Schering-Plough Announces Hepatitis C Data Presentations At Digestive Disease Week (DDW) 2007 Annual Meeting

Main Category: Liver Disease / Hepatitis
Also Included In: Conferences;  Clinical Trials / Drug Trials
Article Date: 19 May 2007 - 0:00 PDT

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A total of 20 oral and poster presentations on clinical studies with Schering-Plough's hepatitis products, including PEGINTRON(TM) (peginterferon alfa-2b) and REBETOL(R) (ribavirin, USP) combination therapy for chronic hepatitis C virus (HCV) infection, as well as boceprevir (SCH 503034), the company's investigational oral HCV protease inhibitor currently in Phase II clinical development, will be presented by leading researchers at the 38th annual Digestive Disease Week (DDW) meeting to be held at the Washington Convention Center in Washington, D.C., May 20-23.

Hepatitis C is the most common blood-borne infection in America and the most common form of liver disease, affecting nearly 5 million people in the United States and 200 million people worldwide. It is the leading cause of cirrhosis and liver cancer, and the number one reason for liver transplants in the United States.

PEGINTRON

Clinical investigators will present findings at DDW from numerous PEGINTRON studies evaluating patient response to therapy at certain treatment milestones, an approach that is aimed at individualizing treatment for patients. Schering-Plough also is exploring novel therapeutic approaches with PEGINTRON in combination with investigational antiviral agents to optimize treatment for patients with more difficult-to-treat forms of the disease, such as patients who were nonresponders to previous therapy.

Boceprevir (SCH 503034)

Schering-Plough is undertaking a large, fully integrated clinical development program for its oral HCV protease inhibitor boceprevir, with the goal of developing new strategies for improving treatment outcomes for patients with hepatitis C.

At DDW, Schering-Plough will present results of in vitro studies conducted in collaboration with Wyeth/ViroPharma of boceprevir in combination with their investigational non-nucleoside HCV polymerase inhibitor HCV-796.

In Addition, Schering-Plough has initiated the HCV SPRINT-1 study (HCV Serine Protease Inhibitor Therapy-1), a large Phase II study with boceprevir ongoing at sites across the U.S., Canada and Europe. The primary objective of the study is to evaluate the safety and efficacy of boceprevir (800 mg TID) in combination with PEGINTRON (1.5 mcg/kg once weekly) and REBETOL (800-1400 mg daily) in the HCV genotype 1 treatment-naive patient population. The first part of the study (screening cohort 1) has completed enrollment and involves more than 500 patients in five treatment arms. A second part to the study (screening cohort 2) recently opened for patient enrollment and adds two additional treatment arms. This second cohort will evaluate the safety and efficacy of boceprevir in combination with PEGINTRON and a lower dose of REBETOL (400-1000 mg daily). In total, approximately 550-600 patients will be enrolled in the HCV SPRINT-1 study.

Schering-Plough also is conducting a large Phase II study evaluating the safety and efficacy of boceprevir in combination with PEGINTRON and REBETOL in patients chronically infected with HCV genotype 1 who were null responders to previous peginterferon and ribavirin combination therapy (i.e., patients who did not achieve undetectable HCV-RNA or a 2 log decline in viral load with a minimum of 12 weeks of peginterferon and ribavirin combination therapy). This represents a very difficult-to-treat patient population for which there is a great unmet medical need. The study involves approximately 350 patients and is ongoing at centers in the United States and Europe. All study participants have completed treatment with boceprevir in combination with PEGINTRON (1.5 mcg/kg once weekly) and REBETOL (800-1400 mg daily) and are in the follow-up phase of the study. Data from this study will be available later in 2007, and will help guide future clinical development of boceprevir.

Key Oral Presentations at DDW

Favorable Cross-Resistance Profile of HCV-796 and Boceprevir (SCH-503034) and Enhanced Anti-Replicon Activity Mediated By Combination Treatment; R. Ralston, Monday, May 21, 11:15 a.m., Room 206

Pharmacodynamic Analysis of the Antiviral Activity of the Non-Nucleoside Polymerase Inhibitor, HCV-796, in Combination With Peginterferon Alfa-2b in Treatment-Naive Patients With Chronic HCV; E.S. Maller, Monday, May 21, 2:15 p.m., Room 206

Phase II Study of celgosivir in combination with Peginterferon alfa-2b and ribavirin in chronic hepatitis C genotype 1 nonresponder patients; K.D. Kaita, Monday, May 21, 2:45 p.m., Room 206

Schering-Plough Sponsored CME Symposium

"HCV Treatment Decisions: Challenging Issues"

Monday, May 21, 6:30-8:30 pm, Grand Hyatt Washington,

Independence Ballroom A, 1000 H Street, NW, Washington, D.C.

This case-based symposium is designed to outline effective management strategies for patients with hepatitis C virus infection. Optimizing HCV patient outcome requires a thorough understanding of the underlying patient and disease factors that influence treatment. Clinical scenarios will be presented, and through the use of case studies, the distinguished faculty will review and discuss current data to illustrate their respective treatment decisions.

About PEGINTRON and REBETOL Combination Therapy

PEGINTRON is approved in the United States for use alone or with ribavirin (800 mg/day) for the treatment of chronic hepatitis C in patients with compensated liver disease who have not been previously treated with interferon alpha and who are at least 18 years of age.

WARNING

Alpha interferons, including PEGINTRON, may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Patients should be monitored closely with periodic clinical and laboratory evaluations. Patients with persistently severe or worsening signs or symptoms of these conditions should be withdrawn from therapy. In many but not all cases these disorders resolve after stopping PEGINTRON therapy.

Ribavirin causes hemolytic anemia. Anemia associated with REBETOL therapy may exacerbate cardiac disease that has led to fatal and nonfatal myocardial infarctions. Patients with a history of significant or unstable cardiac disease should not be treated with REBETOL. It is advised that complete blood counts (CBC) be obtained at baseline and at weeks 2 and 4 of therapy or more frequently if clinically indicated.

REBETOL and combination REBETOL/PEGINTRON therapy must not be used by women, or male partners of women, who are or may become pregnant during therapy and during the 6 months after stopping therapy. REBETOL and combination REBETOL/PEGINTRON therapy should not be initiated until a report of a negative pregnancy test has been obtained immediately prior to initiation of therapy. Women of childbearing potential and men must use effective contraception (at least two reliable forms) during treatment and during the 6- month post-treatment follow-up period. Significant teratogenic and/or embryocidal effects have been demonstrated for ribavirin in all animal species in which adequate studies have been conducted. These effects occurred at doses as low as one twentieth of the recommended human dose of REBETOL.

PEGINTRON

There are no new adverse events specific to PEGINTRON as compared to INTRON(R) A (Interferon alfa-2b, recombinant) for Injection; however, the incidence of some (e.g., injection site reactions, fever, rigors, nausea) were higher. The most common adverse events associated with PEGINTRON were "flu- like" symptoms, occurring in approximately 50 percent of patients, which may decrease in severity as treatment continues. Application site disorders were common (47 percent), but all were mild (44 percent) or moderate (4 percent) and no patient discontinued, and included injection site inflammation and reaction (i.e., bruise, itchiness, irritation). Injection site pain was reported in 2 percent of patients receiving PEGINTRON. Alopecia (thinning of the hair) is also often associated with alpha interferons including PEGINTRON.

Psychiatric adverse events, which include insomnia, were common (57 percent) with PEGINTRON but similar to INTRON A (58 percent). Depression was most common at 29 percent. Suicidal behavior including ideation, suicidal attempts, and completed suicides occurred in 1 percent of patients during or shortly after completing treatment with PEGINTRON.

PEGINTRON/REBETOL is contraindicated in patients with autoimmune hepatitis, decompensated liver disease, and in patients with hemoglobinopathies (e.g., thalassemia major, sickle-cell anemia).

The following serious or clinically significant adverse events have been reported at a frequency less than 1 percent with PEGINTRON or interferon alpha: severe decreases in neutrophil or platelet counts, hypothyroidism, hyperglycemia, hypotension, arrhythmia, ulcerative and hemorrhagic colitis, development or exacerbation of autoimmune disorders including thyroiditis, RA, systemic lupus erythematosus, psoriasis, pulmonary disorders (dyspnea, pulmonary infiltrates, pneumonitis and pneumonia, some resulting in patient deaths), urticaria, angioedema, bronchoconstriction, anaphylaxis, retinal hemorrhages, and cotton wool spots.

In the PEGINTRON/REBETOL combination trial the incidence of serious adverse events was 17 percent in the PEGINTRON/REBETOL groups compared to 14 percent in the INTRON A/REBETOL group. The incidence of severe adverse events in the PEGINTRON/REBETOL combination therapy trial was 23 percent in the INTRON A/REBETOL group and 31-34 percent in the PEGINTRON/REBETOL groups. Dose reductions due to adverse reactions occurred in 42 percent of patients receiving PEGINTRON (1.5 mcg/kg)/REBETOL and in 34 percent of those receiving INTRON A/REBETOL.

REBETOL should not be used in patients with creatinine clearance less than 50 mL/min.

Schering-Plough is a global science-based health care company with leading prescription, consumer and animal health products. Through internal research and collaborations with partners, Schering-Plough discovers, develops, manufactures and markets advanced drug therapies to meet important medical needs. Schering-Plough's vision is to earn the trust of the physicians, patients and customers served by its approximately 33,500 people around the world. The company is based in Kenilworth, N.J., and its Web site is http://www.schering-plough.com.

SCHERING-PLOUGH DISCLOSURE NOTICE: The information in this press release includes certain "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including statements relating to the company's strategy regarding and the potential of PEGINTRON, REBETOL and boceprevir (SCH 503034). Forward-looking statements relate to expectations or forecasts of future events. Schering-Plough does not assume the obligation to update any forward-looking statement. Many factors could cause actual results to differ materially from Schering-Plough's forward- looking statements, including market forces, economic factors, product availability, patent and other intellectual property protection, current and future branded, generic or over-the-counter competition, the regulatory process, and any developments following regulatory approval, among other uncertainties. For further details of these and other risks and uncertainties that may impact forward-looking statements, see Schering-Plough's Securities and Exchange Commission filings, including Part I, Item 1A, "Risk Factors" in the company's first quarter 2007 10-Q.

Schering-Plough
http://www.schering-plough.com

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