This excerpt taken from the ELN 6-K filed Jun 1, 2009.
Dublin, Ireland; Chicago, IL – May 31, 2009 – Elan Corporation, plc (NYSE: ELN) and Biogen Idec (NASDAQ: BIIB) shared data today that TYSABRI® (natalizumab) improved health related quality of life (QOL) in Crohn’s Disease (CD) patients who had previously been exposed to or failed anti-TNFα therapy versus placebo. These results were obtained from subset analyses of the Phase 3 ENACT-2 (Evaluation of Natalizumab as Continuous Therapy) and ENCORE (Efficacy of Natalizumab in Crohn’s Disease Response and Remission) trials and were presented today at Digestive Disease Week in Chicago.
QOL was measured using the patient-reported, disease-specific Inflammatory Bowel Disease Questionnaire (IBDQ), which measures bowel function, emotional function, systemic function, and social function. The Short-form 36 (SF-36), a general measure of QOL including physical function, bodily pain, general health, social function, mental health and vitality, was also used. In the 12-week ENCORE induction trial, patients receiving TYSABRI (n=89) who had failed previous anti-TNFα therapy achieved statistically significant improvements compared with those receiving placebo (n=83) on the total IBDQ scale and the two summary scales of the SF-36, the Physical Component Summary and the Mental Component Summary.
In the ENACT-2 maintenance trial, patients classified as responders to TYSABRI and who had an inadequate response to anti-TNFα therapy (n=32) had total IBDQ scores above 170, a level consistent with remission, throughout the length of the trial. These levels were significantly higher than placebo (n=40) at all measurements (P<0.05 at weeks 24, 36, 48, and 60). In addition, at week 60 of therapy, there was no clinically meaningful difference (i.e. <5 points) between patients receiving TYSABRI and the general population on seven of the eight individual
scales of the SF-36. While the ability to improve the QOL of patients who have failed previous anti-TNFα therapy is important, a larger clinical question is whether these improvements can be sustained during long-term therapy.
Brian Feagan, M.D., of the Robarts Research Institute at the University of Western Ontario, and first author of a manuscript published in the American Journal of Gastrointerology1 detailing the effects of TYSABRI on the full sample of patients in ENACT-2, said these data showed a similar impact. “In the more difficult-to-treat subsets of patients studied here, TYSABRI helped patients with moderate to severe CD achieve and maintain a considerably improved QOL as measured by the IBDQ and the SF-36 as compared with placebo,” Dr. Feagan said.
“TYSABRI is an important treatment option for patients with this debilitating disease who have failed anti-TNFα therapies,” stated Elan President Carlos V. Paya, MD, PhD.
“Quality of life is an important measure of how CD patients feel in their day-to-day lives,” said Michael Panzara, MD, MPH, vice president, chief medical officer of neurology, Biogen Idec.
Feagan BG, Sandborn WJ, Hass S, et al. (2007). Health-Related Quality of Life During Natalizumab Maintenance Therapy for Crohn’s Disease. Am J Gastroenterol, 102:2737–2746. doi: 10.1111/j.1572-0241.2007.01508.x
About ENCORE and ENACT-2
Data from the ENCORE trial showed that TYSABRI induced response and remission among patients with moderately to severely active CD, 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.
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.
About Crohn's Disease (CD)
An estimated 500,000 people in the United States have CD, a chronic and progressive inflammatory disease of the gastrointestinal tract, which commonly affects both men and women. CD 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 CD. Many patients fail to respond to current therapies, including biological therapies such as agents that inhibit tumor necrosis factor alpha (TNFα). Due to this failure of current therapies in CD, therapies that have alternate biological targets provide patients and physicians with therapeutic options.
The disease usually causes diarrhea and cramping 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.