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Merck Grants License to LabCorp for Development of Test To Potentially Identify Patients Likely to Respond to Hepatitis C Therapy

Wed, 07/28/2010 - 12:26am
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Merck Grants License to LabCorp for Development of Test To Potentially Identify Patients Likely to Respond to Hepatitis C Therapy

IL-28B Genetic Polymorphism May Help Predict Patient Response to Peginterferon Alpha-Based Hepatitis C Treatment

WHITEHOUSE STATION, N.J., July 27, 2010 – Merck today announced a non-exclusive license agreement with Laboratory Corporation of America® Holdings (LabCorp®) for the commercialization of a genetic test that may help predict the response of patients with Hepatitis C virus (HCV) infection to peginterferon alpha-based therapy.

LabCorp has developed an in vitro genetic test designed to identify the presence of the IL-28B polymorphism in patients, which studies suggest may be associated with successful response to peginterferon alpha-based therapy, the current standard-of-care in HCV treatment.

“The discovery of a link between the IL-28B polymorphism and response to peginterferon alpha is a scientific finding that may potentially help identify a patient's genetic predisposition for successful response to HCV therapy," said Roger J. Pomerantz, M.D., F.A.C.P., global franchise lead for Infectious Diseases and senior vice president, Merck Research Laboratories. "Viral hepatitis remains a key focus at Merck, and we are committed to seeking solutions that advance patient care, including treatment approaches that are tailored to patient response."

The association of IL-28B polymorphism with peginterferon alpha response was identified by Merck in collaboration with other researchers through a genome-wide association study of nearly 1,700 individuals with HCV genotype 1 who participated in the IDEAL study (Individualized Dosing Efficacy vs. Flat Dosing to Assess OptimaL pegylated interferon therapy), which was sponsored by Merck. The IL-28B association was first reported in a paper published in the journal Nature (September 2009), and the full study manuscript was published in Gastroenterology (May 2010). HCV genotype 1 is the most common form of the virus, accounting for approximately 70 percent of HCV cases in the United States, and is the most difficult to treat.

Under the terms of the agreement, LabCorp will pay a Merck affiliate, a one-time payment and royalties for tests covered under the agreement in exchange for a license to the Merck affiliate’s patent rights covering the detection and use of the IL-28B polymorphism.

Merck intends to provide a limited number of non-exclusive licenses to established diagnostics companies.

Merck's commitment to advancing hepatitis therapy

Merck is committed to building on its strong legacy in the hepatitis field by continuing to discover, develop and deliver vaccines and medicines that prevent and treat viral hepatitis. Extensive research efforts are underway to develop differentiated compounds that bring innovation to hepatitis care.

About PEGINTRON ® (peginterferon alfa-2b)

PEGINTRON is indicated for use in combination with REBETOL® (ribavirin, USP) for the treatment of chronic hepatitis C in patients three 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.

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 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, men whose female partners are pregnant, patients with hemoglobinopathies (eg, 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. 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.

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 >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 (eg, triglycerides >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 REBETOL were depression and suicidal ideation, each occurring at a frequency of less than one percent. The most common fatal events occurring in subjects treated with PEGINTRON and REBETOL were cardiac arrest, suicidal ideation and suicide attempt, all occurring in less than one percent of subjects.

The incidence of serious adverse reactions was comparable between PEGINTRON monotherapy (~12 percent) and PEGINTRON/REBETOL 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 six-month follow-up period. In a study with PEGINTRON/REBETOL (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 REBETOL 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/REBETOL combination therapy and three occurred during the follow-up period but had been on PEGINTRON/REBETOL combination therapy.

Additional serious adverse reactions seen in clinical trials at a frequency of less than or equal to one 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 (>40 percent) 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.

The adverse reaction profile was similar between weight-based and flat-dose PEGINTRON/REBETOL therapies. Weight-based PEGINTRON/REBETOL dosing resulted in increased rates of anemia. Most common adverse reactions with PEGINTRON/REBETOL (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 two 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 /REBETOL 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 (>25 percent) in pediatric patients receiving PEGINTRON/REBETOL 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. 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 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 2009 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 (www.sec.gov).

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