Roche Responds to Announcement of 'IDEAL' Hepatitis C Trial Results

NUTLEY, N.J., January 14, 2008 /PRNewswire/ -- Following an announcement from Schering-Plough, Roche today affirmed the value of PEGASYS(R) (peginterferon alfa-2a) in combination with ribavirin as the market-leading treatment for patients with hepatitis C, in the United States and globally. Despite clear biases in the design of the "IDEAL" study that potentially favored patients taking Peg-Intron(TM) (peginterferon alfa-2b) regimens - particularly the ribavirin dose reduction protocol - the study results have shown that patients treated with a PEGASYS regimen had a similar chance of being successfully treated for hepatitis C.

"I do not expect that the results of the IDEAL study will meaningfully impact clinical practice, except to inform physicians on the appropriate dosing of Peg-Intron and to reinforce the already widely-accepted view that optimizing ribavirin dosing throughout treatment is critical to achieving success and preventing treatment relapse in hepatitis C," said Douglas Dieterich, M.D., Professor of Medicine in the Division of Hepatology at Mt. Sinai School of Medicine in New York, New York.

In 2001, the U.S. Food and Drug Administration (FDA) required Schering- Plough to conduct a post approval commitment trial to determine if a lower dose of Peg-Intron (1.0 mcg/kg) was as effective as the approved dose of 1.5 mcg/kg, both in combination with identical ribavirin regimens. A third arm was added to the study in which patients received PEGASYS 180 mcg with a different ribavirin dosing schedule. This mismatch of ribavirin dosing introduces several potential biases into the study because experts agree that an optimized dose of ribavirin, with either pegylated interferon, is critical to achieving success in hepatitis C treatment. In particular, maintaining a full dose of ribavirin has shown an important ability to reduce relapse following the end of treatment.

"PEGASYS quickly became the market leader after its launch, based on robust clinical data and patient and physician preference. We are convinced that physicians and patients will continue to choose PEGASYS/ribavirin combination therapy based on positive experience and sound clinical evidence," said George Abercrombie, President and CEO, Hoffmann-La Roche. "Our current focus at Roche is on advancing the treatment of hepatitis C by optimizing doses and duration of PEGASYS/ribavirin in patients with unmet medical need, while developing new compounds that have the potential to offer a successful outcome to even more patients."

Roche believes that it is critical for patients and physicians to receive complete information to fully understand the results of "IDEAL," so that treatment decisions can be based on sound scientific data.

Please see below for additional information about the "IDEAL" trial, Roche and PEGASYS, including important safety information.

    "IDEAL" Trial Design Issues

     * Starting doses of ribavirin were different in the Peg-Intron and

       PEGASYS arms of the study

     * The design calls for a more drastic ribavirin dose reduction for side

       effect management in most patients in the PEGASYS arm compared to

       patients in the Peg-Intron arms; in some cases, ribavirin dose

       reductions for patients in the PEGASYS arm were three times greater

       than for patients in the Peg-Intron arms. This is important because a

       substantial number of patients being treated for hepatitis C require

       their ribavirin dose to be reduced to manage side effects, and this

       could have an impact on the efficacy of the regimen

     * The PEGASYS arm was not blinded, meaning that patients and physicians

       knew which treatment was being administered. Many comparative studies

       are blinded to ensure that bias does not compromise the results

     * Erythropoetin (EPO) is a medication that is often given to treat

       ribavirin-related anemia and help patients maintain a higher ribavirin

       dose. However, physicians could only prescribe EPO after the first dose

       ribavirin reduction in the "IDEAL" trial. Since patients in the Peg-

       Intron arms generally had smaller ribavirin dose reductions, this

       introduces another potential bias and means those Peg-Intron patients

       were potentially able to maintain a higher dose of ribavirin compared

       to PEGASYS patients


About PEGASYS

PEGASYS was launched by Roche in 2002 and quickly became the leading treatment for patients with hepatitis C. It is indicated in combination with COPEGUS (ribavirin) 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 (e.g., 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: January 2008

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