Calcitonin gene-related peptide (CGRP) receptor antagonist MK-0974 holds promise as a migraine abortive, according to Phase II study results that will be presented at the American Headache Society‘s annual meeting this week.
The drug works by blocking CGRP, a brain chemical that is important for transmitting pain signals during a migraine. It does not appear to contrict blood vessels, as triptans do, so people who can’t use triptans may be able to use MK-0974 as an abortive. Researchers hope that it will have fewer side effects and safety concerns than triptans do.
The American Headache Society’s press release on the study follows.
New Migraine Drug Holds Promise for Headache Sufferers: First Class of Migraine Medication Since the Triptans
CHICAGO – An innovative drug appears to treat migraines in a majority of people, potentially ushering in a new era for the treatment of the painful and disabling headaches, suggests early research being presented at the 49th Annual Scientific Meeting of the American Headache Society.
The study is the first presentation of a drug called MK-0974, which belongs to a potential new class of drugs, known as calcitonin gene-related peptide (CGRP) receptor antagonists.
Fifteen years ago, the advent of triptan medication revolutionized migraine treatment by stopping the headaches and related symptoms, rather than just providing pain relief. However, triptans don’t work for about a third of the estimated 28 million people with migraines and because they constrict blood vessels, they cannot be used in patients who have had a heart attack or stroke and should be used with caution by those who are at risk.
“The real excitement is that this drug has a different mechanism of action from the triptans, and the hope is that it will have fewer side effects and safety concerns,” said Alan M. Rapoport, M.D., clinical professor of neurology at the David Geffen School of Medicine at UCLA, in Los Angeles, and a co-author of a study on the drug being presented at the Society’s meeting.
The new drug works by blocking CGRP, a brain chemical that is important for transmitting pain signals during a migraine attack. Unlike the triptans, research has shown that the new drug does not appear to constrict blood vessels.
“Because we know that the CGRP level is elevated during a migraine attack, and that if you give CGRP intravenously, you can cause a migraine-like headache, we’ve been studying what would happen if you block the CGRP,” said Tony Ho, M.D., senior director of clinical neuroscience at Merck & Co., Whitehouse Station, N.J. “Our hope is that this drug potentially can have a significant impact for migraine patients as an additional treatment choice.”
The new drug has not been approved by the Food and Drug Administration (FDA). Results from the Phase II study being presented at the Society meeting are an early step in the development process.
The randomized, double-blind, placebo-controlled study tested safety and effectiveness of MK-0974 and involved a total of 330 people who suffered one to six migraines a month. Study patients kept a diary to assess: pain relief two hours after taking the medication, pain freedom two hours after taking the medication, and freedom from pain 24 hours later.
More than two-thirds (68 percent) of those who took the 300 mg dose of the new drug had pain relief two hours after the dose, compared to 69.5 percent of those who took the FDA approved triptan called rizatriptan and 46 percent who took a placebo, or dummy pill. Nearly half (45.2 percent) of those who took the new drug were free of pain after two hours, compared to 33.4 percent who took rizatriptan [Maxalt] and 14.3 percent who took the placebo.
More than a third (39.6 percent) were free of pain 24 hours after taking the new drug, compared to 18.4 percent who took rizatriptan and 11 percent who took the placebo. Common side effects included nausea, dizziness and sleepiness.
“These early results are very promising,” said Dr. Ho. “There’s potential for the new drug to be superior to the triptans 24 hours after the medication is taken, but this needs to be confirmed in a larger trial.”
“There’s good reason to believe that at least some people would respond to this drug, even if they did not respond to the triptans,” said Dr. Rapoport, who also is the cofounder and director emeritus of The New England Center for Headache, in Stamford, Conn. “Also, additional data suggest that this drug gets into the blood stream fairly quickly and may stay in the blood stream longer than several of the triptans.”
In addition to Drs. Rapoport and Ho, other authors of the paper being presented at the meeting are: Lisa Mannix, M.D., Xiaoyin Fan, Ph.D., Chris Assaid, Ph.D., Christine Furtek, M.S. and Chris Jones, M.S.