Approves an Expanded Indication for
Peginterferon-based Combination Therapy
Patients with Chronic Hepatitis C
NJ -- March 11, 2009 -- Schering-Plough Corporation today announced that the U.S.
Food and Drug Administration (FDA) has approved new labeling for PegIntron (peginterferon
alfa-2b) and Rebetol (ribavirin, USP) combination therapy for treating chronic
hepatitis C in patients 3 years of age and older with compensated liver disease.
With approval of this expanded indication, PegIntron and Rebetol is the first
and only pegylated interferon combination therapy approved in the United States
that is not restricted to treatment-naive patients.
less likely to benefit from retreatment after failing a course of therapy include
those with previous nonresponse, previous pegylated interferon treatment, significant
bridging fibrosis or cirrhosis,
or HCV genotype 1 infection. It is
estimated that more than 100,000 patients in the United States failed prior treatment
of their hepatitis C virus (HCV) infection, representing a large and growing patient
the FDA approval of PegIntron and Rebetol combination therapy for this new indication,
U.S. physicians now have a treatment option that offers a second chance for success
to certain patients who failed prior therapy," said Robert J. Spiegel, MD,
chief medical officer and senior vice president, Schering-Plough Research Institute.
"This approval further underscores Schering-Plough's leadership and long-term
commitment to developing new treatment options and innovative therapies to meet
the needs of patients with hepatitis C."
from the clinical study supporting the approval helped to define those patient
groups most likely to respond to retreatment as well as those unlikely to respond.
Overall, previous relapsers, patients with HCV
genotype 2 or 3, or those initially treated with non-pegylated interferon
therapy achieved higher rates of sustained virologic response (SVR) [SVR is defined
as achievement of undetectable HCV RNA at 24 weeks] than patients with previous
nonresponse, previous pegylated interferon treatment, significant bridging fibrosis
or cirrhosis, or HCV genotype 1 infection.
"Based on a patient's
treatment history, physicians can identify which patients may be right for retreatment
with PegIntron combination therapy and may have the best chance to achieve a sustained
response," said Eugene R. Schiff, MD, director, Center for Liver Diseases,
University of Miami Miller School of Medicine, and a lead investigator for the
clinical study on which the approval was based. "Conversely, patients with
certain treatment characteristics who are unlikely to respond to this regimen
can be advised accordingly."
the clinical study supporting the approval, achievement of undetectable virus
(HCV RNA) at treatment week 12 was a strong predictor of SVR. Patients who still
had detectable virus at week 12 of therapy were highly unlikely to achieve SVR.
with undetectable virus at week 12 have a better chance for success and can be
motivated to continue treatment," Schiff added, "and those patients
who fail to achieve an early response can have their therapy stopped with confidence,
thus avoiding unnecessary treatment and potential adverse events."
approval of PegIntron for the expanded indication is based on the results of one
of the clinical studies in the EPIC 3 program: a noncomparative trial in which
2,293 adult patients with moderate-to-severe fibrosis or cirrhosis who failed
previous treatment with combination alpha interferon/ribavirin were retreated
with PegIntron (1.5 mcg/kg once weekly) in combination with weight-adjusted Rebetol
(800-1,400 mg daily).[EPIC 3 (Evaluation of PegIntron in Control of Hepatitis
C Cirrhosis), a large multicenter global clinical study evaluating the benefits
of PegIntron in fibrotic and cirrhotic patients.]
patients had received at least 12 weeks of combination therapy and included prior
nonresponders (patients who were HCV RNA positive at the end of a minimum 12 weeks
of treatment) and prior relapsers (patients who were HCV RNA negative at the end
of treatment and subsequently relapsed after post-treatment follow-up). In the
study, patients who were HCV RNA negative at week 12 were treated for a total
of 48 weeks and followed for 24 weeks post-treatment. Response to treatment was
defined as undetectable HCV RNA at 24 weeks post-treatment.
overall response rate in the study was 22 percent (497/2,293). Response rates
among relapsers overall were 43 percent (130/300) and 35 percent (113/344) for
patients previously treated with non-pegylated or pegylated alpha interferon and
ribavirin combination therapy, respectively. The response rates in nonresponders
overall were 18 percent (158/903) and 6 percent (30/476), respectively.
the study, 1,470 (64 percent) patients did not achieve undetectable HCV RNA at
treatment week 12, and were offered enrollment into long-term treatment trials,
due to an inadequate treatment response.
the 823 (36 percent) patients who were HCV RNA undetectable at treatment week
12, those infected with HCV genotype 1 had an SVR rate of 48 percent (245/507),
with a range of responses by fibrosis score (F4-F2) of 39-55 percent. Patients
infected with HCV genotype 2 or 3 who were HCV RNA undetectable at treatment week
12 had an overall SVR of 70 percent (196/281), with a range of responses by fibrosis
score (F4-F2) of 60-83 percent. For all HCV genotypes, higher fibrosis scores
were associated with a decreased likelihood of achieving SVR.
recommended treatment duration with PegIntron combination therapy for patients
who failed prior treatment is 48 weeks, regardless of HCV genotype. Retreated
patients who have detectable HCV-RNA at week 12 or 24 are highly unlikely to achieve
SVR and discontinuation of therapy should be considered.
receiving PegIntron and Rebetol as retreatment after failing a previous interferon
combination regimen reported adverse reactions similar to those previously associated
with this regimen during clinical trials of treatment-naive patients.
the United States, PegIntron is indicated for use in combination with ribavirin
in patients 3 years of age or older, and as monotherapy in patients 18 years of
age and older, for the treatment of chronic hepatitis C in patients with compensated
liver disease. Patients with the following characteristics are less likely to
benefit from retreatment after failing a course of therapy: previous nonresponse,
previous pegylated interferon treatment, significant bridging fibrosis or cirrhosis,
and genotype 1 infection.
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