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Treatment with Pegasys/Copegus Provides Hope for Hepatitis C Patients Whose Infection Did Not Initially Respond to Peg-Intron/Ribavirin

- Response at 12 weeks is a powerful predictor of eventual treatment success -

BOSTON, November 02, 2007 /PRNewswire/ -- Roche today announced final results from the REPEAT study, which demonstrated that treatment with once-weekly PEGASYS(R) (peginterferon alfa-2a) and daily COPEGUS(TM) (ribavirin) for 72 weeks is a promising treatment option for patients whose infection did not respond to previous treatment with another pegylated interferon (Peg- Intron(R), peginterferon alfa-2b) and ribavirin. Further, the results showed that response at 12 weeks was a powerful predictor of the eventual outcome: the majority of patients with undetectable virus at 12 weeks went on to achieve a sustained virological response (SVR) after 72 weeks of treatment, while few patients with detectable virus at 12 weeks achieved SVR. These data were presented in an oral session at the 58th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), being held in Boston, Nov. 2-6.

"One of the greatest areas of need in hepatitis C today is to find solutions for patients who have not seen treatment success with an initial course of therapy. REPEAT is an important study which adds significantly to our knowledge about how to manage these patients, demonstrating that extending treatment with PEGASYS and COPEGUS is a promising option," said Donald Jensen, M.D., Professor of Medicine and Director of the Center for Liver Diseases at the University of Chicago Hospital in Chicago, and lead investigator in REPEAT. "A significant finding from REPEAT is confirmation of the reliability of using a patient's response at 12 weeks as a predictor of treatment success, even in patients with cirrhosis. This means that patients who achieve undetectable virus at 12 weeks can continue treatment with a good likelihood of success. It also means that clinicians can confidently discontinue treatment in patients who do not achieve an early response."

More About the REPEAT Study

Enrolling 950 patients from Europe, North America and Latin America, REPEAT (REtreatment with PEgasys in pATients Not Responding to Peg-Intron Therapy) was designed to explore whether intensified treatment with a higher fixed-dose induction of PEGASYS in combination with COPEGUS and/or longer treatment duration may increase treatment success rates in patients who didn't respond to at least twelve weeks of Peg-Intron/ribavirin combination therapy. Patients were randomized 2:1:1:2 to one of four regimens:

    -- Patients in arms A (n=318) and B (n=158) received PEGASYS 360 mcg/week

       for 12 weeks, followed by 180 mcg/week for a further 60 or 36 weeks,

       respectively

    -- Patients in arms C (n=158) and D (n=316) received PEGASYS 180 mcg/week

       for 72 or 48 weeks, respectively

    -- All patients received COPEGUS (1,000/1,200 mg/day) in combination with

       PEGASYS


    Results showed:


    -- The primary endpoint was met: SVR, defined by undetectable hepatitis C

       virus RNA in the blood six months after the end of treatment, was

       significantly higher for arm A (16 percent) compared to arm D (nine

       percent)

    -- A pooled analysis of the 72-week arms vs. the 48-week arms showed that

       72 weeks of treatment had the biggest impact on success of treatment,

       with a doubling of SVR rate compared to 48 weeks (16 percent vs. eight

       percent).  A pooled analysis of the induction dose arms vs. standard

       dose arms showed that treatment with higher fixed-dose induction for

       this difficult-to-treat patient population did not provide significant

       additional benefit

    -- Response at 12 weeks was a strong predictor of successful treatment

       -- Of patients whose virus was undetectable after 12 weeks of therapy,

          57 percent in the 72-week arms went on to achieve treatment success

          (by comparison, among patients who still had detectable virus after

          12 weeks, only four percent achieved treatment success)

       -- The proportion of patients with undetectable virus at 12 weeks was

          17 percent

"REPEAT exclusively enrolled patients who had not previously responded to pegylated interferon combination therapy, in this case Peg-Intron and ribavirin," continued Dr. Jensen. "These patients are a more difficult-to- treat group than relapsers and those who did not respond at all to treatment with non-pegylated interferons, either alone or with ribavirin. For this reason, results from REPEAT cannot be meaningfully compared to results from trials with a large proportion of patients who were relapsers or who did not respond to treatment with older interferons."

The incidence and types of adverse events and serious adverse events were generally consistent across all the arms, and the frequency of moderate to severe hematologic effects were broadly similar across all arms. Discontinuations for adverse events and lab abnormalities were higher for extended treatment. Patients with cirrhosis had a somewhat higher incidence of adverse events, premature withdrawals and dose modifications. (Please see below for complete safety information about PEGASYS and COPEGUS).

About Hepatitis C

Hepatitis C is a blood-borne infectious disease of the liver and a leading cause of cirrhosis, liver cancer and the need for liver transplants. According to the Centers for Disease Control and Prevention (CDC), an estimated 4.1 million Americans (1.6 percent) have been infected with hepatitis C; 3.2 million are chronically infected. The number of new infections per year has declined from an average of 240,000 in the 1980s to about 26,000 in 2004. CDC estimates the number of hepatitis C-related deaths could increase to 38,000 annually by the year 2010, surpassing annual HIV/AIDS deaths.

About PEGASYS

PEGASYS, in combination with COPEGUS (ribavirin), are indicated for the treatment of adults with chronic hepatitis C who have compensated liver disease and have not previously been treated with interferon alpha. Efficacy has been demonstrated in patients with compensated liver disease and histological evidence of cirrhosis (Child-Pugh class A) and patients with HIV disease that are clinically stable (e.g., antiretroviral therapy not required or receiving stable antiretroviral therapy). In addition, PEGASYS in combination with COPEGUS is the first and only FDA-approved regimen for the treatment of chronic hepatitis C in patients coinfected with hepatitis C and HIV. PEGASYS is the only pegylated interferon indicated for the treatment of adult patients with chronic hepatitis B (HBeAg positive and HBeAg negative chronic hepatitis B who have compensated liver disease and evidence of viral replication and liver inflammation).

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, and patients who have failed to respond to previous therapy.

Important Safety Information about PEGASYS

PEGASYS, alone or in combination with COPEGUS, is indicated for the treatment of adults with chronic hepatitis C virus infection who have compensated liver disease and have not been previously 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).

Alpha interferons, including PEGASYS (Peginterferon alfa-2a), 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 REACTIONS 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 a worsening of cardiac disease. Ribavirin is genotoxic and mutagenic and should be considered a potential carcinogen (see CONTRAINDICATIONS, WARNINGS, PRECAUTIONS and ADVERSE REACTIONS in complete product information).

PEGASYS is contraindicated in patients with hypersensitivity to PEGASYS or any of its components, autoimmune hepatitis, and hepatic decompensation (Child-Pugh score greater than 6; class B and C) in cirrhotic CHC monoinfected patients before or during treatment. PEGASYS is also contraindicated in hepatic decompensation with Child-Pugh score greater than or equal to 6 in cirrhotic CHC patients coinfected with HIV before or during treatment. PEGASYS is also contraindicated in neonates and infants because it contains benzyl alcohol. Benzyl alcohol is 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, in 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 6 months after treatment has concluded. Routine monthly pregnancy tests must be performed during this time. If pregnancy should occur during treatment or during 6 months post-therapy, the patient must be advised of the significant teratogenic risk of COPEGUS therapy to the fetus. Healthcare providers and patients are strongly encouraged to immediately report any pregnancy in a patient or partner of a patient during treatment or during 6 months after treatment cessation to the Ribavirin Pregnancy Registry at 1-800-593-2214.

Chronic hepatitis C (CHC) patients with cirrhosis may be at risk of hepatic decompensation and death when treated with alpha interferons, including PEGASYS. During treatment, patients' clinical status and hepatic function should be closely monitored, and PEGASYS treatment should be immediately discontinued if decompensation (Child-Pugh score .6) is observed.

The most common adverse events reported for PEGASYS and COPEGUS combination therapy observed in clinical trials 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 in hepatitis C trials included neuropsychiatric disorders (homicidal ideation, suicidal ideation, suicide attempt, suicide, psychotic disorder and hallucinations), serious and severe bacterial infections (sepsis), bone marrow toxicity (cytopenia and rarely, aplastic anemia), cardiovascular disorders (hypertension, supraventricular arrhythmias and myocardial infarction), hypersensitivity (including anaphylaxis), endocrine disorders (including thyroid disorders and diabetes mellitus), autoimmune disorders (including idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura, psoriasis, lupus, rheumatoid arthritis and interstitial nephritis), pulmonary disorders (dyspnea, pneumonia, bronchiolitis obliterans, interstitial pneumonitis and sarcoidosis), colitis (ulcerative and hemorrhagic/ischemic colitis), pancreatitis, and ophthalmologic disorders (decrease or loss of vision, retinopathy including macular edema and retinal thrombosis/hemorrhages, optic neuritis and papilledema). Adverse reactions reported during post-approval use of PEGASYS therapy, with and without ribavirin, include hearing impairment, hearing loss, serious skin reactions, including erythema multiforme major, and infections (bacterial, viral and fungal).

About Roche

Hoffmann-La Roche Inc. (Roche), based in Nutley, N.J., is the U.S. pharmaceuticals headquarters of the Roche Group, one of the world's leading research-oriented healthcare groups with core businesses in pharmaceuticals and diagnostics. For more than 100 years in the U.S., Roche has been committed to developing innovative products and services that address prevention, diagnosis and treatment of diseases, thus enhancing people's health and quality of life. An employer of choice, in 2007 Roche was named Top Company of the Year by Med Ad News and one of the Top 20 Employers (Science magazine). In 2006, Roche was ranked the No. 1 Company to Sell For (Selling Power), and one of AARP's Top Companies for Older Workers, and in 2005, Roche was named one of Fortune magazine's Best Companies to Work For in America.

Posted: November 2007

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