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Newly Published Study Investigates Pegasys and Copegus (ribavirin) for the Treatment of Chronic Hepatitis C In Black Americans
  This is a press release from Roche and forwarded to you for your information.
Authors state: "To date, this is the highest response rate to treatment observed in a black population"
New York, NY (May 25, 2004) -- A study published in the June issue of Hepatology showed that 26 percent of black Americans with chronic hepatitis C treated with the most prescribed hepatitis C therapy in the U.S., a combination of Pegasys" (peginterferon alfa-2a), a pegylated interferon, and Copegus" (ribavirin, USP), an anti-viral medication, achieved a sustained virological response (SVR).
Sustained virological response refers to a patient's continued undetectable serum hepatitis C RNA levels 24 weeks after finishing a course of treatment.
The primary objective of the study was to investigate the efficacy, safety and tolerability of Pegasys combination therapy in non-Hispanic black Americans with genotype 1 hepatitis C virus (HCV), the strain of the virus that is most difficult to treat. In the article, the authors of the study state: "In summary, we have shown that 48 weeks of therapy with peginterferon alfa-2a and ribavirin results in an SVR in 26 percent of blacks chronically infected with HCV genotype 1. To date, this is the highest response rate to treatment observed in a black population." In black patients who completed 48 weeks of treatment, 32 percent achieved an SVR.
"Historically, black Americans infected with hepatitis C have been underrepresented in clinical trials," said Lennox Jeffers, MD, professor of medicine at the University of Miami School of Medicine and chief of Hepatology at the Miami VA Medical Center. "These results are very encouraging and have already led to a large National Institutes of Health (NIH) study involving 400 patients in eight centers throughout the United States to examine viral hepatitis C resistance in the black American population."
Hepatitis C is a blood-borne virus that chronically infects an estimated 2.7 million Americans. It can cause progressive liver injury and lead to fibrosis and eventually cirrhosis. Black Americans have the highest prevalence rates for hepatitis C among all racial and ethnic groups in the U.S. and hepatitis C treatment has historically been less effective in this population.
"The results of this study provide promising information for black Americans infected with hepatitis C," said Charles Howell, MD, associate professor in the Department of Medicine and director of Hepatology Research at the University of Maryland School of Medicine, and one of the lead investigators in the study. "Until now, the efficacy of peginterferon plus ribavirin for hepatitis C treatment in black Americans was unclear. This new data establishes the efficacy and safety of peginterferon alfa-2a (Pegasys) and ribavirin for African Americans infected with genotype 1, the most common variant of hepatitis C in the United States."
Study Design
The open-label noncomparative study was conducted at eleven sites in the United States and included 78 black patients and 28 white patients.
All patients were interferon-naïve with chronic hepatitis C genotype 1 and elevated ALT levels. Patients received 180 mcg subcutaneously of Pegasys, once weekly, along with either 1000 or 1200 mg/day of Copegus, depending on their weight, for 48 weeks, with 24 weeks of treatment-free follow-up. Early virological response (EVR) was assessed at 12 weeks of therapy and SVR at week 72.
This trial included a relatively small cohort of patients receiving treatment. Studies with larger patient populations are currently underway to confirm the findings from this study.
The SVR rate in white patients in the study was 39 percent, with a confidence interval of 21 to 57 percent. Conclusions should not be drawn in the white patient population because of the small number (n=28) in the study. In previous studies, more than half of patients with genotype 1 hepatitis C achieved a sustained virological response after 48 weeks of treatment with Pegasys combination therapy.
Histological Response
Paired liver biopsies were obtained from 53 of the black patients and 16 of the white patients. In these patients, more than 90 percent in both groups showed either improvement or stabilization of fibrosis (scar tissue in the liver). Improvements in fibrosis score occurred in 25 percent of all patients (13 of 53 patients).
Adverse Events
Adverse events were similar to those seen in Pegasys and Copegus registration trials. Incidence rates for AEs among the white patient and black patient groups included: fatigue (71 percent vs. 60 percent), headache (82 percent vs. 54 percent), rigors (35 percent vs. 32 percent), insomnia (50 percent vs. 27 percent), rash (26 percent vs. 18 percent), and nausea (54 percent vs. 23 percent). Five percent of black patients and fourteen percent of white patients withdrew prematurely due to adverse events or laboratory abnormalities. Black patients had lower baseline absolute neutrophil counts compared to white patients. Dose modifications of Pegasys (withheld or reduced) occurred among 46 percent of black patients and 29 percent of white patients; the most common cause was neutropenia (37 percent among black patients and 18 percent among white patients).
About Pegasys
Pegasys, a pegylated alpha interferon, and Copegus, an oral antiviral, were approved by the FDA in December 2002 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.
About Roche
Hoffmann-La Roche Inc. (Roche), based in Nutley, N.J., is the U.S. prescription drug unit of the Roche Group, a leading research-based health care enterprise that ranks among the world's leaders in pharmaceuticals, diagnostics and vitamins. Roche discovers, develops, manufactures and markets numerous important prescription drugs that enhance people's health, well-being and quality of life. Among the company's areas of therapeutic interest are: dermatology; genitourinary disease; infectious diseases, including influenza; inflammation, including arthritis and osteoporosis; metabolic diseases, including obesity and diabetes; neurology; oncology; transplantation; vascular diseases; and virology, including HIV/AIDS and hepatitis C.For more information on the Roche pharmaceuticals business in the United States, visit the company's web site at: http://www.rocheusa.com
Facts About Pegasys (Peginterferon alfa-2a) in Combination with Copegus
ß Pegasys, a pegylated alpha interferon, alone or in combination with Copegus® (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
ß 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
ß The two combination therapy pivotal study findings:
ß 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:
ß Genotype 1: 48 week duration with 1000 -- 1200mg Copegus: 51 percent
ß Genotype non-1: 24 week duration with 800mg Copegus: 82 percent
ß 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.
Adverse Events
ß 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).
ß 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).
ß 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).
ß 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.
ß 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%).
ß 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).
ß The complete package inserts for Pegasys and Copegus are available at www.pegasys.com, or by calling 1-877-PEGASYS.
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