study of boceprevir, its investigational oral hepatitisC protease inhibitor. The analysis showed a high rate of sustained virologicresponse (SVR) in patients receiving boceprevir-based combination therapy inthis study of 595 treatment-naïve patients with chronic hepatitis C virus(HCV) genotype 1.
In a 48-week treatment regimen, the SVR rate at 12 weeks after the end oftreatment (SVR 12) was 74 percent (ITT) in patients who received 4 weeks ofPEGINTRON(TM) (peginterferon alfa-2b) and REBETOL(R) (ribavirin, USP) prior tothe addition of boceprevir (800 mg TID) (P/R lead-in), compared to 38 percentfor patients in the control group receiving 48-weeks of PEGINTRON and REBETOLalone.(1-3)
Patients in the study who received 48-weeks of boceprevir in combinationwith PEGINTRON and REBETOL from the beginning of treatment (no P/R lead-in)achieved 66 percent SVR 12.
In the two 28-week boceprevir arms of the study, SVR at 24 weeks after theend of treatment (SVR 24) was 56 percent and 55 percent for patients in thelead-in and no lead-in arms, respectively.
Importantly, for patients who received the PEGINTRON and REBETOL lead inand had rapid virologic response (RVR), defined as undetectable virus(HCV-RNA) in plasma after 4 weeks of boceprevir treatment, SVR (ITT) was 82percent in the 28-week regimen and 92 percent in the 48 week regimen.
"These top-line results with boceprevir are very exciting, especiallygiven that genotype 1 is the most common and hardest to treat form ofhepatitis C," said Paul Kwo, M.D., associate professor of medicine and medicaldirector, liver transplantation, Department of Medicine, Division ofGastroenterology/Hepatology, Indiana University School of Medicine,Indianapolis, and lead investigator of the study. "Boceprevir was welltolerated by patients in this study, including those who received 48 weeks ofboceprevir in the longer duration treatment arms."
Safety data from the study showed that the most common adverse eventsreported in the boceprevir arms were fatigue, anemia, nausea and headache. Noincrease in skin adverse events (rash or pruritus) beyond what was seen in thePEGINTRON and REBETOL control arm was observed. Treatment discontinuationsdue to adverse events were between 9 and 19 percent for patients in theboceprevir arms, compared to 8 percent for the control arm.
In the study, known as HCV SPRINT-1 (HCV Serine Protease InhibitorTherapy-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 dailybased on patient weight) therapy followed by the addition of boceprevir to thecombination for 24 or 44 weeks (totaling 28 or 48 weeks of treatment);boceprevir in combination with PEGINTRON and REBETOL at the doses describedabove for 28 or 48 weeks; and boceprevir in combination with PEGINTRON andlow-dose REBETOL (400-1000 mg daily) for 48 weeks, compared to a control ofPEGINTRON (1.5 mcg/kg once weekly) and REBETOL (800-1400 mg daily based onpatient weight) alone for 48 weeks (an approved treatment regimen). Theprimary endpoint of the study is SVR after 24 weeks of follow up (SVR 24).This is an ongoing study and SVR 24 rates are not yet available for patientsin the 48-week boceprevir arms or the 48-week control arm of the study.
P/R Lead-in equals PEGINTRON and REBETOL for 4 weeks prior to the additionof boceprevir
"These top-line results further validate this novel treatment paradigm andthe design of our pivotal Phase III studies of boceprevir, one intreatment-naive patients and one in patients who had failed prior treatment,in which all patients will receive 4 weeks of PEGINTRON and REBETOL prior tothe addition of boceprevir," said Thomas P. Koestler, Ph.