Drug May Offer New Avenue to Fight Migraine

First one that doesn't constrict blood vessels

WEDNESDAY, March 10, 2004 (HealthDayNews) -- A trial drug that blocks the action of a chemical released during a migraine attack may represent a potent new treatment for migraine sufferers.

The drug, now called BIBN 4096 BS, was effective in treating migraines up to six hours after they started and would be the first migraine medication that does not constrict blood vessels.

"It's a landmark study," says Dr. Vincent Martin, co-director of the Cincinnati Headache Center and an associate professor of medicine at the University of Cincinnati College of Medicine. "It's a completely different way of treating migraine."

It's also an early study -- and one that may well be only a precusor to any definitive new treatment, according to other experts.

"This medication is likely multiple years away from being brought to market, so it's not going to change the lives of patients with migraines immediately," says Dr. Robert Shapiro, assistant professor of neurology at the college of medicine at the University of Vermont in Burlington.

Dr. Stewart Tepper, director of the New England Center for Headache in Stamford, Conn., says, "If this is going to be important for migraine, it is as a proof of concept. They've shown that if you can block the CGRP receptor, you can alleviate a migraine. ... They have a proof of concept. It works. It fits all of the theories."

Adds Tepper, a clinical assistant professor of neurology at Yale University School of Medicine in New Haven, "My understanding is that the company has been unable to come up with a pill form."

It will be important whether a pill form of the drug can be developed that is equally effective as the intravenous version used in the study.

"The key thing is being able to find an oral formulation," Martin says. "Just because intravenous works doesn't mean the pill form will. It's still a way off from being something the typical migraine patient will take."

Other experts anticipate that the difference could be evident more in the usual side effects than in how well such a drug would work.

Triptans, a class of drug used for migraines, constrict blood vessels and are therefore contraindicated in people with cardiovascular conditions.

"[The drug] may not be that much more effective, but for those who can't take triptans, [it] might be very useful," says Paul Durham, author of a perspective article accompanying the study, which appears in the March 11 issue of the New England Journal of Medicine.

"That's the major leap," adds Durham, an assistant professor of cell biology at Southwest Missouri State University in Springfield.

According to the accompanying perspective article, migraines are considered to be a neurovascular disorder because they involve interplays between the nerves in the brain and blood vessels. Specifically, it appears that, during a migraine attack, the trigeminal nerve, which is the main sensory nerve, becomes activated and releases CGRP, calcitonin gene-related peptide, which in turn dilates the blood vessels of the brain. Because the vessels are surrounded by nerves, every time a vessel expands or contracts, it is perceived as pain, Martin explains.

It seemed logical, then, that something that blocked CGRP would also help relieve a migraine. That something turned out to be BIBN 4096 BS, a compound produced by Boehringer Ingelheim Pharmaceuticals in Germany.

In laboratory and animal studies, the compound did block the effects of CGRP. So an international, multi-center trial was set up to see if the compound would work in humans.

Researchers enrolled 126 migraine patients, all of whom had a history of one to six migraines per month for the preceding six months. The age of the participants ranged from 18 to 65.

The researchers first experimented with doses, all given intravenously over a period of 10 minutes, to determine the lowest dose that was still superior to a placebo. The minimal effective dose turned out to be 2.5 milligrams, which had a 66 percent response rate vs. 27 percent for the placebo. Overall, people taking any dose of BIBN 4096 BS had a 60 percent response rate.

BIBN 4096 BS (which researchers expect to be renamed soon) was also better than the placebo in helping the participants be pain-free after two hours, sustaining the rate of response over 24 hours, and the rate of recurrence (19 percent for the 2.5-mg group vs. 46 percent in the placebo group) as well as improving the levels of nausea and sensitivity to light and sound. The effect kicked in after 30 minutes and increased over the next few hours.

There were no serious side effects of BIBN 4906 BS, but there were instances of paresthesia, a burning or prickling sensation.

More information

For more on migraines, visit the National Institute of Neurological Disorders and Stroke or the National Headache Foundation.

SOURCES: Vincent Martin, M.D., associate professor of medicine, University of Cincinnati College of Medicine, and co-director, Cincinnati Headache Center; Paul Durham, Ph.D., assistant professor of cell biology, Southwest Missouri State University, Springfield; Robert Shapiro, M.D., Ph.D., assistant professor of neurology, College of Medicine, University of Vermont, Burlington; Stewart Tepper, M.D., director, New England Center for Headache, Stamford, Conn., and clinical assistant professor of neurology, Yale University School of Medicine, New Haven; March 11, 2004, New England Journal of Medicine
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