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Short
Course PegIntron plus Rebetol Approved in Europe for HCV Patients
with Genotype 1 and Low HCV Viral Load
The
European Commission has approved revised dosing instructions
that allow for a shorter, 24-week course of PegIntron
(1.5 mcg/kg once weekly) and Rebetol (800 – 1,200 mg daily)
combination therapy among a subgroup of patients
with chronic hepatitis C virus (HCV), according to an announcement
form Schering-Plough.
The revised
treatment regimen is specifically for chronic HCV patients
with genotype
1 infection and low viral
load (< 600,000 IU/ml) who have achieved
rapid
virologic response, defined as undetectable
virus (HCV-RNA negative) at week 4 of treatment
that is maintained through week 24.
Approval
of this shorter PegIntron and Rebetol combination treatment
regimen cuts by half the duration of therapy for a subset
of hepatitis C patients with genotype 1 and low viral load.
This is the only treatment regimen approved in the European
Union (EU) for a 24-week course of therapy in certain genotype
1 patients.
In clinical
studies supporting the approval, 92 percent of patients who
met the criteria for early response achieved a sustained
virologic response (SVR) with 24 weeks of treatment.
In the United States, PegIntron (1.5 mcg/kg
once weekly) is approved in combination with Rebetol (800
mg daily) for a duration of treatment of 48 weeks.
“Physicians
now have the opportunity to consider a shorter course of therapy
for their patients with hepatitis C genotype 1 who meet specific
criteria,” said Professor Stefan Zeuzem, M.D., Saarland University,
Homburg, Germany, and lead investigator of the study supporting
the approval. “Tailoring treatment so that those with an
early response are treated for only 24 weeks rather than 48
weeks may make therapy more appealing to patients, providing
comparable efficacy with better tolerability,” he said.
“Approval
of this shorter course of PegIntron and Rebetol combination
therapy reflects the ongoing commitment of Schering-Plough
to define optimal dose and treatment schedules to better meet
the needs of hepatitis C patients,” said Robert J. Spiegel,
M.D., chief medical officer and senior vice president of medical
affairs, Schering-Plough Research Institute.
The Commission
approval results in Marketing Authorization with unified labeling
that is valid in the current EU 25 member states as well as
in Iceland and Norway. PegIntron and Rebetol combination
therapy was previously approved in the EU for a 48-week course
of therapy for all patients with genotype 1 who exhibit virological
response at week 12.
Study Results
The approved
labeling change for PegIntron and Rebetol is based on results
of a clinical study involving 235 patients with HCV genotype
1 and low viral load who received 24 weeks of combination
therapy with PegIntron (1.5 mcg/kg once weekly) and Rebetol
(800 – 1,400 mg daily); only two patients weighing >105
kg received the 1,400 mg dose. In the study, 41 percent of
patients (97/235) had undetectable plasma HCV-RNA levels at
week 4 and week 24 of therapy. Patients in this subgroup
achieved a 92 percent (89/97) rate of sustained virological
response. The high SVR in this group of patients was identified
in an interim analysis and prospectively confirmed.
Genotype
1 virus is the most common worldwide, the most difficult to
treat successfully and accounts for about 70 percent of HCV
infections among European patients overall, varying by geography.
For patients with HCV genotypes 2 or 3, the EU labeling for
PegIntron recommends that all patients be treated for 24 weeks.
Patients infected with HCV genotype 4 are considered harder
to treat and generally 48 weeks of therapy is recommended.
In the United
States, PegIntron is indicated
in combination with Rebetol (800 mg daily) for 48 weeks.
About PegIntron and Rebetol Combination Therapy
PegIntron
and Rebetol combination therapy for chronic hepatitis C was
approved in the European Union in March 2001. The recommended
dose in the EU for combination therapy is PegIntron 1.5 mcg/kg
once weekly plus Rebetol 800-1,200 mg daily, adjusted to body
weight. PegIntron had previously received centralized marketing
authorization in the EU and is marketed as a monotherapy in
cases of intolerance or contraindication to ribavirin for
the treatment of adult patients with chronic
hepatitis C.
PegIntron,
recombinant interferon alfa-2b linked to a 12,000 dalton polyethylene
glycol (PEG) molecule, is a once-weekly therapy dosed according
to patient body weight that is designed to achieve an effective
balance between antiviral activity and elimination half-life.
Rebetol is an oral formulation of ribavirin,
a synthetic nucleoside analog
with broad-spectrum antiviral activity.
Chronic
hepatitis C is estimated to affect more than 10 million people
in major world markets, including 5 million in Europe. It
is a leading cause of chronic liver disease and one of the
most common reasons for liver transplant in Europe.
Important Information Regarding US Labeling for PEG-INTRON
and REBETOL
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WARNING
Alpha
interferons, including PEG-INTRON, 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 PEG-INTRON therapy.
Ribavirin
causes hemolytic anemia. Anemia associated with REBETOL
therapy may exacerbate cardiac disease that has led
to fatal and nonfatal myocardial infarctions. Patients
with a history of significant or unstable cardiac disease
should not be treated with REBETOL. It is advised that
complete blood counts (CBC) be obtained at baseline
and at weeks 2 and 4 of therapy or more frequently if
clinically indicated.
REBETOL
and combination REBETOL/PEG-INTRON therapy must not
be used by women, or male partners of women, who are
or may become pregnant during therapy and during the
6 months after stopping therapy. REBETOL and combination
REBETOL/PEG-INTRON therapy should not be initiated until
a report of a negative pregnancy test has been obtained
immediately prior to initiation of therapy. Women of
childbearing potential and men must use effective contraception
(at least two reliable forms) during treatment and during
the 6-month post-treatment follow-up period.
Significant
teratogenic and/or embryocidal effects have been demonstrated
for ribavirin in all animal species in which adequate
studies have been conducted. These effects occurred
at doses as low as one twentieth of the recommended
human dose of REBETOL. If pregnancy occurs in a patient
or partner of a patient during treatment or during the
6 months after treatment stops, physicians are encouraged
to report such cases by calling (800) 727-7064.
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PegIntron
plus Rebetol Articles Posted on HIV and hepatitis.com
10/07/05
Source
Schering-Plough.
SHORTER COURSE OF PEG-INTRON® AND REBETOL® COMBINATION
THERAPY
APPROVED IN EUROPEAN UNION FOR CERTAIN HEPATITIS C PATIENTS
WITH GENOTYPE 1 AND LOW VIRAL LOAD. Press Release. October
5, 2005.
Excerpt from the Doctor Is In Q and A for Hepatitis C---Mouth
Sores and Interferon
Question: “I have HVC genotype 1. I have been
on treatment for 6 months now. My HCV viral count dropped
from 970,000 at the start to 1300 at 3 months. I have
recently been getting sores in and around the mouth.
I am on Pegasys, Copegus, Neupogen, and Procrit. Are
mouth sores associated with any of these drugs?”--Chris
Answer: Mouth
sores are very common from the interferon. Sometimes they
are from herpes infections, that is, cold sores, but most
commonly just inflammation. They can be very annoying. We
often use Sanford’s solution,
antacids or steroid cream on the sores.
By
the way, that is a very good HCV viral load drop, and you
are well on your way to a cure! Keep up the good
work!—Douglas Dieterich, MD, Professor of Medicine,
Mount Sinai School of Medicine, NYC
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