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
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
(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.