Following an announcement from
Schering-Plough, Roche affirmed the value of PEGASYS(R)
(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(TM) (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 Douglas
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 George 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.
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: rocheusa or roche.us.
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