Offering new data for Antegren against Crohn's disease, Biogen Idec Inc. said it will file for approval in the European Union but is conducting another study in the U.S. before seeking approval here.
"We plan to share these data with the FDA, and we've initiated the additional Phase III induction trial, which is enrolling patients right now," said Amy Brockelman, spokeswoman for Cambridge, Mass.-based Biogen Idec.
Meanwhile, plans remain on track to file in the second quarter for U.S. and European approval of Antegren, an alpha-4 integrin inhibitor, as a multiple sclerosis therapy.
Biogen Idec's stock (NASDAQ:BIIB) moved up 1 cent Wednesday to close at $59.22.
Last summer, Antegren (natalizumab), which is partnered with Dublin, Ireland-based Elan Corp. plc, missed its primary endpoint in a three-month induction trial called ENACT-1 (Evaluation of Natalizumab in Active Crohn's Disease Therapy-1). Specifically, the drug failed to get a 70 point decrease in the Crohn's Disease Activity Index at week 10.
But new data from a trial called ENACT-2, disclosed at the Digestive Disease Week in New Orleans, showed 61 percent of the patients from that trial got benefit after six months of continued therapy. What's more, the study in 339 Antegren responders found that patients on chronic corticosteroid therapy were able to withdraw from it and maintain their Antegren response.
Evan Beckman, vice president of medical research for Biogen Idec, said the findings affirm what investigators suspected: Since the drug's effects in ENACT-1 appeared consistent with satisfying Phase II results, a high placebo rate was to blame for the missed endpoint.
"That's one of many interpretations, but that was our bias, and now we've confirmed there was true drug effect," Beckman told BioWorld Today from the DDW meeting. "The difference between those who came off the drug and those who stayed on is very large."
ENACT-2 re-randomized participants from the first study to get 300 mg of Antegren (168 patients) or placebo (171 patients), both dosed monthly for 12 months. The primary endpoints of maintained response and remission were evaluated through six months. Of the 168 treated patients, 103 continued to respond, compared with 29 percent, or 49 patients, on placebo. Also, 44 percent of Antegren patients maintained clinical remission vs. 26 percent on placebo.
On the corticosteroids front, 54 percent of Antegren-treated patients taking them in the first trial and re-randomized for the second were able to withdraw from corticosteroids and maintain response and disease remission, compared to 25 percent of patients on placebo.
"Physicians rate that very high," said Beckman, a rheumatologist. "We use [corticosteroids] to treat rheumatoid arthritis, but the gastrointestinal community really doesn't like them, especially for the long term. It's very difficult to wean patients off, and there are many side effects" - some of which (such as bone loss, high blood pressure and Type II diabetes) sneak up on patients, who are feeling better and don't want to quit the drugs.
"There are nuisance side effects also," Beckman said, pointing to insomnia and psychological disturbances.
Researchers said they found no notable differences in the rate of adverse events, serious or non-serious, between treatment groups in ENACT-2. The most common drug-related adverse events in either treatment group were headache, fatigue and nausea.
The humanized monoclonal antibody Antegren is the first alpha-4 antagonist in the new selective adhesion molecule (SAM) inhibitor class, and works by inhibiting the migration of immune cells into chronically inflamed tissue. A second induction trial in Crohn's will improve upon the first effort, Beckman said.
"It's a totally different protocol," he said. "One piece is that we will be enrolling patients who have high [C-reactive protein, or CRP] at baseline. Interestingly, CRP or another laboratory marker called a sedimentation rate - both are cheap, fast and available to any physician, in a hospital or not - are already used in other diseases, but not previously in Crohn's. This doesn't mean in clinical practice everybody's going to check CRP before prescribing the drug, but it helps in the study design."
In Crohn's generally, study design is a troublesome matter, Beckman said.
"It's not entirely peculiar to Crohn's," he said. "In RA, they're seeing a little bit of it. But it has reached crescendo proportions in the GI/Crohn's world. Last year, at this same meeting, that was all the buzz."
Sorting patients might be difficult because "biologics are more comfortable for people to use," Beckman said, so the trials enroll less-ill patients. Or the trial participants might not have inflammation as the true cause of their abdominal pain.
Diary cards on which patients report how they feel are commonly used to evaluate trial participants. "There are some laboratory markers and physical findings, but these don't drive the score," he said, adding that some patients might not even have Crohn's but irritable bowel syndrome, a condition "people don't totally understand, but it's not the active inflammation" likely causing pain.
With the FDA's go-ahead, Biogen Idec and Elan plan to use one-year Phase III data in Antegren against multiple sclerosis as the basis for the regulatory bid here. A Phase II trial with Antegren in rheumatoid arthritis also is under way. (See BioWorld Today, Feb. 19, 2004.)
In separate news, partner Elan said it completed the sale of commercialization rights for the migraine drug Frova (frovatriptan), bought for about $55 million by Vernalis plc, of Winnersh, UK. The deal includes $5 million up front, with more payments by the end of 2005. Elan ended its co-promotion deal with UCB Pharma Inc. and will pay about $10 million to the Brussels, Belgium-based company. (See BioWorld Today, April 2, 2004.)