New Migraine Abortive Shows Promise without Vasoconstriction

by Teri Robert, MyMigraineConnection Lead Expert

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Phase II study data on MK-0974, an investigational oral calcitonin gene-related peptide (CGRP) receptor antagonist showed:

  • MK-0974 significantly improved Migraine pain relief two hours after dosing (compared to placebo), and the relief was sustained through 24 hours.
  • MK-0974 was generally well tolerated.
  • In addition to pain relief, MK-0974 successfully relieved other Migraine symptoms including nausea, phonophobia (sensitivity to sound), and photophobia (sensitivity to light).

MK-0974 is Merck’s investigational medicine in Phase III clinical development for the acute treatment of Migraine in adults. Phase III Trials are usually the last trials conducted before FDA approval and marketing of a drug. If approved, it could be the first in a new class of Migraine treatments since the approval of the first triptan in 1991. The triptans (Imitrex, Maxalt, Zomig, Amerge, Relpax, Axert, and Frova) have changed the way millions of Migraineurs treat their attacks. Unlike pain medications, triptans are Migraine abortives. They work to actually stop the Migrainous process.
Tony Ho, M.D., senior director of Clinical Neurosciences, Merck Research Laboratories, talked with me at the American Headache Society (AHS) 49th Annual Scientific Meeting. He commented,

“…MK-0974 has a novel new mechanism for relief. Nearly 70% get pain relief at two hours. The results are excellent for sustained relief at 24 hours. The adverse even rate is similar to placebo.”
In an earlier statement, Dr. Ho said,

“The findings of this early-stage trial demonstrated the therapeutic potential of MK-0974 for the acute treatment of Migraines. Larger clinical trials, such as those now underway, will provide more insight into the efficacy and safety profile of MK-0974.”

How MK-0974 works

MK-0974 is an antagonist of the receptor for CGRP, a primary neuropeptide involved in the pathophysiology of Migraine. CGRP and its receptors are found in areas of the central and peripheral nervous system that are important for the transmission of pain impulses. MK-0974 blocks the binding of CGRP to receptors within these areas and thereby is believed to inhibit the transmission of pain signals that lead to Migraine attacks.
Dr. Alan Rapoport, clinical professor of Neurology at the David Geffen School of Medicine at UCLA in Los Angeles, founder and director-emeritus of the New England Center for Headache, and a clinical investigator for the Phase II study commented,

“These results provide additional evidence of the potential benefit of CGRP receptor antagonists as a new and promising class of Migraine therapies.”


The results on MK-0974 thus far look quite promising. Not only is the success rate impressive, it’s equally impressive to see adverse events no more significant with the medication than with placebo.
The development of a new class of Migraine abortives is welcome news to Migraineurs. Triptans, the most widely used abortives, are generally not recommended for patients with a history of or significant risk factors for heart disease or stroke. They are also generally not recommended for basilar-type Migraine or hemiplegic Migraine. I asked Dr. Ho if MK-0974 would be safe for those Migraineurs. He told me that it’s just not possible to predict such issues until the trials are complete. He did comment that MK-0974 is not a vasoconstrictor. Given that, I believe the results of the remaining tests of MK-0974 definitely bear extra watching for those who cannot take triptans because of the vasoconstriction.
If the testing goes as expected, MK-0974 could be available in 2009.



News Release: “Merck’s Investigational Migraine Treatment MK-0974 Significantly Improved Migraine Pain on Several Efficacy Measures in a Phase II Study.” Merck. Chicago. June 7, 2007.
Interview: Teri Robert with Tony Ho., M.D., senior director of Clinical Neurosciences, Merck Research Laboratories. June 7, 2007.


Last updated June 7, 2007.

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