Treatment with PEGASYS/COPEGUS Provides Hope for Hepatitis C Patients Whose Infection Did Not Initially Respond to Peg-Intron/Ribavirin
-- Response at 12 weeks is a powerful predictor of eventual
treatment success --
BOSTON, November 2, 2007 – Roche today announced final
results from the REPEAT study, which demonstrated that treatment
with once-weekly PEGASYS® (peginterferon alfa-2a) and daily
COPEGUS™ (ribavirin) for 72 weeks is a promising treatment
option for patients whose infection did not respond to previous
treatment with another pegylated interferon (Peg-Intron®,
peginterferon alfa-2b) and ribavirin. Further, the results showed
that response at 12 weeks was a powerful predictor of the eventual
outcome: the majority of patients with undetectable virus at 12
weeks went on to achieve a sustained virological response (SVR)
after 72 weeks of treatment, while few patients with detectable
virus at 12 weeks achieved SVR. These data were presented in an
oral session at the 58th Annual Meeting of the American Association
for the Study of Liver Diseases (AASLD), being held in Boston, Nov.
2-6.
“One of the greatest areas of need in hepatitis C today is to
find solutions for patients who have not seen treatment success
with an initial course of therapy. REPEAT is an important study
which adds significantly to our knowledge about how to manage these
patients, demonstrating that extending treatment with PEGASYS and
COPEGUS is a promising option,” said Donald Jensen, M.D.,
Professor of Medicine and Director of the Center for Liver
Diseases
at the University of Chicago Hospital in Chicago, and lead
investigator in REPEAT. “A significant finding from REPEAT is
confirmation of the reliability of using a patient’s response
at 12 weeks as a predictor of treatment success, even in patients
with cirrhosis. This means that patients who achieve undetectable
virus at 12 weeks can continue treatment with a good likelihood of
success. It also means that clinicians can confidently discontinue
treatment in patients who do not achieve an early
response.”
More About the REPEAT Study
Enrolling 950 patients from Europe, North America and Latin
America, REPEAT (REtreatment with PEgasys in pATients Not
Responding to Peg-Intron Therapy) was designed to explore whether
intensified treatment with a higher fixed-dose induction of PEGASYS
in combination with COPEGUS and/or longer treatment duration may
increase treatment success rates in patients who didn’t
respond to at least twelve weeks of Peg-Intron/ribavirin
combination therapy. Patients were randomized 2:1:1:2 to one of
four regimens:
• Patients in arms A (n=318) and B (n=158) received PEGASYS
360 mcg/week for 12 weeks, followed by 180 mcg/week for a further
60 or 36 weeks, respectively
• Patients in arms C (n=158) and D (n=316) received PEGASYS
180 mcg/week for 72 or 48 weeks, respectively
• All patients received COPEGUS (1,000/1,200 mg/day) in
combination with PEGASYS
Results showed:
• The primary endpoint was met: SVR, defined by undetectable
hepatitis C virus RNA in the blood six months after the end of
treatment, was significantly higher for arm A (16 percent) compared
to arm D (nine percent)
• A pooled analysis of the 72-week arms vs. the 48-week arms
showed that 72 weeks of treatment had the biggest impact on success
of treatment, with a doubling of SVR rate compared to 48 weeks (16
percent vs. eight percent). A pooled analysis of the induction dose
arms vs. standard dose arms showed that treatment with higher
fixed-dose induction for this difficult-to-treat patient population
did not provide significant additional benefit
• Response at 12 weeks was a strong predictor of successful
treatment
o Of patients whose virus was undetectable after 12 weeks of
therapy, 57 percent in the 72-week arms went on to achieve
treatment success (by comparison, among patients who still had
detectable virus after 12 weeks, only four percent achieved
treatment success)
o The proportion of patients with undetectable virus at 12 weeks
was 17 percent
“REPEAT exclusively enrolled patients who had not previously
responded to pegylated interferon combination therapy, in this case
Peg-Intron and ribavirin,” continued Dr. Jensen.
“These patients are more difficult-to-treat group than
relapsers and those who did not respond at all to treatment with
non-pegylated interferons, either alone or with ribavirin. For this
reason, results from REPEAT cannot be meaningfully compared to
results from trials with a large proportion of patients who were
relapsers or who did not respond to treatment with older
interferons.”
The incidence and types of adverse events and serious adverse
events were generally consistent across all the arms, and the
frequency of moderate to severe hematologic effects were broadly
similar across all arms. Discontinuations for adverse events and
lab abnormalities were higher for extended treatment. Patients with
cirrhosis had a somewhat higher incidence of adverse events,
premature withdrawals and dose modifications. (Please see below for
complete safety information about PEGASYS and COPEGUS.)
About Hepatitis C
Hepatitis C is a blood-borne infectious disease of the liver and a
leading cause of cirrhosis, liver cancer and the need for liver
transplants. According to the Centers for Disease Control and
Prevention (CDC), an estimated 4.1 million Americans (1.6 percent)
have been infected with hepatitis C; 3.2 million are chronically
infected. The number of new infections per year has declined from
an average of 240,000 in the 1980s to about 26,000 in 2004. CDC
estimates the number of hepatitis C-related deaths could increase
to 38,000 annually by the year 2010, surpassing annual HIV/AIDS
deaths.
About PEGASYS
PEGASYS, in combination with COPEGUS (ribavirin), are indicated 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 aggravatefatal 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 (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 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
1-800-593-2214. 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./a>
Posted: November 2007
