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Roche Files for Application with FDA to Market Pegasys for Chronic Hepatitis B Treatment
  - CDC Estimates 1.25 Million in U.S. are Chronically Infected with Hepatitis B --
Phase III Study:
STUDY PRESENTED AT 39th EASL Conferecnce, Berlin, Germany, April, 2004
--72-week results from a Phase III, partially double-blind study
Pegasys plus Lamivudine vs Pegasys Monotherapy vs Lamivudine
Study reports responses in 550 treatment-naïve patients with chronic hepatitis B.: ALT normalization, necroinflammatory activity, fibrosis, HBV DNA response, response by genotype (A, B, C, D), adverse event profiles, withdrawal rates, depression rates.
This report includes discussion about HBV—occult HBV, serum markers, epidemiology, clinical treatment goals, combination therapy.
NUTLEY, N.J., July 21 /PRNewswire/ -- Roche announced today the submission of a supplemental new biologics license application (sBLA) with the U.S. Food and Drug Administration to market Pegasys(R) (peginterferon alfa-2a) for the treatment of chronic hepatitis B (CHB). Simultaneously, Roche has also filed with the European Medicines Agency to market Pegasys for this indication in the European Union. Pegasys received FDA approval for the treatment of chronic hepatitis C in October 2002 and today is the most prescribed chronic hepatitis C medication in the U.S.
"Hepatitis B is a serious public health threat worldwide and can be deadly if left untreated," said Salvatore Badalamente, M.D., Medical Director, Roche. "We are committed to offering Pegasys as a new option to the millions of people throughout the world who are chronically infected with hepatitis B."
Roche submitted this filing based on Pegasys data from its comprehensive clinical development program in hepatitis B. This program involved more than 1,500 chronic hepatitis B patients from three separate studies. A phase II study compared Pegasys to standard interferon in patients with HBeAg-positive disease. Two phase III studies compared Pegasys to Epivir-HBV(R) (lamivudine) in patients with HBeAg-positive disease and in patients with HBeAg-negative disease (a more difficult to treat mutation of the hepatitis B virus), respectively. The two studies are the largest trials conducted to date in the patient populations infected with either variation of hepatitis B.
"Each year an estimated 5,000 to 6,000 people die in the United States because of chronic hepatitis B liver disease. We recognize the need for new hepatitis B treatment options and commend Roche for its extensive research to advance hepatitis B therapy," said Alan Brownstein, President and Chief Executive Officer, American Liver Foundation.
"This filing demonstrates Roche's continued focus on research to advance the field of hepatology. For example, this year, publications and data were presented from Pegasys and Copegus studies in difficult-to-treat hepatitis C populations including African Americans and patients co-infected with hepatitis C and HIV," said Dr. Badalamente.
About Chronic Hepatitis B
The National Center for Infectious Diseases of the Centers for Disease Control estimates that 1.25 million people in the United States are chronically infected with hepatitis B. Chronic hepatitis B can lead to cirrhosis, hepatocellular carcinoma, and death. In the U.S., the most common modes of transmission of the hepatitis B virus are through sexual and blood-to-blood contact, although the disease can also be transmitted from pregnant women to their infants. The number of new infections in the U.S. has decreased in recent years, in part due to the introduction of the hepatitis B vaccine in 1982.
About Pegasys for Hepatitis C
Pegasys, a pegylated alpha interferon, and Copegus are indicated for use in combination for the treatment of adults with chronic hepatitis C who have compensated liver disease and have not previously been treated with interferon alpha. Patients in whom efficacy was demonstrated included patients with compensated liver disease and histological evidence of cirrhosis.
Pegasys is dosed at 180mcg as a subcutaneous injection taken once a week. Copegus is available as a 200mg tablet, and is administered orally two times a day as a split dose.
Roche has backed Pegasys with the most extensive clinical research program ever undertaken in hepatitis C, with major studies initiated to advance treatment for hepatitis C patients with unmet needs, including patients co-infected with HIV and HCV, African Americans, patients with cirrhosis, patients with normal ALT levels, and patients who have failed to respond to previous therapy.
Please see attached additional information about Pegasys indication and safety.
Facts About Pegasys (Peginterferon alfa-2a) in Combination with Copegus
* Pegasys(R), a pegylated alpha interferon, alone or in combination with Copegus(R) (ribavirin, USP) is indicated for the treatment of adults with chronic hepatitis C who have compensated liver disease and have not previously been treated with interferon alpha. Patients in whom efficacy was demonstrated included patients with compensated liver disease and histological evidence of cirrhosis (Child-Pugh class A).
Dosing and Administration
* Pegasys, a premixed solution, is dosed at 180mcg as a subcutaneous injection once a week. Copegus, available as a 200mg tablet, is administered at 800 to 1200mg taken twice daily as a split dose. The two products are sold separately.
Combination Therapy Clinical Studies
* The two combination therapy pivotal study findings:

* Study 5, including 1,284 patients receiving medication, showed that patients with certain genotypes (strains) of the hepatitis C virus should be treated with different dosing regimens of Pegasys and Copegus. The treatment regimens and resulting sustained virological response rates for these groups treated with Pegasys and Copegus therapy were:
-- Genotype 1: 48 week duration with 1000 - 1200mg Copegus: 51 percent
-- Genotype non-1: 24 week duration with 800mg Copegus: 82 percent
* Study 4, published in the September 26, 2002 New England Journal of Medicine, including 1,121 patients receiving medication, showed that Pegasys and Copegus combination therapy is a more effective treatment for chronic hepatitis C than interferon alfa-2b and ribavirin. The sustained virological response rate in the Pegasys and Copegus treated patients was 53 percent compared to 44 percent in the interferon alfa-2b and ribavirin group. Sustained virological response refers to a patient's continued undetectable serum hepatitis C RNA levels 24 weeks after finishing a course of treatment.
The Future -- Special Populations, HIV/HCV Co-infection
* Pegasys and Copegus studies have been conducted to evaluate the therapy for the treatment of African-Americans, who have a substantially higher prevalence of hepatitis C infection and typically have lower response rates to hepatitis C therapy than Caucasian Americans.
-- Data from the study showed a 26 percent SVR in African American patients compared to a 39 percent SVR for Caucasian patients.
* Trials have also been conducted to evaluate Pegasys and Copegus treatment in patients co-infected with hepatitis C and HIV and in patients with hepatitis C who failed to achieve a sustained virological response to standard interferon and ribavirin.
-- Data from this study showed the highest SVR ever achieved among co-infected patients.
Adverse Events
* Alpha interferons, including Pegasys, 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. Therapy should be withdrawn in patients with persistently severe or worsening signs or symptoms of these conditions. In many, but not all cases, these disorders resolve after stopping Pegasys therapy (see CONTRAINDICATIONS, WARNINGS, PRECAUTIONS and ADVERSE EVENTS in complete product information).
* Use with Ribavirin. Ribavirin, including Copegus may cause birth defects and/or death of the fetus. 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 worsening of cardiac disease.Ribavirin is genotoxic, mutagenic, and should be considered a potential carcinogen (see CONTRAINDICATIONS, WARNINGS, PRECAUTIONS and ADVERSE EVENTS in complete product information).
* Pegasys is contraindicated in patients with hypersensitivity to Pegasys or any of its components, autoimmune hepatitis, and decompensated hepatic disease (Child-Pugh class B and C) before or during treatment with Pegasys. Pegasys is also contraindicated in neonates and infants because it contains benzyl alcohol. Benzyl alcohol has been reported to be associated with an increased incidence of neurological and other complications in neonates and infants, which are sometimes fatal.
Pegasys and Copegus therapy is additionally contraindicated in patients with a hypersensitivity to Copegus or any of its components, women who are pregnant, men whose female partners are pregnant, and patients with hemoglobinopathies (eg, thalassemia major, sickle-cell anemia).
* COPEGUS THERAPY SHOULD NOT BE STARTED UNLESS A REPORT OF A NEGATIVE PREGNANCY TEST HAS BEEN OBTAINED IMMEDIATELY PRIOR TO INITIATION OF THERAPY. Women of childbearing potential and men must use two forms of effective contraception during treatment and during the six months after treatment has concluded. Routine monthly pregnancy test must be performed during this time. If pregnancy should occur during treatment or during six months post-therapy, the patient must be advised of the significant teratogenic risk of Copegus therapy to the fetus.Physicians and patients are strongly encouraged to report any pregnancies that do occur to Roche by calling 1-800-526-6367.
* The most common adverse events reported for Pegasys and Copegus combination therapy, observed in clinical trials (n=451), were fatigue/asthenia (65%), headache (43%), pyrexia (41%), myalgia (40%), irritability/anxiety/nervousness (33%), insomnia (30%), alopecia (28%), neutropenia (27%), nausea/vomiting (25%), rigors (25%), anorexia (24%), injection site reaction (23%), arthralgia (22%), depression (20%), pruritus (19%) and dermatitis (16%).
* Serious adverse events include neuropsychiatric disorders (suicidal ideation and suicide attempt), serious and severe bacterial infections, bone marrow toxicity (cytopenia and rarely, aplastic anemia), cardiovascular disorders (hypertension, arrhythmias and myocardial infarction), hypersensitivity (including anaphylaxis), endocrine disorders (including thyroid disorders and diabetes mellitus), autoimmune disorders (including psoriasis and lupus), pulmonary disorders (dyspnea, pneumonia, bronchiolitis obliterans, interstitial pneumonitis and sarcoidosis), colitis (ulcerative and hemorrhagic/ischemiccolitis), pancreatitis, and opthalmologic disorders (decrease or loss of vision, retinopathy including macular edema and retinal thrombosis/hemorrhages, optic neuritis and papilledema).
* The complete package inserts for Pegasys and Copegus are available at http://www.pegasys.com, or by calling 1-877-PEGASYS.
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