Elan Corporation plc and Biogen Idec have submitted a Marketing Authorisation Application (MAA) to the European Medicines Agency for the approval of Antegren (natalizumab) as a treatment for Crohn's disease. Additionally, the companies presented new 12-month data from the phase III maintenance trial, Enact-2 (Evaluation of Natalizumab As Continuous Therapy-2), at the United European Gastroenterology Week meeting in Prague, Czech Republic, and these data were included in the filing.
According to a release, data from Enact-2 showed a sustained and clinically significant response throughout 12 months of extended natalizumab infusion therapy, confirming findings in patients who had previously shown a sustained response throughout six months (data presented at Digestive Disease Week in May, 2004). Maintenance of response was defined by a Crohn's Disease Activity Index (CDAI) score of less than 220, and less than 70-point increase from baseline, in the absence of rescue intervention throughout the study. Response was maintained by 54 per cent (90/168) of patients treated with natalizumab compared to 20 percent (34/170) of those treated with placebo. In addition, 39 per cent (51/130) of patients on natalizumab maintained clinical remission during the study period, versus 15 per cent (18/120) of those on placebo.
By the end of month 12, 49 per cent (33/67) of natalizumab-treated patients who had previously been treated with corticosteroids were able to withdraw from steroid therapy compared to 20 per cent (15/76) of placebo-treated patients. No notable difference in the overall rates of side effects between natalizumab and placebo treatment groups was observed through month 12. The safety profile seen in this trial was similar to that seen in previous natalizumab trials, the release added.
"This filing and the presentation of 12-month data from the Enact-2 study represent important milestones in our development of natalizumab as a treatment for Crohn's disease, and we are committed to working closely with the European regulators to facilitate a thorough review of our submission and the supporting data," Lars Ekman, executive vice president and president, Research and Development, Elan said adding, "We believe natalizumab can be an important therapy in this underserved patient population."
"These findings suggest that natalizumab may sustain a significant level of efficacy and safety in the treatment of Crohn's disease," said Burt Adelman, executive vice president, Development, Biogen Idec. "These data also reinforce natalizumab's potential across a range of immune-mediated diseases," he added.
Natalizumab, a humanized monoclonal antibody, is the first alpha-4 antagonist in the new selective adhesion molecule (SAM) inhibitor class. The drug is designed to inhibit the migration of immune cells into tissues where they may cause or maintain inflammation.
Elan and Biogen Idec are collaborating equally on the development of natalizumab in multiple sclerosis, Crohn's disease, and rheumatoid arthritis. Based on one-year phase III data in MS, the companies have submitted applications for drug approval in the US and Europe. The FDA has designated natalizumab for Priority Review and Accelerated Approval for the treatment of multiple sclerosis. In addition, a phase II trial for rheumatoid arthritis is underway.
Approximately one million people worldwide 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 diarrhoea, crampy abdominal pain, often fever, and at times rectal bleeding. Loss of appetite and subsequent 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), malnutrition and decreased growth rate in children.