March 07, 2011 10:44 AM Eastern Time
WHITEHOUSE STATION, N.J.--(BUSINESS WIRE)--Merck (NYSE: MRK), known as MSD outside of the United States and Canada, announced today that several new data analyses from Phase III studies of VICTRELIS™ (boceprevir), its investigational oral hepatitis C protease inhibitor, will be presented at The International Liver CongressTM / 46th European Association for the Study of the Liver (EASL) annual meeting. The meeting will be held from March 30 – April 3 in Berlin. In total, more than 20 abstracts highlighting Merck medicines and investigational therapies for chronic hepatitis C virus (HCV) infection will be presented, including 3 oral presentations and 17 posters for VICTRELIS.
Presented for the first time will be final results from a Phase III study of VICTRELIS administered in combination with Pegasys® (peginterferon alfa-2a) and ribavirin in adult patients with chronic HCV genotype 1 infection who were non-responders or relapsers to previous pegylated interferon and ribavirin therapy.
The EASL presentations will also include new analyses of the pivotal Phase III data for VICTRELIS administered in combination with PEGINTRON® (peginterferon alfa-2b) and ribavirin from the HCV SPRINT-2 and HCV RESPOND-2 studies:
• Response-guided therapy with VICTRELIS in combination with current standard therapy among patients with chronic HCV genotype 1, including special populations such as those with advanced fibrosis / cirrhosis;
• Overall safety profile of VICTRELIS administered in combination with current standard therapy for chronic HCV; and
• Potential predictive factors for chronic HCV treatment success, including response following 4 weeks of lead-in therapy and IL28B polymorphism.
The abstracts were published today and can be accessed on the EASL website. For program information, please visit http://www2.kenes.com/liver-congress/Pages/Home.aspx.
VICTRELIS (Boceprevir) Oral Presentations
Parallel Session: HCV Therapy, Thursday, March 31, 17:00 – 19:00, Hall 1
Boceprevir in Addition to Standard of Care Enhanced SVR in Hepatitis C Virus (HCV) Genotype-1 with Advanced Fibrosis/Cirrhosis: Subgroup Analysis of SPRINT-2 and RESPOND-2 Studies; S. Bruno et al. 17:15 – 17:30 CET
Boceprevir Resistance-Associated Variants (RAVS) are Observed More Frequently in HCV (Gt1)-Infected Patients with Poor Response to Peginterferon Alfa-2b/Ribavirin; S. Zeuzem et al. 17:45 – 18:00 CET
IL28B Polymorphism Predicts Virologic Response in Patients with Hepatitis C Genotype 1 Treated with Boceprevir (BOC) Combination Therapy. F. Poordad et al. 18:30 – 18:45 CET
VICTRELIS (Boceprevir) Key Poster Presentations
High Sustained Virologic Response (SVR) Among Genotype 1 Previous Non-Responders and Relapsers to Peginterferon/Ribavirin When Re-Treated With Boceprevir Plus Peginterferon Alfa-2A/Ribavirin. S. Flamm et al. Late-Breaker Abstract 1366. Thursday, March 31.
Response-Guided Therapy with Boceprevir Plus Peginterferon Alfa-2b/Ribavirin Reduces Duration in Naive and Peginterferon Alfa-2b/Ribavirin Previous-Treatment-Failure Patients with HCV Genotype 1. M.P. Manns et al. Abstract 448. Thursday, March 31.
Overall Safety Profile of Boceprevir Plus Peginterferon Alfa-2b/Ribavirin. M.P. Manns et al. Abstract 449. Thursday, March 31.
Four-Week Therapy with Peginterferon Alfa-2b/Ribavirin Effectively Predicts Sustained Virologic Response in Treatment-Naïve and Previous-Treatment-Failure Patients with HCV-1 Treated with Boceprevir Plus Peginterferon Alfa-2b/Ribavirin. J.M. Viering et al. Abstract 481. Thursday, March 31.
Utility of Historical Data Compared to Lead-In Response in Predicting Sustained Virologic Response in Non-Responders and Relapsers to Peginterferon/Ribavirin When Re-Treated With Boceprevir+Peginterferon Alfa-2b/Ribavirin (P/R). R. Esteban et al. Abstract 418. Thursday, March 31.
About the HCV RESPOND-2 and HCV SPRINT-2 Studies
The HCV RESPOND-2 study in treatment-failure patients and the HCV SPRINT-2 study in previously untreated patients each evaluated two treatment strategies with VICTRELIS administered in combination with PEGINTRON and ribavirin to assess the ability to improve sustained virologic response (SVR) 1 and potentially shorten overall treatment duration compared to treatment with PEGINTRON and ribavirin alone:
• Response-guided therapy, in which treatment-failure patients with undetectable virus at week 8 were able to stop all treatment at 36 weeks, and in which previously untreated
• patients with undetectable virus during weeks 8 through 24 were able to stop all treatment at 28 weeks; and
• 48 weeks of treatment (4-week PEGINTRON and ribavirin lead-in followed by the addition of VICTRELIS for 44 weeks).
In both studies, all patients were treated with a 4-week lead-in of PEGINTRON (1.5 mcg/kg/week) and an investigational dose of ribavirin (600-1,400 mg/day), followed by the addition of VICTRELIS (800 mg three times a day).
As previously reported, the U.S. Food and Drug Administration has granted priority review status to the New Drug Application (NDA) for VICTRELIS and the Marketing Authorization Application (MAA) for VICTRELIS has been accepted for accelerated assessment by the European Medicines Agency. Data in the NDA and MAA have been provided in support of the proposed use of boceprevir for the treatment of chronic HCV genotype 1 infection, in combination with peginterferon alpha and ribavirin, in adult patients with compensated liver disease who are previously untreated or who have failed previous therapy.
Merck is committed to building on its strong legacy in the field of viral hepatitis by continuing to discover, develop and deliver vaccines and medicines to help prevent and treat viral hepatitis. In hepatitis C, company researchers developed the first approved therapy for chronic HCV in 1991 and the first combination therapy in 1998. 2011 marks the 10-year anniversary of the introduction of PEGINTRON and ribavirin in combination therapy, a current standard therapy for chronic HCV worldwide. In addition to ongoing studies with VICTRELIS, extensive research efforts are underway to develop additional innovative oral therapies for viral hepatitis care.
About PEGINTRON
PEGINTRON is indicated for use in combination with 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 ribavirin: (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 ribavirin is preferred over PEGINTRON monotherapy unless there are contraindications to, or significant intolerance of, ribavirin. Combination therapy provides substantially better response rates than monotherapy.
Selected 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 ribavirin 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/ribavirin combination therapy is additionally contraindicated in women who are pregnant or may become pregnant, 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
Ribavirin therapy should not be started until a report of a negative pregnancy test has been obtained immediately prior to planned initiation of therapy. 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.
Patients with the following conditions should be closely monitored and may require dose reduction or discontinuation of therapy:
• Hemolytic anemia with ribavirin
• Neuropsychiatric events
• History of significant or unstable cardiac disease
• Hypothyroidism, hyperthyroidism, hyperglycemia, diabetes mellitus that cannot be effectively treated by medication
• New or worsening ophthalmologic disorders
• Ischemic and hemorrhagic cerebrovascular events
• Severe decreases in neutrophil or platelet counts
• History of autoimmune disorders
• Pancreatitis and ulcerative or hemorrhagic/ischemic colitis and pancreatitis
• Pulmonary infiltrates or pulmonary function impairment
• Child-Pugh score greater than 6 (Class B and C)
• Increased creatinine levels in patients with renal insufficiency
• Serious, acute hypersensitivity reactions and cutaneous eruptions
• Dental/periodontal disorders reported with combination therapy
• Hypertriglyceridemia may result in pancreatitis (e.g., triglycerides greater than 1000 mg/dL)
• Weight loss and growth inhibition reported with combination therapy in pediatric patients.
Life-threatening or fatal neuropsychiatric events, including suicidal and homicidal ideation, depression, relapse of drug addiction/overdose, and aggressive behavior, sometimes directed towards others, have occurred in patients with and without a previous psychiatric disorder during PEGINTRON treatment and follow-up.
Adverse Events
Serious adverse reactions have occurred in approximately 12 percent of subjects in clinical trials. The most common serious events occurring in subjects treated with PEGINTRON and ribavirin were depression and suicidal ideation, each occurring at a frequency of less than 1 percent. The most common fatal events occurring in subjects treated with PEGINTRON and ribavirin were cardiac arrest, suicidal ideation, and suicide attempt, all occurring in less than 1 percent of subjects.
The incidence of serious adverse reactions was comparable between PEGINTRON monotherapy (about 12 percent) and PEGINTRON/ribavirin combination therapy weight-based (12 percent) or flat-dose (17 percent). 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. In a study with PEGINTRON/ribavirin (weight-based) combination therapy in adult patients, anemia with weight-based dosing occurred at an increased rate (29 percent vs. 19 percent); however, the majority of these cases were mild and responded to dose reductions. The incidence of serious adverse reactions reported for the weight-based ribavirin group was 12 percent. There were 31 deaths in clinical trials which occurred during treatment or during follow-up. Of the deaths, 19 were patients on either PEGINTRON or PEGINTRON/ribavirin combination therapy and three occurred during the follow-up period but had been on PEGINTRON/ribavirin combination therapy.
Additional serious adverse reactions seen in clinical trials at a frequency of equal to or less than 1 percent included psychosis, aggressive reaction, relapse of drug addiction/overdose; nerve palsy (facial, oculomotor); cardiomyopathy, 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.
Greater than 96 percent of all subjects in clinical trials experienced one or more adverse events. Most common adverse reactions (greater than 40 percent) in adult patients receiving either PEGINTRON or PEGINTRON/ribavirin are injection site inflammation/reaction, fatigue/asthenia, headache, rigors, fevers, nausea, myalgia, and anxiety/emotional lability/irritability.
The adverse reaction profile was similar between weight-based and flat-dose PEGINTRON/ribavirin therapies. Weight-based PEGINTRON/ribavirin dosing resulted in increased rates of anemia. Most common adverse reactions with PEGINTRON/ribavirin (weight-based) therapy were psychiatric, which occurred among 68-69 percent of patients and included depression, irritability, and insomnia, each reported by approximately 30-40 percent of subjects in all treatment groups. Suicidal behavior (ideation, attempts, and suicides) occurred in 2 percent of all patients during treatment or during follow-up after treatment cessation. Other common reactions included injection site reactions, fatigue/ asthenia, headache, rigors, fever, nausea, myalgia, anxiety/emotional lability/irritability. The severity of some of these systemic symptoms tends to decrease as treatment continues.
Subjects receiving PEGINTRON/ribavirin as re-treatment after failing a previous interferon combination regimen reported adverse reactions similar to previous treatment-naïve patients receiving this regimen.
In general, the adverse reaction profile in the pediatric population was similar to that observed in adults. Most common adverse reactions (greater than 25 percent) in pediatric patients receiving PEGINTRON/ribavirin are pyrexia, headache, neutropenia, fatigue, anorexia, injection site erythema, abdominal pain, and vomiting.
Please see full prescribing information at http://www.spfiles.com/pipeg-intron.pdf.
About Merck
Today's Merck is a global healthcare leader working to help the world be well. Merck is known as MSD outside the United States and Canada. Through our prescription medicines, vaccines, biologic therapies, and consumer care and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to healthcare through far-reaching policies, programs and partnerships. For more information, visit http://www.merck.com/.
Forward-Looking Statement
This news release includes “forward-looking statements” within the meaning of the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995. Such statements may include, but are not limited to, statements about the benefits of the merger between Merck and Schering-Plough, including future financial and operating results, the combined company’s plans, objectives, expectations and intentions and other statements that are not historical facts. Such statements are based upon the current beliefs and expectations of Merck’s management and are subject to significant risks and uncertainties. Actual results may differ from those set forth in the forward-looking statements.
The following factors, among others, could cause actual results to differ from those set forth in the forward-looking statements: the possibility that the expected synergies from the merger of Merck and Schering-Plough will not be realized, or will not be realized within the expected time period; the impact of pharmaceutical industry regulation and health care legislation; the risk that the businesses will not be integrated successfully; disruption from the merger making it more difficult to maintain business and operational relationships; Merck’s ability to accurately predict future market conditions; dependence on the effectiveness of Merck’s patents and other protections for innovative products; the risk of new and changing regulation and health policies in the U.S. and internationally and the exposure to litigation and/or regulatory actions.
Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in Merck’s 2010 Annual Report on Form 10-K and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (http://www.sec.gov/).
Please see attached Prescribing Information, Medication Guide, and Instructions for Use including Boxed Warning for PEGINTRON. The Prescribing Information, Medication Guide, and Instructions for Use are also available at http://www.spfiles.com/pipeg-intron.pdf, http://www.spfiles.com/mgpeg-intron.pdf and http://www.spfiles.com/ifupeg-intron.pdf.
Endnote
1 SVR, the protocol specified primary efficacy endpoint, is defined as achievement of undetectable HCV-RNA at 24 weeks after the end of treatment in all randomized patients treated with any study medication. Per protocol, if a patient did not have a 24-week post-treatment assessment, the patient’s 12-week post-treatment assessment was utilized.
VICTRELIS™ and PEGINTRON® are trademarks of Schering Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, N.J., USA
Pegasys® is a trademark of its respective owner and is not a trademark of Merck & Co., Inc., Whitehouse Station, N.J., USA.
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