NEW YORK (Reuters Health) – MK-0974, a novel oral antagonist to calcitonin gene-related peptide (CGRP) receptor, is effective for the acute treatment of migraine, according to a report in the April 15th issue of Neurology.

“MK-0974 utilizes a new mechanism to provide pain relief that is unique from currently available anti-migraine therapies,” Dr. Tony W. Ho from Merck Research Laboratories, North Wales, Pennsylvania told Reuters Health. “We also believe the mechanism has the potential to provide a differentiated cardiovascular profile over available therapies.”

Dr. Ho and colleagues evaluated the clinical profile of various doses of MK-0974 in the acute treatment of migraine in 420 adults with moderate or severe migraine attacks.

None of the doses up to 200 mg showed evidence of effectiveness, the investigators report, but doses of 300 mg, 400 mg, and 600 mg were significantly better than placebo at providing pain relief at 2 hours.

Higher doses were also effective in providing pain freedom at 2 hours, 24 hour sustained pain relief, and 24 hour sustained pain freedom, the report indicates, and in reducing associated symptoms of photophobia and phonophobia at 2 hours, use of optional second dose at 2 hours, and use of rescue medication by 4 hours.

Treatment was well tolerated, with a similar incidence of adverse experiences in the treatment and placebo groups.

“The findings from this early study support and extend the previous proof-of-concept findings for CGRP receptor antagonists,” Dr. Ho said. “In general, the development of a CGRP receptor antagonist, which can be taken orally, represents a key advance in migraine therapy. If approved, MK-0974 may be the first in a new class of migraine treatments since the approval of the first triptan in 1991.”

“The study raises many more issues than it answers, as with any good project,” writes Dr. Peter J. Goadsby from University of California, San Francisco, in a related editorial. “The placebo response was high and this illustrates the importance of well controlled designs. The dose response was not as clear-cut as one might like, but I suspect this is an artifact of the adaptive design.”

The editorial concludes: “The development of CGRP receptor antagonists for migraine, indeed, any therapeutic development for migraine, is for the benefit of many we see in clinical practice whose lives remain blighted by an utterly reversible problem.”

Neurology 2008;70:1304-1312,1300-1301.