Schering-Plough
Reports Top-line Results
of the IDEAL Study KENILWORTH,
N.J., Jan. 14, 2008 - Schering-Plough Corporation , a leader in hepatitis research,
today reported top-line results of the IDEAL study, the first large, randomized,
clinical study comparing the leading therapies for chronic hepatitis C: PEGINTRON
(peginterferon alfa-2b) and REBETOL (ribavirin, USP) combination therapy vs. Pegasys
(peginterferon alfa-2a) and Copegus (ribavirin, USP) combination therapy, [1]
as well as a lower dose of PEGINTRON in an investigational combination
regimen. The
results showed that sustained virologic response (SVR), [2]
the primary endpoint of the study, was similar for the two leading
combination therapies for hepatitis C; and that using a lower dose of PEGINTRON
with REBETOL also resulted in a similar SVR. The study also showed that fewer
patients treated with both PEGINTRON regimens relapsed after the end of treatment
compared to those receiving Pegasys and Copegus. In
the IDEAL (Individualized Dosing Efficacy vs. Flat Dosing to Assess optimaL pegylated
interferon therapy) study, both PEGINTRON regimens utilized investigational weight-based
ribavirin dosing. The three treatment regimens studied were: (1)
PEGINTRON 1.5 mcg/kg/week and REBETOL 800-1,400 mg/day;
(2) PEGINTRON
1.0 mcg/kg/week and REBETOL 800-1,400 mg/day; and
(3) Pegasys 180
mcg/week and Copegus 1,000-1,200 mg/day
In
the study, 3,070 previously untreated U.S. patients with HCV genotype 1, the most
common form of the virus worldwide and most difficult to treat, were randomized
to one of the three treatment regimens and received up to 48 weeks of combination
therapy with 24 weeks of follow-up. SVR,
the primary endpoint of the study, was similar for the three treatment regimens
(40 vs. 38 vs. 41 percent, respectively). Importantly,
while end of treatment response was higher in the Pegasys combination therapy
arm, IDEAL showed that fewer patients receiving PEGINTRON combination therapy
relapsed after the end of treatment (24 vs. 20 vs. 32 percent, respectively).
Overall adverse
events reported for the three treatment regimens were similar and, as seen in
other studies with these treatments, a range of "flu-like symptoms"
were the most commonly reported adverse events for all three treatment regimens.
Discontinuation rates due to adverse events also were similar (13 vs. 10 vs. 13
percent, respectively). "While
the sustained response rates were similar in the IDEAL study, we were pleased
to see that fewer patients relapsed following PEGINTRON combination therapy,"
said Robert J. Spiegel, M.D., chief medical officer and senior vice president,
Schering-Plough Research Institute. "With
these results, we now have, for the first time, a large body of well-controlled
clinical data demonstrating how the similarities and differences of the two leading
combination therapies for hepatitis C affect outcomes for patients. These findings
provide important clinical-based evidence that will help physicians in making
treatment decisions and in guiding their patients through what is a long and challenging
course of therapy. We look forward to further analyses of this large data set
to gain additional clinical insights into the management of this serious disease." In
IDEAL, the combination regimen of Pegasys and Copegus used the recommended doses
in accordance with their approved U.S. labeling, which includes a flat dose of
Pegasys (180 mcg/week) for all patients regardless of body weight, and 1,000 or
1,200 mg/day of Copegus, adjusted for two weight categories. PEGINTRON
was dosed either at 1.5 mcg/kg/week or an investigational combination dose of
1.0 mcg/kg/week with REBETOL at an investigational dose of 800-1,400 mg/day, adjusted
by four weight categories. As a result, the majority of patients (1598/3070, 52
percent) were assigned the same dose of ribavirin (either REBETOL or Copegus)
based on their weight groups. In
the study, 39 percent of patients in the Pegasys arm were assigned a higher dose
of ribavirin, while 9 percent of patients in the PEGINTRON arms were assigned
a higher dose of ribavirin. Among
those who were assigned equivalent doses of ribavirin based on their weight group,
SVR also was similar (40 vs. 38 vs. 38 percent, respectively). Also, fewer of
these patients treated with PEGINTRON and REBETOL relapsed after the end of therapy
compared with those treated with Pegasys and Copegus (22 vs. 20 vs. 35 percent,
respectively). Complete
results of the IDEAL study will be submitted for peer-reviewed publication and
for presentation at upcoming medical meetings, as well as to Health Authorities
worldwide. About
IDEAL The
IDEAL study was undertaken by Schering-Plough as an important step in meeting
the needs of the hepatitis C medical and patient communities to identify improved
treatment strategies to optimize outcomes for patients. IDEAL,
a Phase IIIb, randomized, parallel-group study, was conducted at 118 academic
and community centers across the United States. The
study treated 3,070 adult patients with chronic HCV genotype 1. Of these, 82 percent
of patients had high viral load (greater than or equal to 600,000 IU/mL), [3]
11 percent had grade F3/4 fibrosis/cirrhosis, and 19 percent were African Americans.
There were no significant differences in patient demographics or disease characteristics
across the three treatment arms The
comparison of the two PEGINTRON combination therapy doses (1.5 vs. 1.0 mcg/kg/week)
was conducted as a post-approval commitment to the U.S. Food and Drug Administration
(FDA). The comparison of the PEGINTRON and Pegasys combination therapy regimens
was added to the study because no randomized, controlled head-to-head study of
the two available peginterferon regimens had been conducted to date. Cross-study
comparisons and retrospective analyses of previous data are difficult to interpret
because of differences in study designs, patient populations and assay limits.
John McHutchison,
M.D., and Mark Sulkowski, M.D., are the co-principal investigators of the IDEAL
study. They also are co-chairmen of the IDEAL Publication Committee, which also
includes three independent expert members not associated with the study to assure
an unbiased evaluation of the data. The
Publication Committee was responsible for the preparation of the prespecified
data analysis plan for the statistical analysis conducted for the primary publication
of the study results. References:
1.
Pegasys and Copegus are registered trademarks of Hoffmann-La Roche Inc. Please
see the Pegasys and Copegus product inserts for information on these products. 2.
SVR, the protocol specified primary efficacy endpoint, is defined as achievement
of undetectable HCV-RNA at 24 weeks after the end of treatment. Per protocol,
if a patient did not have a 24-week post-treatment assessment, the patient's 12-week
post-treatment assessment was utilized. 3.
Roche Cobas Taqman 1.0 assay; lower limit of detection is 15 IU/mL. | 
