Despite a failed trial last year, Antegren now has garnered some positive Phase III data, meeting its primary endpoint by maintaining a response in Crohn's disease patients.
Partners Biogen Idec Inc. and Elan Corp. plc could file for regulatory approval in the U.S. and Europe sometime this year.
"Not only were the study results highly statistically significant," said Lars Ekman, executive vice president and president of research development at Dublin, Ireland-based Elan, "but more important, there was a significant treatment of greater than 30 percent difference in favor of Antegren in patients taking the drug, compared to those taking placebo. To say the least, we are very encouraged by these results."
The Phase III study, known as ENACT-2 (Evaluation of Natalizumab as Continuous Therapy-2), enrolled 428 patients, each receiving a total of 12 infusions of either 300 mg of the drug or placebo over one year. The patients enrolled in the trial had responded to therapy in the ENACT-1 trial conducted over a three-month period in patients with very active Crohn's disease.
The primary endpoint of maintenance of response was defined by a sustained Crohn's Disease Activity Index (CDAI) score of less than 220, as well as no use of rescue intervention throughout six months. Researchers observed no notable difference in side effects between the two groups. Side effects included headaches, nausea and abdominal pain.
The companies plan to give a detailed report of the results at a medical meeting in the first half of this year, following its meetings with FDA authorities.
"This is a very exciting day for this collaboration between Biogen Idec and Elan, and just as importantly, for patients with Crohn's disease," said Burt Adelman, executive vice president of development at Cambridge, Mass.-based Biogen Idec, during a conference call conducted with Elan. "We're very excited about these results and feel that, as the community of physicians who treat these patients learns more about these results, they'll see that they're very clinically meaningful."
Without speaking with the FDA concerning the data, company officials declined to provide a timeline for regulatory filing of Antegren, but analysts have estimated a Crohn's filing could come as early as this summer.
"It's an important product for [Biogen Idec] because both Avonex and Rituxan have slowing growth," said Mike King, managing director at Banc of America Securities LLC in New York. "To add any dimension to growth, the companies need new products."
Biogen Idec's Avonex was approved for multiple sclerosis in 1996, while Rituxan was approved in 1997 for non-Hodgkin's lymphoma.
King declined to give a financial outlook for Antegren, but did say that Centocor Inc.'s Remicade, which was approved for Crohn's disease in 1998, brought in $500 million in sales in 2002. Remicade, he said, had a more stringent efficacy criteria for approval than Antegren did.
"From my own standpoint," he told BioWorld Today, "I would have been more impressed if they used a CDAI of under 150 rather than 220."
Analysts from Leerink Swann & Co. said much the same thing in a research note, stating that physician consultants "are less enthusiastic" about reductions in CDAI scores than they are about the achievement of remission, which is defined as a CDAI score of below 150.
King suggested that getting approval of Antegren as a maintenance therapy for Crohn's disease could be a strategic move for Biogen Idec, allowing the company to later file a supplemental application for multiple sclerosis. Two Phase III trials of Antegren for MS are under way with more than 2,000 patients enrolled. The trials are blinded two-year studies, and the company has not released results.
The Leerink Swann note stated that Antegren's largest commercial opportunity is probably as a treatment for MS. "Given that many MS patients fail beta-interferon therapy," the note said, "and there remains the potential that Antegren could function in a complementary manner with those drugs, we believe the revenue opportunity could be sizable."
In July 2003, Biogen Inc. and Elan released disappointing Phase III data for ENACT-1, showing that Antegren did not meet its primary endpoint of a response - a 70-point decrease in the CDAI at week 10. In that study, Antegren was being looked at as an induction therapy. (See BioWorld Today, July 25, 2003.)
The latest Phase III trial is for the use of Antegren as a maintenance therapy. Some analysts questioned whether an unapproved induction agent would be accepted as a maintenance therapy.
Adelman said the two kinds of therapy are very distinct. "Patients with Crohn's disease require induction therapy when their disease is active and they require maintenance therapy, just as importantly, to keep them from reverting to active disease," he said.
People with active disease, he explained, have a significant amount of inflammatory cell infiltrate in their gut, which located there by crossing the bloodstream. While a therapeutic strategy for induction would look at what's going on in the wall of the gut, a maintenance strategy would aim to keep new lymphocytes from getting into the gut.
The drugs currently available for Crohn's disease might not be the best options for long-term maintenance of the disease, Adelman said. "Antegren continues to have an outstanding safety profile in long-term therapy," Adelman said. "To date, we have given this drug to over 2,700 patients and have continued to see a very acceptable adverse event profile suggesting this is an excellent drug for long-term maintenance."
Antegren (natalizumab) is a humanized monoclonal antibody that is the first alpha-4 antagonist in the new selective adhesion-molecule inhibitor class. It is designed to selectively inhibit immune cells from leaving the bloodstream and to prevent the cells from migrating into chronically inflamed tissue, being the gastrointestinal tract in Crohn's disease, the brain in MS and the joints in rheumatoid arthritis.
Biogen Idec's stock (NASDAQ:BIIB) rose 57 cents Thursday to close at $43.40.