FDA Grants Priority Review to Market Leader Pegasys(R) With Copegus(R) for Treatment of Hepatitis C in HIV Patients

-- Signals Major Step Toward Satisfying Unmet Medical Need --



Oct 06, 2004, 01:00 ET from Roche

    NUTLEY, N.J., Oct. 6 /PRNewswire/ -- The U.S. Food and Drug Administration
 (FDA) has granted a six-month Priority Review Status to the supplemental new
 biologics license application (sBLA) for Roche's combination therapy of
 Pegasys(R) (peginterferon alfa-2a) in combination with Copegus(R) (ribavirin,
 USP) for the treatment of chronic hepatitis C in patients co-infected with
 HIV.  Roche submitted this file with the FDA in August 2004.
     Pegasys, the most prescribed hepatitis C medication in the U.S., is
 approved for use alone and in combination with Copegus for the treatment of
 adults with chronic hepatitis C.  Priority review designation was granted for
 the Pegasys and Copegus submission in co-infected patients because the
 indication would address an unmet medical need.
     "There are currently no approved treatments for the approximately 300,000
 people in the United States with HIV who are infected with hepatitis C," said
 Juan Carlos Lopez-Talavera, M.D., Ph.D., Senior Medical Director, Roche.
 "Roche invested in the research to pursue an indication for Pegasys
 combination therapy in co-infected patients because we recognized that the
 need is urgent.  Liver failure resulting from chronic hepatitis C is now one
 of the leading causes of death in people with HIV."
     HCV and HIV are the two most prevalent blood-borne infections in the
 United States, and HCV/HIV co-infection is increasingly recognized as a
 growing public health problem.  According to the Centers for Disease Control,
 hepatitis C has become a major cause of death for people with HIV.
 Almost four million Americans are believed to have chronic hepatitis C.
     The file submitted to the FDA includes results from APRICOT (AIDS Pegasys
 Ribavirin International Co-infection Trial), the largest study conducted to
 date evaluating chronic hepatitis C treatment in patients co-infected with HIV
 and HCV.  APRICOT is one of the six Pegasys studies published in The New
 England Journal of Medicine.  The results showed that 40 percent of patients
 treated with Pegasys and Copegus achieved a sustained virological response
 (SVR).  SVR refers to a patient's continued undetectable hepatitis C virus
 levels in the blood 24 weeks after finishing a course of treatment.
 
     About Pegasys
     Pegasys, a pegylated alpha interferon, and Copegus 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.
     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,
 patients with normal ALT levels, and patients who have failed to respond to
 previous therapy.
 
     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 and
 diagnostics.  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 Indication
     * Pegasys(R), a pegylated alpha interferon, alone or in combination with
 Copegus(R) (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
     * 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
     * The two combination therapy pivotal study findings:
     * Study 5, published in the March 2, 2004 Annals of Internal Medicine,
 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:
       * Genotype 1:  48 week duration with 1000 - 1200mg Copegus:         51
 percent
       * Genotype non-1:  24 week duration with 800mg Copegus:  82 percent
 
     * 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
     * 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).
     * 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).
     * 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).
     * 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.
     * 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%).
     * 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).
     * The complete package inserts for Pegasys and Copegus are available at
 http://www.pegasys.com , or by calling 1-877-PEGASYS.
 
 

SOURCE Roche
    NUTLEY, N.J., Oct. 6 /PRNewswire/ -- The U.S. Food and Drug Administration
 (FDA) has granted a six-month Priority Review Status to the supplemental new
 biologics license application (sBLA) for Roche's combination therapy of
 Pegasys(R) (peginterferon alfa-2a) in combination with Copegus(R) (ribavirin,
 USP) for the treatment of chronic hepatitis C in patients co-infected with
 HIV.  Roche submitted this file with the FDA in August 2004.
     Pegasys, the most prescribed hepatitis C medication in the U.S., is
 approved for use alone and in combination with Copegus for the treatment of
 adults with chronic hepatitis C.  Priority review designation was granted for
 the Pegasys and Copegus submission in co-infected patients because the
 indication would address an unmet medical need.
     "There are currently no approved treatments for the approximately 300,000
 people in the United States with HIV who are infected with hepatitis C," said
 Juan Carlos Lopez-Talavera, M.D., Ph.D., Senior Medical Director, Roche.
 "Roche invested in the research to pursue an indication for Pegasys
 combination therapy in co-infected patients because we recognized that the
 need is urgent.  Liver failure resulting from chronic hepatitis C is now one
 of the leading causes of death in people with HIV."
     HCV and HIV are the two most prevalent blood-borne infections in the
 United States, and HCV/HIV co-infection is increasingly recognized as a
 growing public health problem.  According to the Centers for Disease Control,
 hepatitis C has become a major cause of death for people with HIV.
 Almost four million Americans are believed to have chronic hepatitis C.
     The file submitted to the FDA includes results from APRICOT (AIDS Pegasys
 Ribavirin International Co-infection Trial), the largest study conducted to
 date evaluating chronic hepatitis C treatment in patients co-infected with HIV
 and HCV.  APRICOT is one of the six Pegasys studies published in The New
 England Journal of Medicine.  The results showed that 40 percent of patients
 treated with Pegasys and Copegus achieved a sustained virological response
 (SVR).  SVR refers to a patient's continued undetectable hepatitis C virus
 levels in the blood 24 weeks after finishing a course of treatment.
 
     About Pegasys
     Pegasys, a pegylated alpha interferon, and Copegus 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.
     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,
 patients with normal ALT levels, and patients who have failed to respond to
 previous therapy.
 
     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 and
 diagnostics.  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 Indication
     * Pegasys(R), a pegylated alpha interferon, alone or in combination with
 Copegus(R) (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
     * 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
     * The two combination therapy pivotal study findings:
     * Study 5, published in the March 2, 2004 Annals of Internal Medicine,
 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:
       * Genotype 1:  48 week duration with 1000 - 1200mg Copegus:         51
 percent
       * Genotype non-1:  24 week duration with 800mg Copegus:  82 percent
 
     * 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
     * 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).
     * 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).
     * 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).
     * 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.
     * 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%).
     * 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).
     * The complete package inserts for Pegasys and Copegus are available at
 http://www.pegasys.com , or by calling 1-877-PEGASYS.
 
 SOURCE  Roche