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Schering-Plough Completes Enrollment of Boceprevir Registration Studies in Treatment-Naive and Treatment-Experienced HCV Patients
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KENILWORTH, N.J., Jan. 27 /PRNewswire-FirstCall/ -- Schering-Plough Corporation (NYSE: SGP) today reported that it has completed patient enrollment in the boceprevir HCV SPRINT-2 study, a pivotal Phase III study in treatment-naive patients. Together with the HCV RESPOND-2 study, a pivotal Phase III study in patients who failed prior treatment that completed enrollment in November 2008, the Company has fully enrolled its registration studies for boceprevir, its lead investigational oral hepatitis C protease inhibitor. A total of more than 1,500 patients were enrolled in these studies at U.S. and international sites.
"We believe boceprevir has the potential to be a first-in-class and best-in-class protease inhibitor for treating chronic hepatitis C," said Thomas P. Koestler, Ph.D., executive vice president and president, Schering-Plough Research Institute. "We are very encouraged by the boceprevir study results reported to date and look forward to the completion of these registration studies." The Company expects to complete the studies in mid-2010.
Schering-Plough previously reported Phase II study results from Part I of the HCV SPRINT-1 study in 595 treatment-naive patients with chronic hepatitis C virus (HCV) genotype 1. In that study, a 48-week boceprevir regimen achieved a 75 percent SVR rate in patients who received 4 weeks of PEGINTRON(TM) (peginterferon alfa-2b) and REBETOL(R) (ribavirin, USP) prior to the addition of boceprevir (P/R lead-in, n=103). This represents a near doubling of the 38 percent SVR rate for patients in the control group receiving 48 weeks of PEGINTRON and REBETOL alone (n=104) (ITT).(1,2) In a 28-week boceprevir P/R lead-in regimen, the SVR rate was 56 percent (n=103). Importantly, for patients who received the boceprevir P/R lead-in regimen and had rapid virologic response (RVR), defined as undetectable virus (HCV-RNA) in plasma after 4 weeks of boceprevir treatment, SVR was 94 percent in the 48-week regimen (n=66) and 82 percent in the 28-week regimen (n=66). RVR has been shown to be a reliable predictor for achieving SVR.
Treatment discontinuations for boceprevir patients due to viral breakthrough were fewer in the 28- and 48-week lead-in arms (4 and 5 percent, respectively) compared to the no lead-in arms (7 and 12 percent, respectively). 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.
Safety data from the HCV SPRINT-1 study showed that the most common adverse events reported in the boceprevir arms were fatigue, anemia, nausea and headache. The incidence of skin adverse events (rash or pruritus) observed in the boceprevir arms was comparable to that seen in the PEGINTRON and REBETOL control arm.
About the Boceprevir Phase III Registration Studies
The two randomized, double-blind, placebo-controlled registration studies evaluate boceprevir in combination with PEGINTRON and REBETOL compared to standard of care with PEGINTRON and REBETOL alone. The HCV SPRINT-2 study evaluates the efficacy of 28- and 48-week regimens of boceprevir (800 mg TID) in combination with PEGINTRON (1.5 mcg/kg/week) and REBETOL (600-1400 mg/day) compared to a control of PEGINTRON and REBETOL alone for 48 weeks in treatment-naive adult patients with chronic HCV genotype 1. The study enrolled a total of 1,099 patients, including 158 African-American/Black patients. The HCV RESPOND-2 study evaluates 36- and 48-week regimens of boceprevir in combination with PEGINTRON and REBETOL at the same doses as described above compared to a control of PEGINTRON and REBETOL alone for 48 weeks in adult patients with chronic HCV genotype 1 who failed prior treatment (relapsers and nonresponders) with peginterferon and ribavirin combination therapy. The study enrolled a total of 404 patients. In both studies, RVR criteria at 4 weeks of boceprevir treatment (treatment week 8) is used to determine which boceprevir patients can stop all treatment at 28 weeks (HCV SPRINT-2) or 36 weeks (HCV RESPOND-2).
For more information about these ongoing registration studies, please visit www.clinicaltrials.gov, search term boceprevir.
About Hepatitis C
Hepatitis C is a serious and potentially life-threatening disease. It is the most common blood-borne infection in America and Europe, and the most common form of liver disease, affecting nearly 5 million people in the United States, 5 million in Europe and some 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.
About PEGINTRON
In the United States, PEGINTRON is indicated for use in combination with ribavirin in patients 3 years of age or older, and as monotherapy in patients 18 years of age and older, for the treatment of chronic hepatitis C in patients with compensated liver disease who have not been previously treated with interferon alpha.
Important Safety Information Regarding U.S. Labeling for PEGINTRON and REBETOL
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 greater than 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 less than 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 6 months post-treatment. Patients should use at least two effective forms of contraception and have monthly pregnancy tests during therapy and for 6 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 6 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 (more than 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 (more than 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 less than or equal to 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 hallucinations, bipolar disorder, mania, encephalopathy (usually elderly treated with higher doses of PEGINTRON), hypotension, tachycardia, retinopathy including macular edema, retinal hemorrhage, cotton wool spots, papilledema, 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, hepatic failure, increases in serum creatinine in patients with renal insufficiency, acute hypersensitivity (angioedema, bronchoconstriction, anaphylaxis and cutaneous eruptions) and hypertriglyceridemia.
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 important full U.S. prescribing information and the Medication Guide for PEGINTRON at www.schering-plough.com.
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 press release includes certain "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including statements relating to the plans for, the potential of and the potential market for boceprevir. 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 uncertainties in the regulatory process, 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 third quarter 2008 10-Q, filed Oct. 29, 2008.
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. Intention-To-Treat (ITT) analysis includes any patient who has taken at least one dose of any study drug.
SOURCE Schering-Plough Corporation
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