Two novel agents for migraine prevention could be on the horizon

Abstract

Two investigational monoclonal antibodies that target either the calcitonin gene-related peptide (CGRP) receptor or CGRP itself were effective for preventive treatment of migraines compared with placebo, according to results from two recent studies. Erenumab, a fully human monoclonal antibody that inhibits the CGRP receptor, was assessed in a Phase III trial involving 955 adult patients with episodic migraine. Patients with at least 4 but fewer than 15 migraine days per month and fewer than 15 headache days per month on average were randomized to either erenumab 70 mg (n = 317), erenumab 140 mg (n = 319), or placebo (n = 319) given as monthly S.C. injections for 6 months. At month 6, use of erenumab at either dose significantly reduced the mean number of migraine days per month compared with placebo (−3.2 d for 70 mg and −3.7 d for 140 mg vs. −1.8 d for placebo; P < 0.001 for both comparisons). Also, significantly more patients in the two active treatment groups had a 50% or greater reduction in mean number of migraine days per month and used less acute migraine-specific medication compared with those in the placebo group. Physical impairment scores and everyday activities scores were also significantly improved in the erenumab groups compared with placebo. The frequency of adverse events was similar across the three treatment groups (55.5%–63.0%). Fremanezumab, a humanized monoclonal antibody that targets CGRP itself, was assessed in a Phase III trial involving 1,130 adult patients with chronic migraine. Eligible patients included those with a headache of any duration or severity on 15 or more days per month and migraine on 8 or more days per month. Patients were randomized to a single quarterly S.C. dose of fremanezumab 675 mg (n = 376), monthly fremanezumab (675 mg at baseline and 225 mg at weeks 4 and 8, n = 379), or placebo (n = 375). After 12 weeks, use of fremanezumab resulted in a significant reduction in mean number of headache days per month compared with placebo (−4.3 d for quarterly fremanezumab and −4.6 d for monthly vs. −2.5 d for placebo; P < 0.001 for both comparisons). Also, significantly more patients in the active treatment arms had at least a 50% reduction in mean number of headache days per month compared with placebo. The frequency of adverse events was similar across the three treatment groups (64%–71%), and injection-site reactions occurred in approximately one-quarter to one-third of the patients. Efficacy of both novel agents was modest, but these agents worked rapidly, and some patients became completely headache free. Four different CGRP antibodies are currently in development (i.e., erenumab, eptinezumab, fremanezumab, and galcanezumab), and clinical data are needed to differentiate these agents and determine if their effects are sustained after discontinuation or if long-term treatment is needed. Data from two trials showed that novel investigational injectable agents are effective in reducing the frequency of episodic and chronic migraines. Patients with a history of migraines should speak to their health care provider about alternative treatment options that may be appropriate for them.