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FDA
Approves Pegasys as the First and Only Pegylated Interferon for the Treatment
of Chronic Hepatitis B  In
a widely anticipated action, the US Food and Drug Administration (FDA) has approved
peginterferon alfa-2a (Pegasys)
for the treatment of chronic
hepatitis B (CHB). Pegasys is already FDA-approved for the treatment of chronic
hepatitis C infection (CHC).
The
FDA action makes Pegasys the first and only pegylated interferon approved for
the treatment of CHB, including for individuals who are hepatitis
B “e” antigen positive (HBeAg-positive) and hepatitis
B “e” antigen-negative (HBeAg-negative). Following
are excerpts from the approval announcement by Roche Pharmaceuticals (Roche): “Chronic
hepatitis B infection is a serious disease that causes more than 5,000 deaths
in the United
States each year,” said Salvatore Badalamenti, M.D., Medical Director, Roche.
“Pegasys now
offers hepatitis B patients a treatment option that is taken for a fixed duration
of 48 weeks with
the goal of providing a lasting response after treatment is completed.” The
US Centers for Disease Control and Prevention estimates that 1.25 million people
in the United States are chronically infected with hepatitis B. Chronic hepatitis
B can lead to cirrhosis,
hepatocellular carcinoma
and death. “This
approval provides another important option for the treatment of hepatitis B,”
said Frederick
G. Thompson, President and CEO of The American Liver Foundation. “We commend Roche
for its extensive research and commitment to treating people with chronic liver
diseases.” Pegasys
has a dual mode of action; it slows replication of the hepatitis B virus and boosts
the
immune system. Pivotal
Studies The
two large-scale multinational phase III trials, in more than 1,500 patients with
both the
HBeAg-positive and HBeAg-negative variations of chronic hepatitis B, demonstrated
that 24 weeks
after a defined 48 week period of therapy, more patients achieved a sustained
response with
Pegasys than with lamivudine
(Epivir-HBV). These studies demonstrated
that the addition of lamivudine to Pegasys did not improve response rates over
Pegasys alone. Specifically,
hepatitis B patients treated with Pegasys had higher rates of:
-
HBV seroconversion in HBeAg positive patients (32% Pegasys vs. 19% lamivudine)
-
HBV DNA response (32% Pegasys vs. 22% lamivudine in HBeAg positive patients and
43% Pegasys vs. 29% lamivudine in HBeAg negative patients)
-
ALT normalization in HBeAg negative patients (59% Pegasys vs. 44% lamivudine)
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, according to Roche.
Recent
results from a long-term follow up study presented at the 40th annual
meeting of the European
Association for the Study of the Liver (40th EASL, April 13-17) indicate
that patients with HBeAg-negative chronic hepatitis B who responded to treatment
with Pegasys maintained the benefit for at least a year after treatment. The
phase III study
results in individuals with HBeAg-negative chronic hepatitis B
were published in the September 2004 in the New England Journal of Medicine.
The results of the phase III study in patients with HBeAg-positive chronic hepatitis
B were presented at the 40th
EASL. Lead
investigators of both studies stated that the results of the trials warrant Pegasys
becoming
a first-line treatment for HBeAg-positive and HBeAg-negative chronic hepatitis
B. Roche
was granted approval by the EU Commission in late February 2005 to market Pegasys
for the treatment of chronic hepatitis B. About
Chronic Hepatitis B In
the US 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 US 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. Facts
about Pegasys (Peginterferon Alfa-2a) 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 alfa. 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. Adverse
Effects Alpha
interferons, including Pegasys, 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 for Pegasys)  . 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).
Recent HIV and Hepatitis.com Articles on Pegasys for
Chronic Hepatitis B:
Peginterferon
Alfa-2a (Pegasys) Produces a Sustained Response in HBeAg-negative HBV Patients
One Year after the End of Treatment - 4/25/05 Factors
Predicting Response to Pegylated Interferon in HBeAg Positive Chronic Hepatitis
B - 4/22/05 Peginterferon
Alfa-2a (Pegasys) Versus Peginterferon Alfa-2a Plus Lamivudine Versus Lamivudine
Alone In HBeAg Positive Chronic HBV - 4/18/05
Peginterferon
Alfa-2a Alone, Lamivudine Alone, and the Two in Combination in Patients with
HBeAg-Negative Chronic Hepatitis B - 9/17/04
Other
HIV and Hepatitis.com Articles on Pegasys for Chronic Hepatitis B: Factors
Predicting Response to Pegylated Interferon in HBeAg Positive Chronic Hepatitis
B - 4/22/05
Peginterferon
Alfa Is Effective in Almost One-third of Patients Who Failed Previous Treatment
with Standard Interferon or Lamivudine - 11/17/04
Patients
with Chronic Hepatitis B Have Better Safety and Quality of Life When Treated with
Peginterferon Alfa-2a (Pegasys) Monotherapy Compared to Those with Chronic
Hepatitis C 11/01/04
Current
Treatments for Hepatitis B: An Overview - 10/25/04
Peginterferon
Alfa-2a Alone, Lamivudine Alone, and the Two in Combination in Patients with
HBeAg-Negative Chronic Hepatitis B 09/17/04
Pegasys
Monotherapy Produces Significantly Higher Sustained Response Rates (SVR) Compared
to Epivir-HBV 04/30/04
A New
Bio-Mathematical Model Describes the Dynamics of HBV-DNA and Infected Hepatocytes
in Patients Treated with Peginterferon alfa-2a Monotherapy, Lamivudine or Peginterferon
Alfa-2a (Pegasys) Plus Lamivudine (Epivir-HBV) 04/21/04
Peginterferon
Alfa-2a (Pegasys) Monotherapy is More Effective Than Lamivudine (Epivir-HBV)
Monotherapy for HBeAg-negative Chronic HBV Patients 04/21/04
Pegasys Is a Promising Therapy for Chronic
Hepatitis B 01/23/04
Pegasys
Found More Effective Than Epivir-HBV in Treatment of Most Difficult to Treat Patients
with Chronic Hepatitis B 10/31/03
Treatment of Chronic Hepatitis
B with Pegasys Shows Improved Response Rate Compared to Roferon
01/08/03
05/16/05 Source
Roche
Pharmaceuticals. FDA Approves Pegasys as the First and Only Pegylated Interferon
for the Treatment of Chronic Hepatitis B. Press Release. May 13, 2005.
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