Results of PEG-INTRON(R) and REBETOL(R) Study in Retreating Hepatitis C Patients Who Failed Previous Combination Therapy Present
2006年10月27日 - 10:30PM
PRニュース・ワイアー (英語)
BOSTON, Oct. 27 /PRNewswire-FirstCall/ -- Schering-Plough today
reported data from EPIC3, a large ongoing clinical study, showing
that retreatment with PEG-INTRON(R) (peginterferon alfa-2b) and
REBETOL(R) (ribavirin, USP) combination therapy can result in
sustained virologic response(1) (SVR) in patients with chronic
hepatitis C who failed previous treatment with any alpha
interferon-based combination therapy, including peginterferon
regimens. In this study, 56 percent of patients who had
undetectable virus (HCV-RNA) after 12 weeks went on to achieve SVR
with a 48-week course of therapy. Of the first 1,354 patients
retreated, approximately 38 percent had undetectable virus at week
12. Importantly, patients who did not have undetectable virus at 12
weeks had little chance of achieving SVR. Overall, 23 percent of
patients achieved SVR. "The ability to predict efficacy of
retreatment early in the course of therapy would assist physicians
in managing this hard-to-treat patient population," said Eugene R.
Schiff, M.D., chief, division of hepatology and director, Center
for Liver Disease, University of Miami Miller School of Medicine,
and co-lead investigator of the EPIC3 study. "These results suggest
undetectable viral load at week 12 defines an early virologic
response that predicts SVR for patients who failed previous
combination therapies and are retreated with PEG-INTRON and
REBETOL." Data from the EPIC3 retreatment study are being presented
here at the 57th Annual Meeting of the American Association for the
Study of Liver Diseases (AASLD).(2) "A large and growing number of
patients who failed previous HCV therapy are in need of viable
treatment options," said Robert J. Spiegel, M.D., chief medical
officer and senior vice president, Schering-Plough Research
Institute. "The results of this study demonstrate that retreatment
with PEG-INTRON and REBETOL combination therapy may help address
this unmet medical need in this difficult-to-treat patient
population." Hepatitis C virus (HCV) infection is a major cause of
chronic liver disease and is a significant healthcare problem
worldwide. The current standard of care for treating chronic HCV is
the combination of peginterferon and ribavirin, which achieves SVR
in approximately 50 to 60 percent of patients overall.(3,4) EPIC3
Data Presented at AASLD EPIC3 (Evaluation of PEG-INTRON in Control
of Hepatitis C Cirrhosis) is a large multicenter global clinical
study program involving a total of more than 2,200 patients at
approximately 140 sites worldwide. The program includes a global,
multicenter, open-label, single-arm prospective study designed to
assess the safety and efficacy of retreatment with PEG-INTRON and
REBETOL combination therapy in patients with moderate-to-severe
fibrosis (METAVIR F2- F4) who failed previous treatment with any
interferon-alfa plus ribavirin combination therapy, including
peginterferon-based regimens (peginterferon alfa-2a or
peginterferon alfa-2b). In this non-comparative study, patients
were retreated with PEG-INTRON (1.5 mcg/kg once weekly) in
combination with weight-based dosed REBETOL (800-1,400 mg/daily)
for up to 48 weeks. The primary end point of the study was SVR,
defined as undetectable plasma HCV-RNA 24 weeks after the end of
treatment. An aim of the study was to further characterize early
viral response at week 12 as a predictor of SVR in these patients.
The data presented at AASLD included safety and efficacy results
for the first 1,354 patients retreated in the study. Of these, 77
percent of patients failed previous interferon-alfa plus ribavirin
therapy and 23 percent failed previous peginterferon plus ribavirin
therapy; 64 percent were characterized as nonresponders, 24 percent
as relapsers and 12 percent were uncategorized treatment failures.
Overall, 23 percent of retreated patients achieved SVR. Of those
who attained a greater than or equal to 2 log decrease in viral
load at week 12, 37 percent achieved SVR. Among patients who had
undetectable HCV-RNA at week 12, 56 percent achieved SVR. However,
only 6 percent of those who attained a 2 log decrease in HCV-RNA
but had detectable virus at week 12 achieved SVR. Of this latter
group, 17 percent of patients with very low viral load at week 12
(less than or equal to 100 IU) achieved SVR compared to 5 percent
of those with residual viral load (greater than 100-250 IU) and no
patients with HCV- RNA greater than 750 IU. About PEG-INTRON
PEG-INTRON is approved in the United States as monotherapy and for
use in combination therapy with REBETOL (800 mg/day) for the
treatment of chronic hepatitis C in patients with compensated liver
disease who are at least 18 years of age. Important Safety
Information Regarding U.S. Labeling for PEG-INTRON and REBETOL
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. PEG-INTRON There are no new
adverse events specific to PEG-INTRON as compared to INTRON(R) A
(interferon alfa-2b, recombinant) for Injection, however, the
incidence of some (e.g., injection site reactions, fever, rigors,
nausea) were higher. The most common adverse events associated with
PEG-INTRON were "flu- like" symptoms, occurring in approximately
50% of patients, which may decrease in severity as treatment
continues. Application site disorders were common (47%), but all
were mild (44%) or moderate (4%) and no patient discontinued, and
included injection site inflammation and reaction (i.e., bruise,
itchiness, irritation). Injection site pain was reported in 2% of
patients receiving PEG-INTRON. Alopecia (thinning of the hair) is
also often associated with alpha interferons including PEG-INTRON.
Psychiatric adverse events, which include insomnia, were common
(57%) with PEG-INTRON, but similar to INTRON A (58%). Depression
was most common at 29%. Suicidal behavior including ideation,
suicidal attempts, and completed suicides occurred in 1% of
patients during or shortly after completing treatment with
PEG-INTRON. PEG-INTRON/REBETOL is contraindicated in patients with
autoimmune hepatitis, decompensated liver disease, and in patients
with hemoglobinopathies (e.g., thalassemia major, sickle-cell
anemia). The following serious or clinically significant adverse
events have been reported at a frequency less than or equal to 1%
with PEG-INTRON or interferon alpha: Severe decreases in neutrophil
or platelet counts, hypothyroidism, hyperglycemia, hypotension,
arrhythmia, ulcerative and hemorrhagic colitis, development or
exacerbation of autoimmune disorders including thyroiditis, RA,
systemic lupus erythematosus, psoriasis, pulmonary disorders
(dyspnea, pulmonary infiltrates, pneumonitis and pneumonia, some
resulting in patient deaths), urticaria, angioedema,
bronchoconstriction, anaphylaxis, retinal hemorrhages, and cotton
wool spots. In the PEG-INTRON/REBETOL combination trial the
incidence of serious adverse events was 17% in the
PEG-INTRON/REBETOL groups compared to 14% in the INTRON A/REBETOL
group. The incidence of severe adverse events in the PEG-
INTRON/REBETOL combination therapy trial was 23% in the INTRON
A/REBETOL group and 31-34% in the PEG-INTRON/REBETOL groups. Dose
reductions due to adverse reactions occurred in 42% of patients
receiving PEG-INTRON (1.5 mcg/kg)/ REBETOL and in 34% of those
receiving INTRON A/REBETOL. REBETOL should not be used in patients
with creatinine clearance less than 50 mL/min. Schering-Plough is a
global science-based health care company with leading prescription,
consumer and animal health products. Through internal research and
collaborations with partners, Schering-Plough discovers, develops,
manufactures and markets advanced drug therapies to meet important
medical needs. Schering-Plough's vision is to earn the trust of the
physicians, patients and customers served by its more than 32,000
people around the world. The company is based in Kenilworth, N.J.,
and its Web site is http://www.schering-plough.com/.
SCHERING-PLOUGH DISCLOSURE NOTICE: The information in this press
release includes certain "forward-looking statements" within the
meaning of the Securities Litigation Reform Act of 1995, including
statements related to regulatory approvals for PEG-INTRON and
REBETOL. Forward-looking statements relate to expectations or
forecasts of future events. Schering-Plough does not assume the
obligation to update any forward-looking statement. Many factors
could cause actual results to differ materially from
Schering-Plough's forward-looking statements, including market
forces, economic factors, product availability, patent and other
intellectual property protection, current and future branded
generic or over-the-counter competition, the regulatory process,
and any developments following regulatory approval, among other
uncertainties. For further details about these and other factors
that may impact the forward-looking statements, see
Schering-Plough's Securities and Exchange Commission filings,
including Item 1A. Risk Factors in the Company's second quarter
2006 10-Q. References 1 Sustained virologic response (SVR) is
defined as undetectable virus (HCV-RNA) levels in the blood at 6
months after the end of therapy. 2 HCV-RNA Negativity After 12
Weeks of Therapy Is the Best Predictor of Sustained Viral Response
(SVR) in the Retreatment of Previous Interferon alfa/Ribavirin
Nonresponders (NR): Results From the EPIC3 Program; T. Poynard et
al.; Poster No. 1123; American Association for the Study of Liver
Diseases (AASLD) 2006. 3 Manns et al., Lancet 2001;358:958-65. 4
Fried et al., N Engl J Med 2002;347:975-82. DATASOURCE:
Schering-Plough Corporation CONTACT: Media, Robert Consalvo,
+1-908-298-7409; or Investors, Alex Kelly, +1-908-298-7436; Robyn
Brown, +1-908-298-7436 Web site: http://www.schering-plough.com/
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