KENILWORTH, N.J., Oct. 15 /PRNewswire-FirstCall/ -- Schering-Plough today announced that data on boceprevir, an investigational hepatitis C virus (HCV) protease inhibitor, will be reported in an oral presentation at the American Association for the Study of Liver Diseases (AASLD) Annual Meeting in Boston, Oct. 30-Nov. 3. Researchers will present sustained virologic response (SVR) data on boceprevir triple combination therapy in treatment-naive HCV genotype 1 patients who had a null response to peginterferon and ribavirin (defined as <1 log decrease in HCV viral load) in the 4-week lead-in arms of the Phase II SPRINT-1 study. Patients with null response to peginterferon and ribavirin are considered to be among the most difficult to treat successfully.
Phase III registration studies with boceprevir in treatment-naive HCV patients and those who failed prior treatment have been fully enrolled and are expected to be completed in mid-2010.
In addition, a late-breaker oral presentation on narlaprevir (SCH 900518), a next-generation once-daily HCV protease inhibitor, will report week-4 rapid virologic response (RVR) and week-12 early virologic response (EVR) data in treatment-naive HCV genotype 1 patients from the ongoing NEXT-1 study. Narlaprevir is currently in Phase II clinical development.
Several presentations will report results with PEGINTRON(R) (peginterferon alfa-2b) and REBETOL(R) (ribavirin, USP) combination therapy, an approved treatment regimen for chronic hepatitis C. These include a late-breaker oral presentation on a genome-wide analysis of patients from the IDEAL study that identified the first genetic marker that may predict a patient’s response to peginterferon and ribavirin combination therapy for hepatitis C. Peginterferon and ribavirin are expected to remain the backbone of HCV treatment regimens for the next several years. Schering-Plough is in the process of analyzing options for the development of a genetic test based on this marker and for making it widely accessible to providers, patients and diagnostic companies for the advancement of science and for helping physicians and patients make more informed treatment decisions.
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 and Europe.
For program information, please visit the AASLD Web site at www.aasld.org.
This document is intended for trade media attending AASLD for their planning purposes.
Key Data Presentations at AASLD 2009
Boceprevir Oral Presentation
High Sustained Virologic Response (SVR) in Genotype 1 (G1) Null Responders to Peg-Interferon alfa-2b plus Ribavirin When Treated with Boceprevir Combination Therapy; P.Y. Kwo et al. Abstract 62. Sunday, Nov. 1, 5:00 pm to 5:15 pm, Hynes Auditorium
Boceprevir Poster Presentations
Response-Guided Therapy (RGT) for Boceprevir Combination Treatment - Results from HCV SPRINT-1; P.Y. Kwo et al. Abstract 1582. Tuesday, Nov. 3, 8:00 am to 1:00 pm, Hynes Exhibit Hall C
Clonal analysis of mutations selected in the HCV NS3 protease domain of genotype 1 non-responders sequentially treated with boceprevir and/or pegylated interferon alfa-2b; J. Vermehren et al. Abstract 1592. Tuesday, Nov. 3, 8:00 am to 1:00 pm, Hynes Exhibit Hall C
Narlaprevir (SCH 900518) Late-Breaker Oral Presentation Once-Daily Narlaprevir (SCH 900518) in Combination with PEGINTRON (Peginterferon alfa-2b)/ Ribavirin) for Treatment-Naive Subjects with Genotype-1 CHC: Interim Results from NEXT-1, a Phase 2a Study; J.M. Vierling et al. Abstract LB4. Monday, Nov. 2, 5:30 pm to 5:45 pm, Hynes Auditorium
Narlaprevir (SCH 900518) Poster Presentation
SVR Results in Chronic Hepatitis C Genotype 1 Patients Dosed with SCH 900518 and Peginterferon Alfa-2b for 2 Weeks, Followed by Peginterferon Alfa-2b and Ribavirin for 24/48 Weeks: An Interim Analysis; J. de Bruijne et al. Abstract 1555. Tuesday, Nov. 3, 8:00 am to 1:00 pm, Hynes Exhibit Hall C
IDEAL Study Late-Breaker Oral Presentation
Genome-wide analysis of patients from the IDEAL study identifies a polymorphism upstream of the IL28B gene that is strongly associated with SVR in patients with HCV-1; A.J. Thompson et al. Abstract LB5. Monday, Nov. 2, 5:45 pm to 6:00 pm, Hynes Auditorium
IDEAL Study Oral Presentation
Relationship of the Use of Statins and Elevated Low-Density Lipoprotein (LDL) or Total Cholesterol (TC) to Virologic Response in Patients Treated for Hepatitis C Virus (HCV) in the IDEAL Study; S.A. Harrison et al. Abstract 120. Monday, Nov. 2, 4:15 pm to 4:30 pm, Hynes Ballroom B
IDEAL Study Poster Presentation
Analysis of Reasons for Treatment Ineligibility in the IDEAL study: African Americans (AA) vs. non-African Americans (non-AA); M. Melia et al. Abstract 848. Sunday, Nov. 1, 8:00 am to 5:30 pm, Hynes Exhibit Hall C
PEGINTRON Oral Presentation
Interim analysis of a controlled trial of pre-transplant peginterferon alfa-2b/ribavirin (PEG/RBV) to prevent recurrent hepatitis C virus (HCV) infection after liver transplantation (LT) in the Adult-to-Adult Liver Transplantation (A2ALL) Study; G.T. Everson et al. Abstract 1. Sunday, Nov 1, 8:00 am to 8:15 am, Hynes Auditorium
About PEGINTRON
PEGINTRON is indicated for use in combination with REBETOL (ribavirin) for the treatment of chronic hepatitis C in patients 3 years of age and older with compensated liver disease.
The following points should be considered when initiating therapy with PEGINTRON in combination with REBETOL: (1) These indications are based on achieving undetectable HCV RNA after treatment for 24 or 48 weeks and maintaining a Sustained Virologic Response (SVR) 24 weeks after the last dose. (2) Patients with the following characteristics are less likely to benefit from re-treatment after failing a course of therapy: previous nonresponse, previous pegylated interferon treatment, significant bridging fibrosis or cirrhosis, and genotype 1 infection. (3) No safety and efficacy data are available for treatment of longer than one year.
PEGINTRON is also indicated for use alone for the treatment of chronic hepatitis C in patients with compensated liver disease previously untreated with interferon alpha and who are at least 18 years of age.
The following points should be considered when initiating therapy with PEGINTRON alone: Combination therapy with REBETOL is preferred over PEGINTRON monotherapy unless there are contraindications to, or significant intolerance of, REBETOL. Combination therapy provides substantially better response rates than monotherapy.
Important Safety Information on PEGINTRON
WARNING: RISK OF SERIOUS DISORDERS AND RIBAVIRIN-ASSOCIATED EFFECTS
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.
Use with Ribavirin: Ribavirin may cause birth defects and death of the unborn child. Extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients. Ribavirin causes hemolytic anemia. The anemia associated with REBETOL therapy may result in a worsening of cardiac disease. Ribavirin is genotoxic and mutagenic and should be considered a potential carcinogen.
Contraindications
PEGINTRON is contraindicated in patients with known hypersensitivity reactions such as urticaria, angioedema, bronchoconstriction, anaphylaxis, Stevens-Johnson syndrome and toxic epidermal necrolysis to interferon alpha or any other component of the product, autoimmune hepatitis, and hepatic decompensation (Child-Pugh score >6 [class B and C]) in cirrhotic CHC patients before or during treatment. PEGINTRON/REBETOL combination therapy is additionally contraindicated in women who are pregnant or may become pregnant (see Boxed Warning and Pregnancy section), men whose female partners are pregnant, patients with hemoglobinopathies (e.g., thalassemia major, sickle-cell anemia), and patients with creatinine clearance <50 mL per min.
Pregnancy
REBETOL therapy should not be started until a report of a negative pregnancy test has been obtained immediately prior to planned initiation of therapy. Extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients during therapy and six months post-treatment. Patients should use at least two effective forms of contraception and have monthly pregnancy tests during therapy and for six months after completion of therapy. If this drug is used during pregnancy or if a patient becomes pregnant, the patient should be apprised of the potential hazard to a fetus. A Ribavirin Pregnancy Registry has been established to monitor maternal-fetal outcomes of pregnancies in female patients and female partners of male patients exposed to ribavirin during treatment, and for six months following cessation of treatment. Physicians and patients are encouraged to report such cases by calling 1-800-593-2214.
Incidence of Adverse Events
Most common adverse reactions (>40%) in adult patients receiving either PEGINTRON or PEGINTRON/REBETOL are injection site inflammation/reaction, fatigue/asthenia, headache, rigors, fevers, nausea, myalgia, and anxiety/emotional lability/irritability. Most common adverse reactions (>25%) in pediatric patients receiving PEGINTRON/REBETOL are pyrexia, headache, neutropenia, fatigue, anorexia, injection site erythema, and vomiting.
In a study with PEGINTRON/REBETOL (weight-based) combination therapy in adult patients, anemia with weight-based dosing was 29%; however, the majority of these cases were mild and responded to dose reductions. The incidence of serious adverse reactions reported for the weight-based REBETOL group was 12%. In many but not all cases, adverse reactions resolved after dose reduction or discontinuation of therapy. Some patients experienced ongoing or new serious adverse reactions during the 6-month follow-up period. Discontinuations for adverse events were 15% and were related to known interferon effects of psychiatric, systemic (e.g., fatigue, headache), or gastrointestinal adverse reactions. Dose modifications due to adverse reactions occurred in 29% of patients.
Most common adverse reactions with PEGINTRON/REBETOL (weight-based) combination therapy were psychiatric, which occurred among 68-69% of patients. These psychiatric adverse reactions included most commonly depression, irritability, and insomnia, each reported by approximately 30-40% of subjects in all treatment groups. Suicidal behavior (ideation, attempts, and suicides) occurred in 2% of all patients during treatment or during follow-up after treatment cessation. PEGINTRON induced fatigue or headache in approximately two-thirds of patients, with fever or rigors in approximately half of the patients. The severity of some of these systemic symptoms (e.g., fever and headache) tends to decrease as treatment continues. There was a 23-24% incidence overall for injection site reactions or inflammation.
Individual serious adverse reactions occurred at a frequency equal to or less than 1% and included suicide attempt, suicidal ideation, severe depression; psychosis, aggressive reaction, relapse of drug addiction/overdose; nerve palsy (facial, oculomotor); cardiomyopathy, myocardial infarction, angina, pericardial effusion, retinal ischemia, retinal artery or vein thrombosis, blindness, decreased visual acuity, optic neuritis, transient ischemic attack, supraventricular arrhythmias, loss of consciousness; neutropenia, infection (sepsis, pneumonia, abscess, cellulitis); emphysema, bronchiolitis obliterans, pleural effusion, gastroenteritis, pancreatitis, gout, hyperglycemia, hyperthyroidism and hypothyroidism, autoimmune thrombocytopenia with or without purpura, rheumatoid arthritis, interstitial nephritis, lupus-like syndrome, sarcoidosis, aggravated psoriasis, urticaria, injection site necrosis, vasculitis, and phototoxicity.
Additional serious adverse events included suicide, homicidal ideation, aggressive behavior sometimes directed towards others, hallucinations, bipolar disorders, mania, encephalopathy (usually elderly treated with higher doses of PEGINTRON), hypotension, tachycardia, retinopathy including macular edema, retinal hemorrhage, cotton wool spots, papilledema, serous retinal detachment, ischemic and hemorrhagic cerebrovascular events, bone marrow toxicity (cytopenia and very rarely aplastic anemia), thyroiditis, dental and periodontal disorders, hemorrhagic/ischemic colitis, dyspnea, pulmonary infiltrates, pneumonia, interstitial pneumonitis, pulmonary hypertension, hepatic failure, increases in serum creatinine in patients with renal insufficiency, acute hypersensitivity (angioedema, bronchoconstriction, anaphylaxis and cutaneous eruptions), hypertriglyceridemia, and peripheral neuropathy.
During the course of therapy lasting up to 48 weeks in patients ages 3 through 17 years receiving PEGINTRON/REBETOL combination therapy, weight loss and growth inhibition were common.
Please see full prescribing information at http://www.spfiles.com/pipeg-intron.pdf.
About Schering-Plough
Schering-Plough is an innovation-driven, science-centered global health care company. Through its own biopharmaceutical research and collaborations with partners, Schering-Plough creates therapies that help save and improve lives around the world. The company applies its research-and-development platform to human prescription, animal health and consumer health care products. Schering-Plough’s vision is to “Earn Trust, Every Day” with the doctors, patients, customers and other stakeholders served by its colleagues around the world. The company is based in Kenilworth, N.J., and its Web site is www.schering-plough.com.
SCHERING-PLOUGH DISCLOSURE NOTICE: The information in this news release includes certain “forward-looking statements” within the meaning of the Securities Litigation Reform Act of 1995, including statements relating to the Company’s marketed products and investigational agents for hepatitis C. 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 about these and other factors that may impact the forward-looking statements, see Schering-Plough’s Securities and Exchange Commission filings, including Part II, Item 1A. “Risk Factors” in the Company’s second quarter 2009 10-Q, filed July 24, 2009.
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