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In this randomised, double-blind, placebo-controlled, exploratory, proof-of-concept phase 2 trial, patients aged 18–55 years with five to 14 migraine days per 28-day period were randomly assigned (1:1) via an interactive web response system to receive an intravenous dose of ALD403 1000 mg or placebo. Site investigators, patients, and the sponsor were masked to treatment allocation during the study. The primary objective was to assess safety at 12 weeks after infusion. The primary efficacy endpoint was the change from baseline to weeks 5–8 in the frequency of migraine days, as recorded in patient electronic diaries. Patients were followed up until 24 weeks for exploratory safety and efficacy analyses. Safety and efficacy analyses were done by intention to treat. This study is registered with ClinicalTrials.gov, NCT01772524.Read More →

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In this randomized, double-blind, placebo-controlled, multicenter trial (ClinicalTrials.gov NCT00797667), patients experiencing 3–14 migraine days during a 4-week baseline were randomized to telcagepant 140 mg, telcagepant 280 mg, or placebo twice daily for 12 weeks. Efficacy was assessed by mean monthly headache days and migraine/probable migraine days (headache plus ≥1 associated symptom). The trial was terminated following a recommendation from the Safety Monitoring Board due to hepatotoxicity concerns. At termination, the planned 660 patients had been randomized, 656 had been treated with ≥1 dose of study medication, and 14 had completed the trial. Read More →

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In The Lancet Neurology, David Dodick and colleagues1 introduce monoclonal antibodies into the specialty of primary headache therapy. They report findings from a randomised, placebo-controlled, double-blind, phase 2 clinical trial of LY2951742, a neutralising humanised monoclonal antibody against calcitonin gene-related peptide (CGRP), for migraine prevention. The subcutaneous administration of LY2951742 once every 2 weeks reduced the mean number of migraine headache days per 28-day period between baseline and weeks 9–12 (primary endpoint; least-squares mean difference −1·2, 90% CI −1·9 to −0·6; p=0·0030) in a population with a high frequency of migraine; the antibody was also superior to placebo in several secondary endpoints after 12 weeks of treatment.Read More →

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In June, Teva of Petach Tikva, Israel, paid $200 million in cash and $625 million in future milestones to acquire Labrys Biologics of San Mateo, California. The Israeli drug maker wanted to get its hands on LBR-101, the biotech’s preventive treatment for migraines and its only asset. LBR-101, a humanized monoclonal a…Read More →

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Calcitonin gene-related peptide (CGRP) is a well-studied neuropeptide of relevance for migraine pathophysiology. Jugular levels of CGRP are increased during migraine attacks, and intravenous CGRP administration induces migraine-like headache in most individuals with migraine. Several CGRP receptor antagonists (CGRP-RAs) were shown to be effective for the acute treatment of migraine, validating the target for the treatment of migraine. However, for a number of reasons, including issues of liver toxicity with chronic use, the development of CGRP-RAs has yet to produce a viable clinical therapeutic. Read More →

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Migraine is a primary brain disorder resulting from altered modulation of normal sensory stimuli and trigeminal nerve dysfunction. The second edition of the International Classification of Headache Disorders (ICHD-2) defines seven subtypes of migraine. Migraine treatment can be acute or preventive. New targeted therapies include 5-HT1F receptor agonists, calcitonin gene-related peptide (CGRP) antagonists, nitric oxide synthetase inhibitors, and ion channel antagonists. A recent development is the creation of antibodies to CGRP and its receptor for migraine prevention.Read More →

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The neuropeptide calcitonin gene-related peptide (CGRP) has long been postulated to play an integral role in the pathophysiology of migraine. While clinical findings are consistent with such a role, the specific pathogenic mechanisms of CGRP in migraine have remained speculative until recently. Through advances in molecular neuroscience, the pathogenic mechanisms of CGRP in migraine have begun to be elucidated. This paper discusses the hypothesized role of CGRP in migraine and reviews recent findings on the molecular mechanisms of this neuropeptide in migraine pathophysiology. Studies in cultured trigeminal neurons demonstrate that CGRP is released from trigeminal ganglia cells, that CGRP transcription is increased under conditions mimicking neurogenic inflammation, that migraine pharmacotherapies can both reduce CGRP release and inhibit CGRP transcription, and that tumor necrosis factor-α (TNF-α), an endogenous inflammatory mediator implicated in migraine, can stimulate CGRP transcription. Read More →