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This excerpt taken from the ELN 6-K filed Oct 28, 2009. Dublin, Ireland; San Diego – October
27, 2009 – Elan Corporation, plc (NYSE: ELN) and Biogen Idec (NASDAQ:
BIIB) today announced data showing that treatment with TYSABRI®
(natalizumab) significantly reduced the rate of hospitalization compared with
placebo in patients with moderate–to–severe Crohn’s disease during both
induction and maintenance treatment. These results were obtained from
retrospective subset analyses of three registrational Phase 3 trials (ENACT-1
[Efficacy of Natalizumab as Active Crohn’s Therapy]), (ENACT-2 [Evaluation of
Natalizumab as Continuous Therapy] and ENCORE [Efficacy of Natalizumab in
Crohn’s Disease Response and Remission]), and one open-label study (ENABLE
[Evaluation of the Natalizumab Antibody for Long-term Efficacy]). The data were
presented for the first time in an oral session at the American College of
Gastroenterology Annual Scientific Meeting in San Diego.
“Hospitalization
accounts for a large proportion of the cost of Crohn’s disease management,” said
Corey A. Siegel, M.D., director, Inflammatory Bowel Disease Center,
Dartmouth-Hitchcock Medical Center in Lebanon, N.H., and lead author of the
subset analysis. “Therefore, we were encouraged to see that TYSABRI reduced
hospitalization rates, particularly in the more difficult-to-treat subsets of patients previously
treated with anti-TNFα therapy.”
The
retrospective subset analysis evaluated the effect of TYSABRI on the rate of
hospitalization during induction and maintenance treatment using pooled data
from the ENACT-1 and ENCORE trials. In those trials, patients with
Crohn’s disease were randomized to intravenous TYSABRI 300 mg or placebo every
four weeks for three doses. The maintenance analysis was conducted
on -1-
TYSABRI
responders in ENACT-1 who were re-randomized and followed for an additional 48
weeks of therapy in ENACT-2. Data on patients losing response in
ENACT-2 who rolled over to an open-label study (ENABLE) supplemented the ENACT-2
data. Rates of all-cause hospitalization and Crohn’s disease-related
hospitalization per 100 patients over the 84-day induction period and the
336-day maintenance periods were evaluated.
Results
of the subset analysis showed that hospitalization rates were significantly
lower in patients treated with TYSABRI when compared with placebo. Two
physicians, blinded to treatment, reviewed all data to determine
hospitalizations and surgeries and whether they were, or were not, related to
Crohn’s disease. Out of the approximately 1500 patients involved in these
trials, the total number of all-cause hospitalizations was (n=136). In those
patients treated with TYSABRI, the rate of all-cause hospitalizations was
reduced by 35% (p=0.009) during the induction
period and 44% (p=0.044) during the
maintenance period. The total number of Crohn’s disease-related
hospitalizations was (n=109). In these Tysabri-treated patients, the rate
was reduced by 31% (p<0.001) during the
induction period and 58% (p=0.027) during the
maintenance period.
In
patients who had received prior anti-TNF therapy, a more difficult-to-treat
patient population, the benefit of TYSABRI was higher. During the
induction period, the total number of all-cause hospitalizations was
(n=57). In these patients, the rate was reduced by 56% (p=0.031) and Crohn’s
disease-related hospitalization (n=46) the rate was reduced by 55% (p=0.052). During the
maintenance period, all-cause hospitalization rate was reduced by 60% (p=0.034) and the Crohn’s
disease-related hospitalization rate was reduced by 75% (p=0.029).
“The
results of this analysis showing reduced hospitalization rates, together with
subset data previously announced at Digestive Disease Week in May, provide
additional support that TYSABRI is an important treatment option for patients
with this chronic and debilitating disease who have failed
anti-TNFα
therapies,” said Elan President Carlos V. Paya, M.D.,
Ph.D. “TYSABRI continues to show benefits in improving quality of
life, in CD patients, as well as in multiple sclerosis patients who also exhibit
benefits across clinical and radiological measures.”
Natalizumab
Reduces the Rate of Hospitalization in Moderate to Severe Crohn’s Patients: Data
from the ENACT and ENCORE Trials, Siegel, CA, Sands BE, Feagan B, et al.
Presented at the American College of Gastroenterology Annual Scientific Meeting,
October 27, 2009. Abstract #41.
About
ENACT-1, ENACT-2, ENCORE, and ENABLE
ENACT-1
involved patients with moderately to severely active Crohn's disease who
received wither TYSABRI 300 mg or placebo for 3 infusions. The
primary endpoint was clinical response at week 10. Patients who
responded to therapy were eligible to enroll into ENACT-2.
ENACT-2
presented maintenance data for an additional year of TYSABRI therapy among
patients with an initial response to TYSABRI, after 3 months in ENACT-1. Of
patients with response in ENACT-1, sustained response during ENACT-2 was seen in
61% of patients treated with TYSABRI at every visit through an additional 6
months of therapy, compared to 29% for placebo. This treatment difference was
also sustained through 12 months of additional therapy -2-
(54% vs.
20%). Remission was maintained at every visit with an additional 6 months or 12
months of TYSABRI in 45% and 40% of patients, respectively, compared to 26% and
15% of placebo treated patients (p<0.005 at 6 months). Among the patients that had previously
failed anti-TNFα therapy, response and remission was sustained at every visit
through an additional 6 months of TYSABRI in 52% and 30% of patients,
respectively. Given the requirement to discontinue chronic steroids, among the
subset of patients (n=65) on steroids and in whom a clinical response was
achieved, approximately two-thirds were able to discontinue steroids within 10
weeks of beginning to taper steroids. Although permitted in the clinical trials,
combination therapy with immunosuppressants is not recommended.
Data from
the second induction trial, ENCORE, showed that TYSABRI induced response and
remission among patients with moderately to severely active Crohn's disease, and
objective evidence of inflammation, as measured by elevated C-reactive
protein.
After 12
weeks of therapy, 60% of TYSABRI-treated patients attained response, compared to
44% of placebo treated patients, and 48% of patients showed a response at both
weeks 8 and 12, compared to 32% of placebo treated patients (p<0.005 for
both). Among the patients who had inadequate response to prior treatment with
inhibitors of TNFα, 38% achieved a response at weeks 8 and
12.
ENABLE
was an open-label extension study, which treated over 1000 patients with
TYSABRI, for up to an additional 12 months.
About
Crohn's disease
An
estimated 500,000 people in the United States have Crohn's disease, a chronic
and progressive inflammatory disease of the gastrointestinal tract, which
commonly affects both men and women.
The
disease usually causes diarrhea and crampy abdominal pain, often associated with
fever, and at times rectal bleeding. Loss of appetite and weight loss also may
occur. Complications include narrowing of the intestine, obstruction, abscesses,
and fistulas (abnormal channels connecting the intestine and other organs,
including the skin), and malnutrition. Most patients eventually require surgery,
which has both risks and potential short- and long-term
complications.
Crohn's
disease can have a devastating impact on the lifestyle of patients, many of whom
are young and active. Currently there is no medical or surgical cure for Crohn's
disease. Many patients fail to respond to current therapies, including
biological therapies such as agents that inhibit tumor necrosis factor alpha
(TNF-alpha). Due to this failure of current therapies in CD, therapies that have
alternate biological targets provide patients and physicians with therapeutic
options.
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