Interim data from Schering-Plough's narlaprevir Phase IIa study

Schering-Plough Corporation (NYSE: SGP) reported that interim results from an ongoing Phase IIa study of narlaprevir (SCH 900518), its investigational, once-daily protease inhibitor, demonstrated potent antiviral activity in treatment-naive patients with chronic hepatitis C virus (HCV) genotype 1. In the lead-in arms of the study, in which patients received a 4-week lead-in of PEGINTRON(R) (peginterferon alfa-2b) and REBETOL(R) (ribavirin, USP) followed by the addition of narlaprevir, 85-87 percent of patients achieved rapid virologic response (RVR), compared to 58-75 percent of patients in the no lead-in narlaprevir arms and no patients in the PEGINTRON and REBETOL control arm. RVR, defined in this study as undetectable virus (HCV RNA) at week 4 of narlaprevir treatment, is recognized as an important predictor for achieving sustained virologic response. These interim results from the NEXT-1 study were reported in an oral presentation at the American Association for the Study of Liver Diseases (AASLD) Annual Meeting in Boston, Oct. 30-Nov. 3.

"These interim results, while preliminary, are very encouraging, and showed that narlaprevir has potent antiviral activity in hepatitis C," said John Vierling, M.D., professor of medicine and surgery, chief of hepatology, Baylor College of Medicine, Houston, and the lead investigator of the study. "In this study, once-daily narlaprevir greatly improved viral clearance at week 4 of treatment in genotype 1 hepatitis C infection compared to the control group. We look forward to further results from this ongoing study."

Importantly, patients in the lead-in narlaprevir arms also achieved improved rates of early virologic response (EVR), defined as undetectable virus at week 12 of treatment, with 85-87 percent of patients having undetectable virus at week 12 of narlaprevir treatment compared to 17 percent of patients at week 12 in the control arm.

Narlaprevir is a next-generation oral HCV protease inhibitor that achieves once-daily dosing through the use of low-dose ritonavir as a metabolic inhibitor. The NEXT-1 study evaluates 12 weeks of narlaprevir 200 mg or 400 mg once-daily or 100 mg twice daily with low-dose ritonavir (100 mg) in combination with PEGINTRON (1.5 mcg/kg once weekly) and REBETOL (600-1400 mg daily), followed by PEGINTRON and REBETOL alone for an additional 12 or 36 weeks (24 or 48 weeks total). The study includes two treatment arms in which patients receive a 4-week lead-in of PEGINTRON and REBETOL prior to receiving narlaprevir 200 mg or 400 mg once-daily in the above regimen. All patients in the narlaprevir arms have completed narlaprevir dosing. The control arm is PEGINTRON and REBETOL alone for 48 weeks.

In this study, the rate of adverse events in the narlaprevir arms was similar to that in the peginterferon and ribavirin control arm, except for an increase in anemia (there were no discontinuations due to anemia) and an increase in low neutrophil counts (with no clinical sequelae). The most frequently seen adverse events up through 12 weeks of treatment were fatigue, nausea, flu-like illness, headache and insomnia. No increase in skin adverse events (rash or pruritus) beyond what was seen in the peginterferon and ribavirin control was observed.

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