TOP-LINE RESULTS OF BOCEPREVIR PHASE II STUDY SHOWED HIGH RATE OF SUSTAINED RESPONSE (SVR) IN GENOTYPE 1 TREATMENT-NAIVE HEPATITIS C PATIENTS

• 74 percent of patients achieved SVR 12 with 48-week boceprevir-based combination therapy

• High SVR 24 rate also reported for 28-week boceprevir arm

Schering-Plough Corporation (S-P) today [August 4, 2008] reported
top-line results from a planned interim analysis of a Phase II study of boceprevir, its investigational oral hepatitis C protease inhibitor.

The analysis showed a high rate of sustained virologic response (SVR) in patients receiving boceprevir-based combination therapy in this 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 of treatment (SVR 12) was 74 percent (ITT) in patients who received 4 weeks of PEGINTRON (peginterferon alfa-2b) and REBETOL® (ribavirin, USP) prior to the addition of boceprevir (800 mg TID) (P/R lead-in), compared to 38 percent for patients in the control group receiving 48-weeks of PEGINTRON and REBETOL alone [1-3].

Patients in the study who received 48-weeks of boceprevir in combination with PEGINTRON and REBETOL from the beginning of treatment, (no PegIntron/ribavirin (P/R) lead-in) achieved 66 percent SVR 12.

In the two 28-week boceprevir arms of the study, SVR at 24 weeks after the end of treatment (SVR 24) was 56 percent and 55 percent for patients in the lead-in and no lead-in arms, respectively.

Importantly, for patients who received the PEGINTRON and REBETOL lead in and had rapid virologic response (RVR), defined as undetectable virus (HCV-RNA) in plasma after 4 weeks of boceprevir treatment, SVR (ITT) was 82 percent in the 28-week regimen and 92 percent in the 48 week regimen.

"These top-line results with boceprevir 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, including those who received 48 weeks of boceprevir in the longer duration treatment arms."

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) beyond what was seen in the PEGINTRON and REBETOL control arm was observed. 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.

In the study, known as HCV SPRINT-1 (HCV Serine Protease Inhibitor Therapy-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) therapy 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

• Boceprevir in combination with PEGINTRON and low-dose REBETOL (400-1000 mg daily) 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 (an approved treatment regimen).

The primary 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 patients in the 48-week boceprevir arms or the 48-week control arm of the study.

P/R Lead-in = PEGINTRON and REBETOL for 4 weeks prior to the addition of boceprevir

P/R Control = PEGINTRON and REBETOL alone for 48 weeks

SVR 12 for 48 week arms; SVR 24 for 28 week arms [1-3].

"These top-line results further validate this novel treatment paradigm and the design of our pivotal Phase III studies of boceprevir, one in treatment-naïve patients and one in patients who had failed prior treatment, in which all patients will receive 4 weeks of PEGINTRON and REBETOL prior to the addition of boceprevir," said Thomas P. Koestler, Ph.D., executive vice president and president of Schering-Plough Research Institute. "Additionally, this strategy has the potential to reduce the likelihood of the development of resistance by identifying patients who are responders to interferon and ribavirin prior to their receiving a protease inhibitor."

The rationale for this novel 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.

The HCV SPRINT-1 study was conducted at sites across the United States, Canada and Europe. Overall, 77 percent of the 595 patients in the study were enrolled in the United States. African-Americans represent 16 percent of the patients enrolled and 7 percent of patients in the study are cirrhotic.

Results from the HCV SPRINT-1 study will be submitted for presentation at a major medical conference later this year.

About Boceprevir Phase III Studies

The boceprevir Phase III studies are expected to begin enrolling patients this summer. For more information about the Phase III study of boceprevir in treatment-naïve patients, known as HCV SPRINT-2, and the Phase III study in patients who failed prior treatment, known as HCV RESPOND-2, please visit www.clinicaltrials.gov, search term boceprevir.

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. SVR 12 is defined as undetectable HCV-RNA in plasma at 12 weeks after the end of treatment. The protocol specified primary efficacy endpoint of the HCV SPRINT-1 study is SVR as defined above.

3. Intention-To-Treat (ITT) analysis includes any patient who has taken at least one dose of any study drug.