Experimental drugs may stop migraines before they start

Competing teams of researchers are closing in on a new class of drugs that can prevent chronic migraines by interrupting the chain of events thought to create the headaches.

The drugs target a biochemical called calcitonin gene-related peptide (CGRP). The results from phase 2 clinical trials show that these drugs can effectively prevent migraine in a substantial portion of headache sufferers, according to the studies.

"It's very exciting, because this would be a form of prevention that might not have a lot of side effects and would be highly effective for people who have not had good treatment," said Dr. Thomas Ward, a professor of neurology at Geisel School of Medicine at Dartmouth in New Hampshire. "The hope is these drugs will be clean, reduce the number of headaches people get, and won't carry a lot of baggage."

Findings from these studies were to be presented this week at the annual meeting of the American Headache Society, in Washington D.C.

Researchers have known for more than two decades that CGRP plays an important role in migraine headaches, said Dr. Peter Goadsby, chair of the scientific program of the American Headache Society's annual meeting and chief of the University of California, San Francisco Headache Center.

The body uses CGRP to control the opening of blood vessels, and it also is thought to play a role in the transmission of pain signals, Ward said.

"The last step in the pathway we think to setting off headache is this substance called CGRP," Ward said. "This material is released by nerves, and when released it causes inflammation in the nervous system."

Headache drugs called triptans currently are used to stop migraines in progress, and they work by blocking CGRP, Ward said. But until now, researchers have been unable to come up with a way to prevent onset of migraines by targeting CGRP.

Traditional pharmaceuticals have not panned out in heading off migraines by blocking CGRP, Goadsby said. CGRP is widely used throughout the body, and blocking its function entirely can cause serious side effects in a number of organs.

This latest class of drugs reduces levels of CGRP through the use of monoclonal antibodies -- laboratory-created antibodies that can be engineered to target any substance in the body.

These are the first drugs specifically developed for prevention of migraines, Goadsby said. Up to now, doctors have repurposed drugs developed for other health problems -- for example, high blood pressure -- to treat migraine.

"This is the first time that migraine patients will get migraine drugs for prevention," Goadsby said.

Four drug manufacturers -- Alder Pharmaceuticals, Amgen, Eli Lilly and Company, and Teva Pharmaceuticals -- currently are testing their own versions of CGRP monoclonal antibodies. Goadsby is helping test Amgen's CGRP monoclonal antibody.

A drug that effectively prevents migraine could prove lucrative. More than 36 million Americans have migraines, more than have asthma or diabetes combined, according to the American Headache Society. About 4 million have chronic migraine, experiencing more than 15 migraine days a month, according to the society.

In results presented at the American Headache Society meeting:

• Teva reported that its drug achieved a significant reduction in the number of headache hours after one week, with more than half of patients in each arm experiencing a 50 percent or greater reduction in headache frequency.
• Amgen reported that its drug reduced the number of migraine days by 50 percent in about half the treated patients after 12 weeks.
• Lilly showed that its drug could help prevent migraine headaches, compared against placebo.

Alder Pharmaceuticals didn't present any new findings at the meeting, but has previously published promising phase 2 study results, according to an American Headache Society news release.

The drugs are all administered via injection, said Goadsby.

If the drugs prove successful, migraine patients could get a monthly injection to prevent some or all of their headaches, he said.

"They clearly work for a substantial proportion of people," Goadsby said. "About half of patients will get 50 percent response, and a fifth will get 100 percent response."

CGRP monoclonal antibodies so far have shown limited side effects, with only 3 percent of patients dropping out of trials due to adverse events, Ward said.

However, there is some concern about the long-term use of these drugs, given how CGRP is used throughout the body for many different purposes, he said.

"CGRP is so widespread, it's hard to tell whether it could cause consequences throughout the body," Ward said.

The data and conclusions of research presented at medical meetings should be viewed as preliminary until published in a peer-reviewed journal.