Telcagepant proven as a safe and effective migraine treatment in phase III trial

November 24, 2008

Telcagepant 300 mg is effective as an acute treatment for migraine with efficacy comparable to that of zolmitriptan 5 mg, a widely used migraine treatment, but with fewer associated adverse effects. These are the conclusions of an Article published Online first and in and upcoming edition of The Lancet, written by Dr Tony Ho, Merck Research Laboratories, North Wales, Philadelphia, USA, and colleagues.

Migraine is a common source of pain and disability, and currently triptans, such as zolmitriptan, are standard treatments. Generally well tolerated, triptans can be associated with side-effects such as dizziness, tingling and numbness of the skin, throat tightness, and chest discomfort (not thought to be of cardiac origin in most patients), which can cause some patients to discontinue or change treatment. Furthermore, because of potential vasoconstrictor effects, triptans are contraindicated in patients with substantial underlying cardiovascular disease, uncontrolled high blood pressure, and certain migraine subtypes. Hence, new treatments for migraine are needed for people who do not respond well to current therapies or who are at substantial risk of cardiovascular disease. Calcitonin gene-related peptide (CGRP) is a neuropeptide thought to have a key role in the pathophysiology of migraine. CGRP concentrations circulating in the brain may be increased during a migraine attack and CGRP given intravenously triggers a migraine-like headache in people who have migraines. Antagonism of these receptors has thus become an important target for new migraine treatments, and, furthermore, since CGRP antagonists do not seem to have direct vasoconstricting (blood vessel narrowing) properties, they might be free of the cardiovascular concerns associated with triptans.

This randomised controlled phase III study analysed 1380 patients from 81 sites in the USA and Europe. All patients had moderate or severe migraine as defined by International Headache Society criteria. Patients received telcagepant 150 mg (333 patients) or 300 mg (354), zolmitriptan (345), or placebo (348). Telcagepant 300 mg was more effective than placebo for freedom from pain (27% of patients vs 10%) , pain relief (55% vs 28%), and absences of phonophobia (58% vs 37%) photophobia (51% vs 29%) , and nausea (65% vs 55%) . Efficacy of telcagepant 300 mg and zolmitriptan 5 mg were much the same, and both were more effective than telcagepant 150 mg. Adverse events were recorded for 31% taking telcagepant 150 mg, 37% taking telcagepant 300 mg, 51% taking zolmitriptan 5 mg, and 32% taking placebo.

The authors say: "One potential benefit of the new CGRP receptor antagonist class of acute migraine treatments is the absence of vasoconstriction, a liability of the triptans, which may allow for the safe administration of telcagepant in patients with migraine with cardiovascular disease. However, such patients were excluded from the present study because of the contraindication for zolmitriptan, and further studies are necessary to determine the safety of telcagepant in patients with cardiovascular disease. Additional studies are also necessary to assess the long-term efficacy and safety profile of telcagepant in patients treating more than one migraine attack."

They conclude: "Telcagepant 300 mg is effective as an acute treatment for migraine with efficacy comparable to that of zolmitriptan 5 mg, but with fewer associated adverse effects."

In an accompanying Comment, Dr Lars Edvinsson, Lund University, University Hospital, Sweden, says: "Telcagepant is associated with a lower incidence of side-effects than the triptan. This result marks a new era in migraine therapy. However, the remaining issue is to understand the site of action of the CGRP-receptor antagonists."
-end-
Dr Tony Ho, Merck Research Laboratories, North Wales, Philadelphia, USA
T) +1-267-305-7957
E) tony_ho@merck.com

Dr Lars Edvinsson, Lund University, University Hospital, Sweden
T) +46 (0)703 271484 / +46 46 171484
E) lars.edvinsson@med.lu.se

Full Article and Comment: http://press.thelancet.com/migrainemerckfinal.pdf

Lancet

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