- Largest Prospective Study Demonstrates Treatment Success, and Highlights Potential Factors that Affect Health Outcomes, in Latino Population Suffering from Chronic Hepatitis C -

NUTLEY, N.J., Jan. 14 /PRNewswire/ -- Results from the LATINO study, the largest study conducted to-date in Latino patients with the hepatitis C virus (HCV), were published today in The New England Journal of Medicine (NEJM).(1) This Roche study demonstrated that HCV can be successfully treated among Latino patients, a patient population that is historically difficult to treat.(1,2,3,4) The study, "Peginterferon Alfa-2a and Ribavirin in Latino and Non-Latino Whites with Hepatitis C," was conducted to better understand how previously untreated Latino patients with HCV genotype 1, the most difficult-to-treat genotype, responded to treatment with PEGASYS(R) (peginterferon alfa-2a) plus COPEGUS(R) (ribavirin) as compared to non-Latino whites.(1)

"We know that the hepatitis C virus affects Latino patients differently than non-Latino patients, but there was little data available to support what we have seen clinically. The LATINO data are important because, for the first time, a large-scale study was conducted that focused on Latino patients, providing insight into this growing population," said Maribel Rodriguez-Torres, M.D., of the Fundacion de Investigacion de Diego in Puerto Rico. "We hope that this landmark LATINO study will be the beginning of more clinical trials with greater numbers of Latino patients, which will help address the unmet medical need of this population."

The data showed that Latino patients achieved sustained virological response (SVR) at a lower rate than non-Latino whites, and demonstrated that there were differences in predictors of SVR between the two patient populations.(1) The results of this study add to a growing body of evidence of differences in treatment responses among ethnic groups and underscore the need to optimize treatment strategies in order to improve the rate of SVR among Latino patients infected with HCV genotype 1.(1)

"As leaders in hepatology, we are proud to have conducted the largest prospective study of the Latino population with hepatitis C," said Dr. Lars Birgerson, Head of Global Medical Affairs, Roche. "We look forward to further investigating unmet medical needs and providing future treatment options, for Latinos and other hard-to-treat populations, through our clinical research program."

These findings point to an important public health issue, since Latinos, the fastest-growing minority population in the United States, have a higher prevalence of HCV(5) and more rapid fibrosis progression than non-Latino whites,(2) and a mortality rate of nearly twice that of non-Latino whites.(6) The predicted expansion of the number of Latinos in the United States suggests that the prevalence of HCV infection will increase. These factors are likely to contribute to the already increasing rates of morbidity and mortality among Latinos due to liver disease.

The LATINO study, a prospective, multicenter, open-label, nonrandomized trial, was designed to compare the efficacy of PEGASYS plus COPEGUS in 269 Latino whites and 300 non-Latino whites infected with HCV genotype 1 who had not been previously treated.(1) The primary endpoint of the study was SVR.(1) All patients, between the ages of 18 and 65, were treated with PEGASYS 180 mcg/wk plus COPEGUS 1,000 or 1,200 mg/day for 48 weeks.(1) Patients were then followed through 72 weeks.(1) Latinos were required to have two generations of Latino ancestry with Spanish as a primary language, and non-white Latinos were excluded.(1)

The results from LATINO showed that 34 percent (90/269) of the Latino patients achieved SVR when treated with PEGASYS plus COPEGUS.(1) In comparison, 49 percent (148/300) of patients in the non-Latino group achieved SVR, a difference of 16 percent, highlighting that Latino patients with HCV are more difficult to treat.(1) SVR was defined as undetectable HCV RNA 24 weeks after the end of treatment.(1) Combination therapy with PEGASYS plus COPEGUS was generally well tolerated, with similar rates of withdrawals between the groups for serious adverse events, with fatigue, fever and flu-like symptoms being the most common adverse events.(1)

These results contribute to a growing body of evidence that PEGASYS provides a successful outcome for many patients with HCV. PEGASYS has consistently demonstrated efficacy in a broad range of patient types, even those with poor prognostic factors, including African Americans and patients co-infected with HIV.(7,8,9,10,11) Two independent, investigator-initiated, single-center Italian studies with PEGASYS have shown reproducible efficacy in HCV patients with genotype 1 and 4 compared to peginterferon alfa-2b.(12,13) In genotypes 1 and 4 - the most difficult-to-treat patient group - 55 percent of patients taking PEGASYS achieved SVR, compared to 40 percent of patients in the peginterferon alfa-2b group.(12) Results of another study found significantly higher SVR rates in patients treated with PEGASYS and ribavirin compared to those treated with peginterferon alfa-2b and ribavirin (66 percent vs. 54 percent).(13) 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).(13)

As the current foundation of HCV treatment, PEGASYS is the pegylated interferon therapy of choice for most HCV antiviral agents in development. These collaborations position Roche as a leader in the next evolution of HCV treatment, and the LATINO study underscores Roche's role as a pioneer in the advancement of understanding HCV.

About Hepatitis C

HCV 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 HCV; 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 HCV-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 HCV 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 HCV in patients coinfected with HCV 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 HCV, with major studies initiated to advance treatment for HCV 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.

(1) Rodriguez-Torres M, et al. Peginterferon Alfa-2a and Ribavirin in Latino and Non-Latino Whites With Hepatitis C. N Engl J Med 2009;360:257-67.

(2) Rodriguez-Torres M. Latinos and Chronic Hepatitis C: A Singular Population. Clin Gastroenterol Hepatol 2008;6(5):484-90.

(3) Hepburn MJ, et al. Differences in Treatment Outcome for Hepatitis C Among Ethnic Groups. Am J Med 2004;117:163-8.

(4) Munoz H, et al. Response to Combination Therapy of Interferon Alfa-2b Plus Ribavirin in Hispanics With Chronic Hepatitis C. PR Health Sci J 2004;23:Suppl:61-7.

(5) Alter MJ, et al. The Prevalence of Hepatitis C Virus Infection in the United States, 1988 Through 1994. N Engl J Med 1999:556-562.

(6) Wise M, Bialek S, Finelli L, Bell BP, Sorvillo F. Changing Trends in Hepatitis C-Related Mortality in the United States, 1995-2004. Hepatology 2008;47:1128-35.

(7) Fried MW, et al. Peginterferon Alfa-2a Plus Ribavirin for Chronic Hepatitis C Virus Infection. N Engl J Med 2002; 347 (13):975-982.

(8) 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.

(9) 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.

(10) 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.

(11) 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.

(12) Ascione A, et al. Peginterferon Alpha-2a Plus Ribavirin Versus Peginterferon Alpha-2b Plus Ribavirin in Naive Patients with Chronic Hepatitis C Virus Infection: Results of a Prospective Randomized Trial. Presented at: 43rd Annual Meeting of the European Association for the Study of the Liver (EASL); April 23-27, 2008; Milan, Italy.

(13) Rumi M, et al. Randomized Study Comparing Peginterferon Alpha-2a Plus Ribavirin Versus Peginterferon Alpha-2b Plus Ribavirin in Naive Patients with Chronic Hepatitis C; Final Results of the Milan Safety Tolerability Study. Presented at: 59th Annual Meeting of the American Association for the Study of Liver Disease (AASLD); October 31-November 4, 2008; San Francisco, USA.

    Contact:  Linda Dyson
              Roche
              973-562-2231 (office)
              973-986-5973 (mobile)
              Linda.Dyson@roche.com

SOURCE Roche