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New Study Shows that PEGASYS(R) Regimen Provides Higher Sustained

November 1, 2008
-- Higher Sustained Virological Response Rates Recognized as Marker of Treatment Success

SAN FRANCISCO, Calif., Nov. 1 /PRNewswire/ -- A new, independently-conducted study being presented at the 59th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) shows that PEGASYS(R) (peginterferon alfa-2a) treatment regimens result in higher sustained virological response (SVR) rates for hepatitis C patients as compared to regimens with another pegylated interferon.(1)

Comparing Today's Standard Treatment Regimens: The Milan Safety Tolerability Study

The Milan Safety Tolerability Study (MIST) randomly assigned 431 patients to receive PEGASYS or PegIntronTM, both in combination with ribavirin. In the PEGASYS group, the daily ribavirin dose for genotype 1 and 4 patients was 1000-1200 mg based on weight, while patients with genotype 2 or 3 received a fixed dose of ribavirin (800 mg). In the PegIntron group, ribavirin doses ranged from 800 mg to 1400 mg based on a patient's weight in all genotypes. The primary endpoint was to compare the safety and tolerability. The secondary endpoint was to compare efficacy.

Professor Colombo, Head of the 1st Division of Gastroenterology and A.M. Migliavacca Center for Liver Disease at the University of Milan, and colleagues will present the results of a study, which found significantly higher SVR rates in patients treated with PEGASYS/ribavirin as compared to those treated with peginterferon alfa-2b (PegIntron)/ribavirin (66 percent vs. 54 percent, p=0.02). The difference was sustained in patients with the most difficult to treat forms of the virus, those infected with genotypes 1 or 4 (48 percent vs. 32 percent, p=0.02). The two regimens showed a similar safety and tolerability profile, with similar rates of serious adverse events (2 percent in both arms) and drop outs for side effects (7 percent vs. 6 percent).

"Our study combines the rigor of a randomized, controlled trial with the general applicability of a 'real-world' study, since it included all patients at our clinic who initiated hepatitis C treatment and met basic eligibility criteria," said Professor Colombo. "The results from this study prove that treatment success rates in the real world can be comparable to those achieved in clinical trials. The study also demonstrates that PEGASYS regimens enable significantly more patients to achieve a SVR."

PEGASYS has demonstrated efficacy in a broad range of patient types, even those with poor prognostic factors.(2)(3)(4)(5)(6)

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), 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. 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

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(R) (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(R), 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 greater than or equal to 6) is observed. Ischemic and hemorrhagic cerebrovascular events have been observed in patients treated with interferon alfa-based therapies, including PEGASYS. Events occurred in patients with few or no reported risk factors for stroke, including patients less than 45 years of age. Because these are spontaneous reports, estimates of frequency cannot be made and causal relationship between interferon alfa-based therapies and these events is difficult to establish.

The most common adverse events reported for PEGASYS and COPEGUS combination therapy observed in clinical trials were fatigue/asthenia (65 percent), headache (43 percent), pyrexia (41 percent), myalgia (40 percent), irritability/anxiety/nervousness (33 percent), insomnia (30 percent), alopecia (28 percent), neutropenia (27 percent), nausea/vomiting (25 percent), rigors (25 percent), anorexia (24 percent), injection site reaction (23 percent), arthralgia (22 percent), depression (20 percent), pruritus (19 percent) and dermatitis (16 percent).

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. For additional information about the U.S. pharmaceuticals business, visit our website http://www.rocheusa.com/. Product and treatment information for U.S. healthcare professionals is available at www.RocheExchange.com.

All trademarks used or mentioned in this release are protected by law.

PegIntronTM is a trademark product of Schering Plough Corporation.

(1) Rumi M, Aghemo A, Prati G, et al. Randomized study comparing peginterferon-alfa-2a plus ribavirin and peginterferon-alfa-2b plus ribavirin in naive patients with chronic hepatitis C: final results of the Milan Safety Tolerability Study. Abstract presented at the American Association for the Study of Liver Disease; 31 October 2008; San Francisco, California, USA.

(2) Fried MW et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002; 347 (13): 975-982.

(3) Hadziyannis SJ et al. Peginterferon-2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med. 2004; 140(5):346-355.

(4) Conjeevaram HS et al. Peginterferon and ribavirin treatment in African American and Caucasian American patients with hepatitis C genotype 1. Gastroenterology. 2006; 131(2):470-477.

(5) Jeffers LJ et al. Peginterferon alfa-2a (40 kd) and ribavirin for black American patients with chronic HCV genotype 1. Hepatology. 2004;39(6):1702-1708.

(6) Rodriguez-Torres M et al. Virologic responses to peginterferon alfa-2a/ribavirin in treatment-naive Latino vs non-Latino Caucasian infected with HCV genotype 1: the Latino study. Presented at: 43rd Annual Meeting of the European Association for the Study of the Liver (EASL); April 23-27, 2008; Milan, Italy.

Source: Roche

CONTACT: Linda Dyson of Roche, mobile, +1-973-986-5973, Linda.Dyson@roche.com

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