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FDA Approves Pegasys and Copegus As Only Hepatitis C Treatment for HIV Patients

Posted on: Friday, 25 February 2005, 18:00 CST

NUTLEY, N.J., Feb. 25 /PRNewswire/ -- Roche announced today that the U.S. Food and Drug Administration (FDA) has approved Pegasys(R) (peginterferon alfa-2a) and Copegus(R) (ribavirin, USP) for the treatment of chronic hepatitis C in patients coinfected with hepatitis C and HIV. Pegasys combination therapy is the first and only regimen FDA-approved for hepatitis C treatment in patients with HIV.

Pegasys, the most prescribed hepatitis C medication in the U.S., was approved in 2002 by the FDA for use alone and in combination with Copegus for the treatment of adults with chronic hepatitis C.

"For the first time, the 300,000 Americans who are coinfected with hepatitis C and HIV have an FDA-approved hepatitis C treatment option. This is a very important advance for the HIV community," said Jeffery Smith, Director, Clinical Research, American Foundation for AIDS Research (amfAR). "Hepatitis C has become one of the leading killers of people with HIV because advances in HIV treatment are helping patients live longer and because hepatitis C progresses much more quickly to liver failure in people with HIV."

Hepatitis C and HIV are the two most prevalent blood-borne infections in the United States. It is estimated that approximately 30 percent of Americans with HIV are also coinfected with the hepatitis C virus. Research has shown that hepatitis C is more resistant to treatment in people with HIV. Recent guidelines by the National Institutes of Health and Centers for Disease Control and Prevention recommend that people with HIV be screened for hepatitis C and that all patients with chronic hepatitis C, including those with HIV, be considered for treatment.

"The risks and benefits of medications can be very different for people with HIV, and research has suggested that this is true for hepatitis C therapies as well," said Douglas Dieterich, MD, Professor of Medicine, Mount Sinai School of Medicine, New York City. "Studies have shown that hepatitis C and HIV coinfected patients treated with Pegasys combination therapy had response rates that were three times higher than those treated with conventional interferon combination therapy."

"Making decisions based on evidence is particularly important for HIV patients given the unique and complex medical challenges that they face," said Salvatore Badalamenti, MD, Medical Director, Roche. "The safety and efficacy results from the APRICOT study and in our label can only be applied to Pegasys combination therapy."

Pegasys is the only pegylated interferon supported by published studies including U.S. patients for the treatment of hepatitis C in hepatitis C and HIV coinfected patients.

Pivotal Study

The FDA approval of Pegasys combination therapy for the treatment of HCV/HIV coinfected patients is based on results from APRICOT (AIDS Pegasys Ribavirin International Coinfection Trial), the largest-ever study to date evaluating chronic hepatitis C treatment in patients coinfected with hepatitis C and HIV. The results showed that 40 percent of patients treated with Pegasys and Copegus achieved a sustained virological response. Sustained virological response refers to a patient's continued undetectable hepatitis C levels in the blood 24 weeks after finishing a course of treatment.

The randomized, partially blinded international trial enrolled a total of 860 HCV/HIV coinfected patients in 19 countries, including the United States. All patients were HCV positive, had compensated liver disease, a CD4+ count greater than 100 cells/mL, and stable HIV disease, with or without antiretroviral therapy. Patients were randomized to 48 weeks of treatment with interferon alfa 2a 3MIU three times a week plus 800 mg/day of ribavirin, 180 mcg of Pegasys once weekly plus placebo, or 180 mcg of Pegasys once weekly with 800 mg/day of Copegus. Sustained virological response (SVR) was assessed at the end of 24 weeks of treatment-free follow up (week 72).

The adverse event profile of coinfected patients treated with Pegasys and Copegus was generally similar to that shown for monoinfected patients. Events occurring more frequently in coinfected patients were neutropenia (40%), anemia (14%), thrombocytopenia (8%), weight decrease (16%) and mood alteration (9%).

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.

The FDA is currently reviewing an indication for Pegasys for the treatment of chronic hepatitis B.

Pegasys is dosed at 180 mcg as a subcutaneous injection taken once a week. Copegus is available as a 200 mg 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 coinfected with hepatitis C and HIV, African Americans, patients with cirrhosis, patients with normal ALT levels, and patients who have failed to respond to previous therapy.

Data from six Pegasys studies, including APRICOT, have been published in The New England Journal of Medicine.

About Roche -- More Than a Century in the U.S. and the World

Founded in 1896 and headquartered in Basel, Switzerland, Roche is one of the world's leading innovation-driven healthcare groups. Its core businesses are pharmaceuticals and diagnostics. Roche is one of the world's leaders in diagnostics, the leading supplier of pharmaceuticals for cancer, as well as a leader in virology and transplantation. As a supplier of products and services for the prevention, diagnosis and treatment of disease, the Group contributes on many fronts to improve people's health and quality of life. Roche employs roughly 65,000 people in 150 countries, including approximately 15,000 in the United States.

Roche's U.S. operations celebrate their American Centennial in 2005. In another milestone this year, Roche was named in January to Fortune magazine's list of Best Companies to Work for in America. One of an increasingly rare breed of major healthcare companies that still bear their original name, Roche

today has more than a dozen U.S. sites located in California, Colorado, Indiana, New Jersey and South Carolina, as well as in Puerto Rico. Roche has alliances and research and development agreements with numerous partners, including majority ownership interests in Genentech and Chugai. Roche's Pharmaceuticals Division offers a portfolio of leading medicines in therapeutic areas including cancer, HIV/AIDS, hepatitis C, transplantation, dermatology and influenza. Roche's Diagnostics Division supplies a wide array of innovative testing products and services to researchers, physicians, patients, hospitals and laboratories world-wide. For further information, please visit our worldwide and U.S. websites (Global: http://www.roche.com/ and U.S.: http://www.roche.us/ ).

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) and

patients with HIV disease that is clinically stable (e.g.

antiretroviral therapy not required or receiving stable antiretroviral

therapy).

Dosing and Administration

* Pegasys, a premixed solution, is dosed at 180 mcg as a subcutaneous

injection once a week. Copegus, available as a 200 mg tablet, is

administered at 800 to 1200 mg taken twice daily as a split dose. The

two products are sold separately.

Combination Therapy Clinical Studies

* The two combination therapy pivotal study findings for patients without

HIV:

* 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 - 1200 mg Copegus: 51

percent

* Genotype non-1: 24 week duration with 800 mg 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.

* Combination therapy pivotal study findings for patients with HIV:

* Study 6, published in the July 29, 2004 New England Journal of

Medicine, including 868 HIV patients receiving medication, showed

that Pegasys and Copegus combination therapy is a more effective

treatment for chronic hepatitis C in patients with HIV than Pegasys

monotherapy and more effective than interferon alfa-2a and ribavirin.

The sustained virological response rate in the Pegasys and Copegus

treated patients was 40 percent compared to 11 percent in patients

treated with interferon alfa-2a and ribavirin and 20 percent in

patients treated with Pegasys monotherapy.

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 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 worsening of cardiac disease. Ribavirin is

genotoxic, 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 hepatitic

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 hepatitis decompensation with Child-Pugh

score greater than or equal to 6 in cirrhotic chronic hepatitis C

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 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.

Healthcare providers and patients are strongly encouraged to

immediately report any pregnancy in a patient or partner of a patient

during treatment or during six months after treatment cessation to the

Ribavirin Pregnancy Registry at 1-800-593-2214.

* Chronic hepatitis C patients with cirrhosis are at risk of hepatitic

decompensation and death when treated with alpha interferons, including

Pegasys and Copegus. Cirrhotic chronic hepatitis C patients coinfected

with HIV receiving highly active antiretroviral therapy (HAART) appear

to be at increased risk for the development of hepatitic decompensation

compared to monoinfected patients. 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.

* 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%). The adverse event profile of

coinfected patients treated with Pegasys and Copegus was generally

similar to that shown for monoinfected patients. Events occurring more

frequently in coinfected patients were neutropenia (40%), anemia (14%)

thrombocytopenia (8%) weight decrease (16%) and mood alteration (9%).

* 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.

Web sites: http://www.roche.us http://www.pegasys.com

Roche

CONTACT: Pamela Van Houten of Roche, +1-973-562-2231,pamela.vanhouten@roche.com; Dave Freunde of Manning, Selvage & Lee,+1-212-468-3982, david.freundel@mslpr.com, for Roche

Source: PRNewswire

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