Roche responds to announcement of 'IDEAL' hepatitis C trial results

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Roche responds to announcement of 'IDEAL' hepatitis C trial results

NUTLEY, N.J., Jan. 14 /PRNewswire/ -- Following an announcement from

Schering-Plough, Roche today affirmed the value of PEGASYS®

(peginterferon alfa-2a) in combination with ribavirin as the market-

leading treatment for patients with hepatitis C, in the United States

and globally. Despite clear biases in the design of the " IDEAL " study

that potentially favored patients taking Peg-Intron

(peginterferon alfa-2b) regimens - particularly the ribavirin dose

reduction protocol - the study results have shown that patients

treated with a PEGASYS regimen had a similar chance of being

successfully treated for hepatitis C.

" I do not expect that the results of the IDEAL study will

meaningfully impact clinical practice, except to inform physicians on

the appropriate dosing of Peg-Intron and to reinforce the already

widely-accepted view that optimizing ribavirin dosing throughout

treatment is critical to achieving success and preventing treatment

relapse in hepatitis C, " said Dieterich, M.D., Professor of

Medicine in the Division of Hepatology at Mt. Sinai School of

Medicine in New York, New York.

In 2001, the U.S. Food and Drug Administration (FDA) required

Schering- Plough to conduct a post approval commitment trial to

determine if a lower dose of Peg-Intron (1.0 mcg/kg) was as effective

as the approved dose of 1.5 mcg/kg, both in combination with

identical ribavirin regimens. A third arm was added to the study in

which patients received PEGASYS 180 mcg with a different ribavirin

dosing schedule. This mismatch of ribavirin dosing introduces several

potential biases into the study because experts agree that an

optimized dose of ribavirin, with either pegylated interferon, is

critical to achieving success in hepatitis C treatment. In

particular, maintaining a full dose of ribavirin has shown an

important ability to reduce relapse following the end of treatment.

" PEGASYS quickly became the market leader after its launch, based on

robust clinical data and patient and physician preference. We are

convinced that physicians and patients will continue to choose

PEGASYS/ribavirin combination therapy based on positive experience

and sound clinical evidence, " said Abercrombie, President and

CEO, Hoffmann-La Roche. " Our current focus at Roche is on advancing

the treatment of hepatitis C by optimizing doses and duration of

PEGASYS/ribavirin in patients with unmet medical need, while

developing new compounds that have the potential to offer a

successful outcome to even more patients. "

Roche believes that it is critical for patients and physicians to

receive complete information to fully understand the results

of " IDEAL, " so that treatment decisions can be based on sound

scientific data.

Please see below for additional information about the " IDEAL " trial,

Roche and PEGASYS, including important safety information.

" IDEAL " Trial Design Issues

* Starting doses of ribavirin were different in the Peg-Intron

and

PEGASYS arms of the study

* The design calls for a more drastic ribavirin dose reduction

for side

effect management in most patients in the PEGASYS arm compared

to

patients in the Peg-Intron arms; in some cases, ribavirin dose

reductions for patients in the PEGASYS arm were three times

greater

than for patients in the Peg-Intron arms. This is important

because a

substantial number of patients being treated for hepatitis C

require

their ribavirin dose to be reduced to manage side effects, and

this

could have an impact on the efficacy of the regimen

* The PEGASYS arm was not blinded, meaning that patients and

physicians

knew which treatment was being administered. Many comparative

studies

are blinded to ensure that bias does not compromise the results

* Erythropoetin (EPO) is a medication that is often given to

treat

ribavirin-related anemia and help patients maintain a higher

ribavirin

dose. However, physicians could only prescribe EPO after the

first dose

ribavirin reduction in the " IDEAL " trial. Since patients in

the Peg-

Intron arms generally had smaller ribavirin dose reductions,

this

introduces another potential bias and means those Peg-Intron

patients

were potentially able to maintain a higher dose of ribavirin

compared

to PEGASYS patients

About PEGASYS

PEGASYS was launched by Roche in 2002 and quickly became the leading

treatment for patients with hepatitis C. It is indicated in

combination with COPEGUS (ribavirin) for the treatment of adults with

chronic hepatitis C 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 hepatitis C in

patients coinfected with hepatitis C 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

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, and

patients who have failed to respond to previous therapy.

Important Safety Information about PEGASYS

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 (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, 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 (e.g.,

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-.

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 .6) is observed.

The most common adverse events reported for PEGASYS and COPEGUS

combination therapy observed in clinical trials 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 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. An

employer of choice, in 2007 Roche was named Top Company of the Year

by Med Ad News and one of the Top 20 Employers (Science magazine). In

2006, Roche was ranked the No. 1 Company to Sell For (Selling Power),

and one of AARP's Top Companies for Older Workers, and in 2005, Roche

was named one of Fortune magazine's Best Companies to Work For in

America. For additional information about the U.S. pharmaceuticals

business, visit our websites: http://www.rocheusa.com

[http://www.rocheusa.com] or www.roche.us [http://www.roche.us].

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