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New England Journal of Medicine Article Supports
PEGASYS(R) as a First-Line Therapy in Chronic Hepatitis B
NUTLEY, N.J., June
29 /PRNewswire/ -- According to a major study published in the June 30
edition of the New England Journal of Medicine, patients with the most
common form of hepatitis B in the United States who are treated with
PEGASYS(R) (peginterferon alfa-2a), the market-leading treatment for
hepatitis C, are more likely to achieve a sustained response than
those treated with lamivudine, the current standard of care. The
results indicate that PEGASYS offers a unique therapeutic option for
patients with chronic hepatitis B, and unlike oral treatment options,
offers patients a defined period of therapy.
In the Phase III study, conducted by Roche,
patients treated with PEGASYS displayed improvement in response rates
vs. lamivudine for both HBeAg, an antigen correlating with early and
active hepatitis B infection, and HBsAg, an antigen that elevates
before the onset of clinical symptoms. The addition of
lamivudine to PEGASYS did not improve the response rates at the end of
24-week follow-up.
"Treatment success in this study is measured
by HBeAg seroconversion, and these results demonstrate that more
patients achieved seroconversion when treated with PEGASYS than with
lamivudine," said study investigator, Dr. Michael Fried of The
University of North Carolina at Chapel Hill. "This is promising
news for the 1.25 million people in the United States who are
currently infected with hepatitis B."
Conclusions regarding comparative efficacy of
PEGASYS and lamivudine treatment based upon the end of follow-up
results are limited by the different mechanisms of action of the two
compounds. Most treatment effects of lamivudine are unlikely to
persist 24 weeks after therapy is withdrawn.
PEGASYS was approved in May 2005 for the treatment
of hepatitis B and is the first and only pegylated interferon
FDA-approved for treatment of both variations of the virus -- HBeAg-positive
and HBeAg-negative chronic hepatitis B. PEGASYS has a dual mode
of action: it slows replication of the hepatitis B virus and boosts
the immune system.
"Good therapeutic options are what people
affected by hepatitis B need. This appears to be another important
step forward," said Timothy M. Block, PhD, president of the
Hepatitis B Foundation. "I commend Roche for pursuing this
work and development."
Hepatitis B can lead to cirrhosis, hepatocellular
carcinoma (liver cancer), and death. It is estimated that
hepatitis B can cause more than 5,000 deaths in the United States each
year.
These results and conclusions confirm those from
another phase III Roche study of PEGASYS in patients with chronic
hepatitis B, which were also published in the New England Journal of
Medicine (NEJM) in 2004. That study showed PEGASYS was more effective
in achieving lasting remission than lamivudine in patients with a more
difficult-to-treat form of the disease (HBeAg negative).(i) The
results of this study also support PEGASYS as a first-line therapy for
HBeAg-negative chronic hepatitis B who have evidence of compensated
liver disease, evidence of viral replication and liver inflammation.
Key Study Facts
The Phase III study included 814 patients with
HBeAg-positive chronic hepatitis B and evidence of compensated liver
disease, evidence of viral replication and liver inflammation.
Patients were treated with either PEGASYS monotherapy plus oral
placebo, PEGASYS plus lamivudine, or lamiduvine alone for 48 weeks.
Patients were followed for an additional 24 weeks post-treatment.
The results of the study at the end of follow-up showed:
-- 32 percent of patients treated with
PEGASYS achieved HBeAg
seroconversion, compared with 19 percent of those treated with
lamivudine. PEGASYS and lamivudine combination therapy did not
improve the treatment outcome (27 percent of those on this combination
achieved HBeAg seroconversion). -- HBsAg
seroconversion was reported in 16 patients treated with PEGASYS
(with or without lamivudine) and in none of the patients treated with
lamivudine alone. "HBsAg loss or seroconversion after
therapy is considered
the ultimate therapeutic goal of anti-HBV therapy, since it
is associated with positive long-term clinical outcomes," the
authors note.
-- Conclusions regarding comparative efficacy of PEGASYS and
lamivudine treatment
based upon the end of follow-up results are limited by the
different mechanisms of action of the two compounds. Most
treatment effects of
lamivudine are unlikely to persist 24 weeks after therapy
is withdrawn. -- The most common adverse
events in the study included pyrexia (fever),
fatigue, headache, myalgia, alopecia and anorexia, all known to occur
with interferon alfa therapy.
PEGASYS was approved in 2002 by the FDA for use
alone and in combination with Copegus(R) (ribavirin, USP) for the
treatment of adults with chronic hepatitis C. In February 2005,
PEGASYS became the first and only FDA-approved therapy alone and in
combination with Copegus for the treatment of chronic hepatitis C in
patients co-infected with hepatitis C and clinically stable HIV.
This latest publication takes the total number of
PEGASYS publications in the NEJM to seven, the highest number of NEJM
publications for any pegylated interferon.
About Chronic Hepatitis B
In the U.S., the most common modes of transmission
of the hepatitis B virus are through sexual and blood-to-blood
contact, although the disease can also be transmitted from pregnant
women to their infants.
The number of new infections in the U.S. has
decreased in recent years, in part due to the introduction of the
hepatitis B vaccine in 1982. Almost all (90-95 percent) adults
who contract hepatitis B clear the virus from their systems within a
few months and develop immunity. The remainder of the infections
become chronic, which is when the virus stays in the blood, infecting
liver cells and possibly damaging them.
About PEGASYS for Hepatitis C
PEGASYS, a pegylated alpha interferon, and Copegus
are indicated 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 include patients with compensated liver
disease and patients with histological evidence of cirrhosis.
PEGASYS is dosed at 180mcg as a subcutaneous
injection taken once a week. Copegus is administered orally at doses
of 800-1200 mg daily.
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.
Please see attached additional information about
PEGASYS indication and safety.
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
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) and patients
with HIV disease that is clinically stable (eg, antiretroviral therapy
not required or receiving stable antiretroviral therapy).
PEGASYS is indicated for the treatment of adult
patients with HBeAg positive and HBeAg negative chronic hepatitis B
who have compensated liver disease and evidence of viral replication
and liver inflammation.
Alpha interferons, including PEGASYSR (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 COPEGUSR,
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 PLANNED 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. Cirrhotic CHC patients
coinfected with HIV receiving highly active antiretroviral therapy (HAART)
and interferon alfa-2a with or without ribavirin appear to be at
increased risk for the development of hepatic decompensation compared
to patients not receiving HAART. 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.
Exacerbations of hepatitis during hepatitis B
therapy are not uncommon and are characterized by transient and
potentially severe increases in serum ALT. Patients experiencing ALT
flares should receive more frequent monitoring of liver function.
PEGASYS dose reduction should be considered in patients experiencing
transaminase flares. If ALT increases are progressive despite
reduction of PEGASYS dose or are accompanied by increased bilirubin or
evidence of hepatitic decompensation, PEGASYS should be immediately
discontinued.
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%). The adverse
event profile of hepatitis B patients treated with PEGASYS was
generally similar to that shown for hepatitis C patients treated with
PEGASYS monotherapy except for exacerbations of hepatitis.
Serious adverse events included neuropsychiatric
disorders (suicidal ideation and suicide attempt), serious and severe
bacterial infections (sepsis), 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 thrombotic
thrombocytopenic purpura, psoriasis and lupus), 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).
(i) Marcellin P, Lau GK, Bonino F, et al. N Engl J
Med 2004;351:1206-17.
SOURCE Roche
06/29/2005 16:07 ET
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