Evaluation of Galcanezumab for the Prevention of Episodic Migraine

Abstract

IMPORTANCE Migraine is a disabling neurological disease characterized by severe headache attacks. Treatment options reduce migraine frequency for many patients, but adverse effects lead to discontinuation in many patients. OBJECTIVE To demonstrate that galcanezumab is superior to placebo in the prevention of episodic migraine with or without aura. DESIGN, SETTING, AND PARTICIPANTS The EVOLVE-1 (Evaluation of LY2951742 in the Prevention of Episodic Migraine 1) trial was a double-blind, randomized, placebo-controlled (January 11, 2016, to March 22, 2017) trial comparing galcanezumab (120 mg and 240 mg) vs placebo. Patients received treatments once monthly for 6 months (subcutaneous injection via prefilled syringe) and were followed up for 5 months after their last injection. It was a multicenter, clinic-based study involving 90 sites in North America. Participants in the study were adults (aged 18 to 65 years) with at least a 1-year history of migraine, 4 to 14 migraine headache days per month and a mean of at least 2 migraine attacks per month within the past 3 months, and were diagnosed prior to age 50 years. During the study, no other preventive medications were allowed. A total of 1671 patients were assessed; 809 did not meet study entry or baseline criteria, and 858 were included in the intent-to-treat population. INTERVENTIONS Patients were randomized (2:1:1) to monthly placebo, galcanezumab, 120 mg, and galcanezumab, 240 mg. MAIN OUTCOMES AND MEASURES The primary outcome was overall mean change from baseline in the number of monthly migraine headache days during the treatment period. Secondary measures included at least 50%, at least 75%, and 100% reduction in monthly migraine headache days, migraine headache days with acute medication use, and scores from the Migraine-Specific Quality of Life questionnaire, Patient Global Impression of Severity, and Migraine Disability Assessment. Treatment-emergent adverse events and serious adverse events were reported. RESULTS Of the 1671 patients assessed, 858 (mean age, 40.7 years; 718 women [83.7%]) met study entry criteria and received at least 1 dose of investigational product. The primary objective was met for both galcanezumab doses; treatment with galcanezumab significantly reduced monthly migraine headache days (both P < .001) by 4.7 days (120 mg) and 4.6 days (240 mg) compared with placebo (2.8 days). All key secondary objectives were also significant after multiplicity adjustment. There were no meaningful differences between 120-mg and 240-mg doses of galcanezumab on measures of efficacy. Completion rate during treatment was high (81.9%; n = 718), and the incidence of discontinuation owing to adverse events was less than 5% across all treatment groups. CONCLUSIONS AND RELEVANCE Galcanezumab 120-mg and 240-mg monthly injections provided clinical benefits and improved functioning. The incidence rate of adverse events was low, demonstrating the favorable tolerability profile of galcanezumab.

Rapid Onset of Effect of Galcanezumab for the Prevention of Episodic Migraine: Analysis of the EVOLVE Studies

“…11 Galcanezumab is a humanized monoclonal antibody that potently and selectively binds to the CGRP ligand 12,13 and is approved for the preventive treatment of migraine in adults. 19,20 There were also no clinically meaningful differences between the 2 galcanezumab doses with respect to safety profiles. [19][20][21] In EVOLVE-1 (NCT02614183) and EVOLVE-2 (NCT02614196), patients with episodic migraine treated with monthly galcanezumab of 120-mg or 240-mg doses had a greater decrease from baseline than did placebo-treated patients in the average number of MHDs per month over the 6 , with no statistically significant differences between the 2 galcanezumab doses in either study.…”

“…10 A recent study evaluated cycling of preventive migraine medications from a claims database and found that for patients with episodic and chronic migraine, more than 75% of patients switched or discontinued their initial preventive treatment within 12 months, leading to increased healthcare resource utilization and cost. [19][20][21] In EVOLVE-1 (NCT02614183) and EVOLVE-2 (NCT02614196), patients with episodic migraine treated with monthly galcanezumab of 120-mg or 240-mg doses had a greater decrease from baseline than did placebo-treated patients in the average number of MHDs per month over the 6 , with no statistically significant differences between the 2 galcanezumab doses in either study. 14,15 The efficacy, safety, and tolerability of galcanezumab for migraine prevention have been established in 2 Phase 2 studies 16-18 and 3 Phase 3 studies.…”

100% Response Rate to Galcanezumab in Patients With Episodic Migraine: A Post Hoc Analysis of the Results From Phase 3, Randomized, Double‐Blind, Placebo‐Controlled EVOLVE‐1 and EVOLVE‐2 Studies

“…The full description of patient disposition is provided in previous publications 17, 18. Table 1 presents the baseline demographics and the disease characteristics for the 2 galcanezumab dose groups and the placebo group.…”

Novel Medications for the Treatment of Migraine

“…76,77 Patients were randomized to either galcanezumab 240 mg monthly, 120 mg monthly following a loading dose of 240 mg, or placebo. 76,77 Patients were randomized to either galcanezumab 240 mg monthly, 120 mg monthly following a loading dose of 240 mg, or placebo.…”

“…76,77 Patients were randomized to either galcanezumab 240 mg monthly, 120 mg monthly following a loading dose of 240 mg, or placebo. 76 EVOLVE-2 reported MDD reduction of −2.0 days (120 mg) and −1.9 days (240 mg). 76,77 Further studies also found a significant reduction in acute medication use.…”