European Union Approves Pegintron (Peginterferon Alfa-2b) For Hepatitis
MADISON, NJ -- May 30, 2000
-- Schering-Plough Corporation announced that the European Union's (EU)
Commission of the European Communities has granted marketing authorization
to Pegintron™ (peginterferon alfa-2b) as once-weekly monotherapy for the
treatment of adult patients with chronic hepatitis C. Pegintron is the first
pegylated interferon approved for marketing in the world.
In clinical studies, once-weekly administration of Pegintron has been shown
to be twice as active and just as well tolerated as Schering-Plough's Intron(R)
A (interferon alfa-2b, recombinant) Injection, the world's largest-selling
alpha interferon, administered three times weekly as monotherapy for
Pegintron is a longer-acting form of Intron A that uses proprietary PEG
technology developed by Enzon, Inc. of Piscataway, N.J. Schering-Plough
holds an exclusive worldwide license to Pegintron. Commission approval of
the centralized application for Pegintron results in a single Marketing
Authorization with unified labeling that is immediately valid in all 15
EU-Member States. The Commission's decision follows the product's unanimous
recommendation for approval in February 2000 by the EU's Committee for
Proprietary Medicinal Products (CPMP) of the European Agency for the
Evaluation of Medicinal Products (EMEA).
Pegintron will be introduced upon receiving pricing approvals, where
necessary, from individual EU countries.
Pegintron is indicated as monotherapy in case of intolerance or
contraindication to ribavirin for the treatment of adult patients with
histologically proven chronic hepatitis C who have serum markers indicating
virus replication, e.g., those patients who have elevated transaminases
without liver decompensation and who are positive for serum HCV-RNA or
The approved labeling in the EU for Pegintron indicates that the optimal
treatment for chronic hepatitis C is considered to be the administration of
a combination of interferon alfa-2b with ribavirin. The safety and efficacy
of the combination of Pegintron and ribavirin has not yet been documented.
Pegintron monotherapy is administered subcutaneously at a dose of 0.5 or 1.0
mcg/kg once weekly for at least six months. In patients showing loss of
HCV-RNA at six months, treatment is continued for an additional six months,
i.e. for a total course of treatment of one year.
A worldwide, controlled clinical study designed to establish the activity
and tolerance of Pegintron versus Intron A monotherapy was conducted in
adult patients with previously untreated chronic hepatitis C and compensated
liver disease. A total of 1,219 patients, who were positive for serum
HCV-RNA and who had elevated liver enzymes (serum alanine aminotransferase),
were treated with one of three doses of Pegintron (0.5, 1.0, 1.5 mcg/kg)
administered once weekly or Intron A (3 MIU) administered three times weekly
for 48 weeks. The primary efficacy endpoint of the study was sustained loss
of detectable HCV-RNA at 24 weeks from the end of 48 weeks of treatment.
Pegintron at all three doses studied was shown to be superior to, and as
safe as, Intron A in treating all HCV genotypes.
The study results showed that sustained virologic responses were achieved in
25 percent of patients receiving Pegintron 1.0 mcg/kg and 18 percent of
patients receiving Pegintron 0.5 mcg/kg, compared to 12 percent of patients
receiving Intron A. In patients having genotype 2 or 3 and low viral load
(<2 million copies/ml), sustained virologic responses were achieved in 62
percent of patients treated with Pegintron 1.0 mcg/kg and 58 percent of
patients treated with Pegintron 0.5 mcg/kg, compared to 36 percent of
patients treated with Intron A.
The demographic/disease characteristics of patients in this study were
similar to those in previous Schering-Plough hepatitis C registration
studies, with a majority of patients having genotype 1, the most difficult
genotype to treat (70 percent genotype 1), and high viral load (74 percent
HCV-RNA>2 million copies/ml).
Adverse events (AEs) for all doses of Pegintron were similar to those for
Intron A. Most AEs were mild to moderate and were manageable with dose
adjustment. Discontinuation of therapy due to AEs was similar for all
treatment groups (6-11 percent). Dose reductions were similar for Intron A
and Pegintron 0.5 mcg/kg and higher for Pegintron 1.0 and 1.5 mcg/kg (6
percent, 9 percent, 14 percent and 19 percent, respectively). The most
common side effects occurring with Pegintron were "flu-like"
symptoms, such as headache, fatigue, myalgia and fever, which appeared to
decrease in severity as treatment continued.
Chronic hepatitis C is estimated to affect some 10 million people in major
world markets. As many as 5 million Europeans (1 to 2 percent of the general
population) are chronically infected with the hepatitis C virus, according
to a study conducted by the World Health Organization (WHO). In Europe,
chronic hepatitis C is the leading cause of chronic liver disease and the
most common reason for liver transplant.
In the United States, Schering-Plough on Dec. 23, 1999, submitted a
Biologics License Application (BLA) to the U.S. Food and Drug Administration
(FDA) seeking marketing approval for PEG-Intron(TM) (peginterferon alfa-2b)
Powder for Injection as once-weekly monotherapy for the treatment of chronic
hepatitis C. Some 4 million Americans are chronically infected with the
hepatitis C virus, according to the Centers for Disease Control and
Intron A is a recombinant version of naturally occurring alpha interferon,
which has been shown to exert both antiviral and immunomodulatory effects.
Schering-Plough markets Intron A worldwide for 16 major antiviral and
Rebetol® (Ribavirin, USP) Capsules is an oral formulation of ribavirin, a
synthetic nucleoside analog with broad-spectrum antiviral activity.
Schering-Plough has exclusive rights to market oral ribavirin for hepatitis
C in all major world markets through a licensing agreement with ICN
Pharmaceuticals, Inc. of Costa Mesa, Calif.
Schering-Plough is a research-based company engaged in the discovery,
development, manufacturing and marketing of pharmaceutical products