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Roche Announces New Study to Evaluate Pegasys and Copegus to Treat Hepatitis C in Liver Transplant Patients

Posted on: Monday, 21 March 2005, 15:00 CST

NUTLEY, N.J., March 21 /PRNewswire/ -- Roche has initiated a new study to evaluate treatment strategies to reduce post-transplant recurrence of hepatitis C infection with the most prescribed hepatitis C treatment combination in the U.S., Pegasys(R) (peginterferon alfa-2a) and Copegus(R) (ribavirin, USP). In the United States, hepatitis C is the leading cause of liver transplantation.

The new study will compare prophylactic combination therapy with Pegasys and Copegus (to prevent the virus from attacking the transplanted liver) with the same combination therapy administered once hepatitis C infection recurs histologically in the transplanted liver.

"Hepatitis C is one of the greatest challenges we face in liver transplantation today," said Juan Carlos Lopez-Talavera, M.D., Ph.D., Senior Medical Director, Roche. "Approximately 30 percent of all Americans who receive liver transplants each year have chronic hepatitis C. We know that without treatment, hepatitis C almost always begins to attack the transplanted liver in patients with the disease."

Hepatitis C, a blood-borne infectious disease of the liver, is transmitted through body fluids, primarily blood or blood products, and by sharing needles. Hepatitis C chronically infects an estimated 2.7 million Americans and 170 million people worldwide.

"There are many questions to be answered such as how safe and effective is hepatitis C combination therapy for patients who have received a liver transplant, and when is treatment most effective. It is our hope that this study will help determine the best strategy for managing hepatitis C in patients who have received a liver transplant," said Michael Charlton, M.D., Associate Professor of Medicine and Director of Transplant Research, Mayo Clinic College of Medicine.

The study will enroll approximately 300 patients and include 28 trial sites throughout the United States. Patients in the study will be randomized into two arms between the 10th and 16th week post liver transplantation. Study participants who have not experienced liver damage post-transplantion, will receive 135mcg/week of Pegasys via subcutaneous injection for the first 4 weeks, which will then increase to 180mcg/week for the next 44 weeks. Patients will also receive between 400 mg/day to 1200 mg/day (escalated) of Copegus. Participants in the observation arm of the study will not receive treatment unless histological recurrence is demonstrated. These patients will then receive Pegasys and Copegus treatment with similar dosing as the prophylactic arm.

All patients must be over 18 years of age and have had a cadaveric liver transplantation due to hepatitis C between 10 to 16 weeks prior to initiation of treatment. Patients with a pre-transplant diagnosis of hepatocellular

carcinoma (HCC), or liver cancer, may be enrolled provided there is no evidence that the cancer has spread, tumor is solitary and less than 5cm or there are up to three tumors less than 3cm. Patients who received multiple organs, or who have hepatitis A or hepatitis B infection, human immunodeficiency virus (HIV), pre-existing severe depression or other psychiatric disease, significant cardiac disease, renal disease, seizure disorders, or severe retinopathy are excluded.

All patients will be evaluated at 24 months to determine if they have experienced hepatitis C recurrence measured by fibrosis stage 2 or greater and/or inflammation grade 3 or greater.

For more information about this trial and to locate a study site, patients can call 1-800-351-5537.

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. In addition, Pegasys is the only pegylated interferon approved by the FDA for use alone and in combination with Copegus for the treatment of chronic hepatitis C in patients coinfected with hepatitis C and HIV.

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).

1.1.1 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.

1.2 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 - 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.

* 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.

Roche

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

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

Source: PRNewswire

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