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FDA Approves Pegasys in Combination With Copegus (ribavirin) for HCV Treatment
Press Release from Roche
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FDA Approves Pegasys (peginterferon alfa-2a) in Combination with Copegus
(ribavirin) for the Treatment of Hepatitis C
New treatment offers dosing regimen based on hepatitis C virus strain
NUTLEY, N.J. (December 3, 2002) - Roche announced today that the U.S. Food
and Drug Administration (FDA) has approved combination therapy with Pegasys"
(peginterferon alfa-2a), a pegylated interferon, and 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. Patients
in whom efficacy was demonstrated included patients with compensated liver
disease and histological evidence of cirrhosis (Child-Pugh class A).
Pegasys and Copegus combination therapy was granted priority review
designation by the FDA. Pegasys was approved as monotherapy for the
treatment of adults with chronic hepatitis C on October 16, 2002. Currently,
2.7 million Americans are chronically infected with hepatitis C.
"Roche has taken a leadership role in advancing hepatitis C therapy by
researching approaches to reduce the duration of treatment with Pegasys and
Copegus and the dose of Copegus therapy for certain patients," George B.
Abercrombie, President & Chief Executive Officer - Hoffmann-La Roche Inc.
"Today, Roche can proudly offer Americans with hepatitis C a new treatment
choice‹Pegasys and Copegus combination therapy."
"Different genotypes of the hepatitis C virus need to be approached
differently. Certain genotypes of the hepatitis C virus are easier to treat
while others are stubborn and more difficult to treat," said Pegasys
investigator, David Bernstein, MD, Director of Hepatology at North Shore
University Hospital, Manhasset, NY. "With Pegasys combination therapy, we
can now tailor the dose and duration of a patient's therapy to the genotype
of the virus."
Pivotal Studies
Pegasys and Copegus combination therapy was granted approval based on the
results of two pivotal Phase III clinical trials that demonstrate it is an
effective treatment for patients with chronic hepatitis C.
The pivotal study completed most recently evaluated the effects of the
duration (24 weeks compared to 48 weeks) of Pegasys 180mcg as a subcutaneous
injection once weekly and Copegus treatment (24 weeks compared to 48 weeks)
and the daily dose of Copegus (800mg compared to 1000 for patients weighing
less than 75 kg and 1200 for patients equal to or more than 75 kg) in
patients with chronic hepatitis C. The number of patients who received
medication in the study was 1284.
The study showed that patients with strains of the hepatitis C virus known as
genotype non-1 (predominantly 2 and 3) achieved similar sustained virological
response rates when treated with a 24 week regimen of Pegasys and 800mg
Copegus compared to a 48 week regimen of Pegasys and 1000-1200 Copegus.
Genotype non-1 (predominantly 2 and 3) patients who were treated with the 24
week lower Copegus dose regimen experienced fewer side effects. Sustained
virological response refers to a patient's continued undetectable serum
hepatitis C RNA levels 24 weeks after finishing a course of treatment.
Genotype 1 patients who were treated with the a 48 week regimen of Pegasys
and 1000-1200 Copegus had higher sustained virological response rates
compared to those treated with the 24 week lower Copegus dose regimen.
Sustained virological response rates for these groups treated with Pegasys
and Copegus therapy were:
--Genotype 1: 48 week duration with 1000 - 1200mg Copegus: 51 percent
--Genotype non-1: 24 week duration with 800mg Copegus: 82 percent
The other pivotal study was published in the September 26, 2002 New England
Journal of Medicine and showed that Pegasys 180mcg and Copegus 1000 - 1200mg
combination therapy is a more effective treatment for chronic hepatitis C
than interferon alfa-2b 3 MIU as a subcutaneous injection three times a week
and 1000 - 1200mg ribavirin. The sustained virological response rate in the
Pegasys and Copegus treated patients was 53 percent compared to 44 percent in
the interferon alfa-2b and ribavirin group. The number of patients who
received medication in the study was 1121.
In both studies, virus genotype was clearly the strongest predictor of
whether or not a patient achieved a sustained virological response.
Pegasys, a premixed solution, is dosed at 180mcg as a subcutaneous injection
once a week. Copegus, available as a 200mg tablet, is administered at 800 to
1200mg taken twice daily as a split dose. Pegasys is currently available at
pharmacies. Copegus will be available in early 2003. The two products will
be sold separately.
About Pegasys
Pegasys is supported by the most extensive development program ever
undertaken for a
hepatitis C treatment. Pegasys has been studied in a variety of patient
populations, including those with the most difficult to treat form of the
disease - patients with genotype 1 and with cirrhosis (scarring of the liver).
Pegasys is made when interferon alfa-2a undergoes the process of pegylation
in which one or more chains of polyethylene glycol, also known as PEG, are
attached to another molecule.
In Pegasys, a large, branched, mobile PEG is bound to the interferon alfa-2a
molecule and provides a selectively protective barrier. Pharmacokinetic
behavior of the end product depends on the length of the PEG and the nature
of the link between the PEG and the protein. The high molecular weight (40
kilodalton) branched PEG in Pegasys has been shown to provide sustained
pegylated interferon alfa-2a exposure at clinically effective levels over the
one-week dosing period. Pegasys has been approved for use in more than 50 c
ountries, including all European Union countries.
Pegasys and Copegus Adverse Events
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. Patients with persistently severe or worsening signs
or symptoms of these conditions should be withdrawn from therapy. In many,
but not all cases, these disorders resolve after stopping Pegasys therapy.
Copegus may cause birth defects. Extreme care must be taken to avoid
pregnancy in female patients and in female partners of male patients taking
Pegasys and Copegus combination therapy. Ribavirin causes hemolytic anemia.
The anemia associated with ribavirin therapy may result in worsening of
cardiac disease.
Ribavirin is genotoxic, mutagenic, and should be considered a potential
carcinogen.
Pegasys is contraindicated in patients with hypersensitivity to Pegasys or
any of its components, autoimmune hepatitis, and decompensated hepatic
disease prior to or during treatment with Pegasys. Pegasys is also
contraindicated in neonates and infants because it contains benzyl alcohol.
Benzyl alcohol has been reported to be 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 women who are pregnant, men whose female partners are
pregnant and patients with hemoglobinopathies (eg, thalassemia major, sickle
-cell anemia).
The most common adverse events reported for Pegasys and Copegus combination
therapy, observed in clinical studies to date (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%).
Serious adverse events include neuropsychiatric disorders (suicidal ideation
and suicide attempt), serious and severe bacterial infections, 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 psoriasis and lupus),
pulmonary disorders (dyspnea, pneumonia, brochiolitis obliterans,
interstitial pneumonitis and sarcoidosis), colitis (ulcerative and
hemorrhagic/ischemiccolitis), pancreatitis, and opthalmologic disorders
(decrease or loss of vision, retinopathy including macular edema and retinal
thrombosis/hemorrhages, optic neuritis and papilledema).
The complete package inserts for Pegasys and Copegus are available at
www.pegasys.com, or by calling 1-877-PEGASYS.
About Hepatitis C
Hepatitis C, a blood-borne infectious disease of the liver, the leading cause
of cirrhosis and liver cancer and the number one reason for liver transplants
in the U.S., is transmitted through body fluids, primarily blood or blood
products, and by sharing needles. In many patients, the mode of transmission
is unknown. Unfortunately, most people infected with hepatitis C are unaware
of it because it may take years for symptoms to develop. Hepatitis C
chronically infects an estimated 170 million people worldwide (three percent
of the world's
population), with as many as 180,000 new cases occurring each year. It is
estimated that less than 30 percent of all cases are diagnosed. If left
untreated, hepatitis C can be fatal for some patients.
About Roche
Roche Molecular Diagnostics, a business unit of the Roche Group, manufactures
the COBAS AMPLICOR” HCV Test, v2.0 test for the detection of hepatitis C
virus in clinical specimens. Hoffmann-La Roche Inc. (Roche), based in Nutley,
N.J., is the U.S. prescription drug unit of the Roche Group, a leading
research-based health care enterprise that ranks among the world's leaders
in pharmaceuticals and diagnostics. Roche discovers, develops, manufactures
and markets numerous important prescription drugs that enhance people's
health, well-being and quality of life. Among the company's areas of
therapeutic interest are: dermatology; genitourinary disease; infectious
diseases, including influenza; inflammation, including arthritis and
osteoporosis; metabolic diseases, including obesity and diabetes; neurology;
oncology; transplantation; vascular diseases; and virology, including
HIV/AIDS and hepatitis C.
For more information on the Roche pharmaceuticals business in the United
States, visit the company's website at: www.rocheusa.com.
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