Hoffmann-La Roche Inc. 340 Kingsland Street

Nutley, New Jersey 07110-1199

Public Affairs Department

News Release

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

Liver Transplant Patients

Hepatitis C is the Leading Cause of Liver Transplantation in U.S.

Nutley, NJ (March 21, 2005): 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® (peginterferon alfa-2a)
and CopegusÒ

(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.”

- more -

Contacts: Pamela Van Houten

Roche

(973) 562-2231

pamela.vanhouten@...

David Freundel

Manning, Selvage & Lee

(212) 468-3982

david.freundel@...

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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 posttransplation,

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 pretransplant

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

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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

- more -

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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: www.roche.com and U.S.: www.roche.us).

###

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Facts About Pegasys (Peginterferon alfa-2a) in Combination with Copegus

Indication

§ 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) 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.

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§ 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.

2. Adverse Events

§ Alpha interferons, including Pegasys, may cause or aggravate fatal or
lifethreatening

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

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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

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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
www.pegasys.com,

or by calling 1-877-PEGASYS.

# # #






Sandra Tara Balduf (Ane)

Frontline Hepatitis Awareness

Support for patients and educational materials

http://frontline-hepatitis-awareness.com

1-866-Hep-GoGo 866-437-4646




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