Antegren® Phase III Clinical Trial Completed
The Phase III trial to determine if Antegren® (natalizumab) induces remission in moderate to severe Crohn's disease, known as ENACT-1, is now completed. Elan Corporation announced on Thursday, July 24 that the trial did not meet the primary endpoint of response, which was defined as a 70 point drop in the Crohn's Disease Activity Index (CDAI) at week 10. This result appears to be due to a larger than expected placebo response rate, a phenomenon seen in other Crohn's disease trials over the past few years.
While complete data from the trial will be presented to the scientific and medical communities at medical meetings later this year, the trial did suggest that natalizumab and its unique mechanism of action have an important effect on inflammation. Indeed, even though the endpoint was not met at week 10, statistically significant response and remission endpoints were seen at week 12.
The study also found a significant effect on multiple markers of inflammation found in the blood, such as C-reactive protein and platelets, in the natalizumab treated patients as compared to placebo. Nearly 72% of the 905 patients enrolled in the trial demonstrated evidence of active inflammation, and these patients had statistically significant clinical responses and remission rates at week 10 compared to placebo.
Results of the Phase II trial were published earlier this year in the New England Journal of Medicine. The Phase II trial was the first to demonstrate that by selectively inhibiting immune cells from leaving the bloodstream, and preventing them from migrating into tissue such as the intestines, inflammation could be reduced. Natalizumab is the first alpha-4 antagonist in a new class of drugs known as SAM (selective adhesion molecule) inhibitors.
"Clearly, further studies are needed to determine natalizumab's true efficacy in Crohn's disease," said Richard Blumberg, M.D., the Chair of CCFA's National Scientific Advisory Committee. Dr. Blumberg is an Associate Professor of Medicine, Harvard Medical School, and Chief of the Gastroenterology Division at the Brigham and Women's Hospital. "The data regarding the effect on the multiple markers of inflammation may indicate a definite impact on biological activity in Crohn's patients. This is the first major example that targeting this particular part of the immune system can be successful in IBD, and opens the way for a wide variety of other target agents."
Natalizumab is also being tested in two Phase III studies in multiple sclerosis. One trial tests natalizumab alone, and the second tests it in combination with another drug known as interferon beta-1a. Data is not expected from these trials until the end of 2004.
Elan, in cooperation with Biogen, have stated they are committed to the continued development of Antegren® for both Crohn's disease and multiple sclerosis. A trial to determine if natalizumab is effective in maintaining remission in Crohn's disease, known as ENACT-2 is still ongoing. (Enrollment for this trial is completed).
For more information on natalizumab, you can view CCFA's Webcast, "Leading Edge Developments in the Diagnosis and Treatment of IBD," or visit www.elan.com.
Date Posted: July 24, 2003 |
