Effect of Different Doses of Galcanezumab vs Placebo for Episodic Migraine Prevention

Abstract

IMPORTANCE Galcanezumab (LY2951742), a monoclonal antibody against calcitonin gene-related peptide (CGRP), is one of a novel class of new medicines for migraine prevention. OBJECTIVE To assess whether at least 1 dose of galcanezumab was superior to placebo for episodic migraine prevention. DESIGN, SETTING, AND PARTICIPANTS A randomized clinical trial was conducted in the United States (July 7, 2014, to August 19, 2015) in clinics of 37 licensed physicians with a specialty including, but not limited to, psychiatry, neurology, internal medicine, and primary care. Subcutaneous injections of galcanezumab, 5, 50, 120, or 300 mg, or placebo were given monthly during the 3-month treatment period. A total of 936 patients were assessed; 526 did not meet study entry or baseline criteria and 410 patients were randomly assigned to receive placebo or galcanezumab. Analyses were conducted on an intent-to-treat population, which included all patients who were randomized and received at least 1 dose of study drug. INTERVENTIONS Short-term migraine treatments were allowed as needed except for opioids or barbiturates. MAIN OUTCOMES AND MEASURES To determine if at least 1 of the 4 doses of galcanezumab tested was superior to placebo for migraine prevention measured by the mean change from baseline in the number of migraine headache days 9 weeks to 12 weeks after randomization. RESULTS Of the 936 patients assessed, 410 met entry criteria (aged 18-65 years with 4-14 migraine headache days per month and migraine onset prior to age 50 years) and were randomized to receive placebo or galcanezumab. For the primary end point, galcanezumab, 120 mg, significantly reduced migraine headache days compared with placebo (99.6% posterior probability −4.8 days; 90% BCI, −5.4 to −4.2 days vs 95% superiority threshold [Bayesian analysis] −3.7 days; 90% BCI, −4.1 to −3.2 days). Adverse events reported by 5% or more of patients in at least 1 galcanezumab dose group and more frequently than placebo included injection-site pain, upper respiratory tract infection, nasopharyngitis, dysmenorrhea, and nausea. CONCLUSIONS AND RELEVANCE Monthly subcutaneous injections of galcanezumab, both 120 mg and 300 mg, demonstrated efficacy (repeated-measures analysis) for the preventive treatment of migraine and support further development in larger phase 3 studies. All dosages were safe and well tolerated for the preventive treatment of episodic migraine. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT02163993

The American Headache Society Position Statement On Integrating New Migraine Treatments Into Clinical Practice

“…These biologic agents have demonstrated efficacy, safety, and tolerability for the preventive treatment of episodic and chronic migraine in phase 2 and phase 3 randomized, placebo-controlled trials, 43,44,[47][48][49][50][51][52][53][54][55] and they represent the first mechanism-based and disease-specific class of preventive treatment that was designed, developed, and made available for migraine since methysergide was Food and Drug Administration approved in 1962. These biologic agents have demonstrated efficacy, safety, and tolerability for the preventive treatment of episodic and chronic migraine in phase 2 and phase 3 randomized, placebo-controlled trials, 43,44,[47][48][49][50][51][52][53][54][55] and they represent the first mechanism-based and disease-specific class of preventive treatment that was designed, developed, and made available for migraine since methysergide was Food and Drug Administration approved in 1962.…”

“…56 At the time of this writing, erenumab, fremanezumab, and galcanezumab are available for use in migraine prevention, and filing is expected for eptinezumab in 2019. 43,44,[47][48][49][50][51][52][53][54][55] Conclusions about long-term safety will require real-world clinical experience from use in large, heterogeneous patient populations. None of these agents requires dose titration.…”

Prevalence of Migraine in the Elderly: A Narrated Review

“…Tricyclic antidepressants, beta blockers, sodium valproate, topiramate, lisinopril, candesartan, calcium channel blockers, onabotulinum toxin injections, CGRP antagonists or CGRP receptor antagonists are prescription alternatives currently approved for use as migraine prevention [51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66]. However, yet again it is important to use these medications with caution in the elderly -ideally at low doses initially and slow gradual increase [67].…”

CGRP, Amylin, Immunology, and Headache Medicine

“…The rabbit appears to be an appropriate maternal-fetal model, as all IgG classes appear to cross with greater efficiency than in humans. 112 Additionally, no adverse parental, reproductive, or developmental effects were observed in any study at any dose with exposures 14-fold greater than human exposure levels. 111 In the CGRP therapeutics database in the public domain, there is a single report of a male birth of a galcanezumab-treated father on 300 mg with ankyloglossia, a birth defect that decreases mobility of the tip of the tongue, associated with a pathologically short, thick lingual frenulum.…”