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. 2024 Feb;13(1):85-105.
doi: 10.1007/s40120-023-00562-w. Epub 2023 Nov 10.

Comparing the Efficacy and Safety of Galcanezumab Versus Rimegepant for Prevention of Episodic Migraine: Results from a Randomized, Controlled Clinical Trial

Todd J Schwedt  1 , Tina M Myers Oakes  2 , James M Martinez  3 , Bert B Vargas  3 , Hitendra Pandey  3 , Eric M Pearlman  3 , Diane R Richardson  3 , Oralee J Varnado  3 , Michael Cobas Meyer  3 , Peter J Goadsby  4   5
Affiliations

Comparing the Efficacy and Safety of Galcanezumab Versus Rimegepant for Prevention of Episodic Migraine: Results from a Randomized, Controlled Clinical Trial

Todd J Schwedt et al. Neurol Ther. 2024 Feb.

Abstract

Introduction: There have been no prior trials directly comparing the efficacy of different calcitonin gene-related peptide (CGRP) antagonists for migraine prevention. Reported are the results from the first head-to-head study of two CGRP antagonists, galcanezumab (monoclonal antibody) versus rimegepant (gepant), for the prevention of episodic migraine.

Methods: In this 3-month, double-blind, double-dummy study, participants were randomized (1:1) to subcutaneous (SC) galcanezumab 120 mg per month (after a 240 mg loading dose) and a placebo oral disintegrating tablet (ODT) every other day (q.o.d.) or to rimegepant 75 mg ODT q.o.d. and a monthly SC placebo. The primary endpoint was the proportion of participants with a ≥ 50% reduction in migraine headache days per month from baseline across the 3-month double-blind treatment period. Key secondary endpoints were overall mean change from baseline in: migraine headache days per month across 3 months and at month 3, 2, and 1; migraine headache days per month with acute migraine medication use; Migraine-Specific Quality of Life Questionnaire Role Function-Restrictive domain score at month 3; and a ≥ 75% and 100% reduction from baseline in migraine headache days per month across 3 months.

Results: Of 580 randomized participants (galcanezumab: 287, rimegepant: 293; mean age: 42 years), 83% were female and 81% Caucasian. Galcanezumab was not superior to rimegepant in achieving a ≥ 50% reduction from baseline in migraine headache days per month (62% versus 61% respectively; P = 0.70). Given the pre-specified multiple testing procedure, key secondary endpoints cannot be considered statistically significant. Overall, treatment-emergent adverse events were reported by 21% of participants, with no significant differences between study intervention groups.

Conclusions: Galcanezumab was not superior to rimegepant for the primary endpoint; however, both interventions demonstrated efficacy as preventive treatments in participants with episodic migraine. The efficacy and safety profiles observed in galcanezumab-treated participants were consistent with previous studies.

Trial registration: ClinTrials.gov-NCT05127486 (I5Q-MC-CGBD).

Keywords: CGRP antagonist; Calcitonin gene-related peptide (CGRP); Clinical study; Comparative efficacy; Galcanezumab; Gepant; Head-to-head; Migraine; Prevention; Rimegepant.

Plain language summary

Galcanezumab and rimegepant are preventive treatments for episodic migraine. The goal of this study was to compare the efficacy of galcanezumab and rimegepant in reducing the number of monthly migraine headaches and to determine if galcanezumab was better than rimegepant. The study provides important information to doctors and their patients when making treatment decisions.People with episodic migraine were assigned to the galcanezumab (given as an injection under the skin) or rimegepant (given as a tablet that dissolves in the mouth) group and treated for 3 months. The doctor and the patient did not know which group they were assigned to, and to keep it unknown to both, people in the galcanezumab group got an injection with real medicine and a fake tablet, and people in the rimegepant group got a tablet with real medicine and a fake injection. The researchers wanted to know how many people in each group had at least a 50% reduction in their monthly migraine headaches.Of the 580 people in the study, 287 were assigned to galcanezumab and 293 to rimegepant. In both groups, most were female and white. After 3 months of treatment, 62% of the people in the galcanezumab group and 61% of people in the rimegepant group had at least a 50% reduction in monthly migraine headaches. Both treatments were effective, but galcanezumab was not better than rimegepant. About 20% of the people in each treatment group had a side effect from the medication, and most were mild or moderate in severity.

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Conflict of interest statement

Todd Schwedt has received compensation for consulting for Abbvie, Allergan, Axsome, Collegium, Eli Lilly, Linpharma, Lundbeck, Satsuma, and Theranica; research funding from Amgen, Mayo Clinic, National Institutes of Health, Patient Centered Outcomes Research Institute, SPARK Neuro, and the United States Department of Defense; stock options in Aural Analytics and Nocira; and is on the board of directors for the American Headache Society and the American Migraine Foundation. Peter Goadsby reports, over the last 36 months, a grant from Celgene; personal fees from Aeon Biopharma, Abbvie, Amgen, CoolTech LLC, Dr Reddys, Eli Lilly and Company, Epalex, Lundbeck, Novartis, Pfizer, Praxis, Sanofi, Satsuma, Shiratronics, Teva Pharmaceuticals, and Tremeau; personal fees for advice through Gerson Lehrman Group, Guidepoint, SAI Med Partners, and Vector Metric; fees for educational materials from CME Outfitters; publishing royalties or fees from Massachusetts Medical Society, Oxford University Press, UptoDate, and Wolters Kluwer; and a patent for magnetic stimulation for headache (no. WO2016090333 A1) assigned to eNeura without fee. James Martinez, Michael Cobas Meyer, Tina Myers Oakes, Hitendra Pandey, Eric Pearlman, Diane Richardson, Bert Vargas, and Oralee Varnado are employees of Eli Lilly and Company, Indianapolis, IN, USA.

Figures

Fig. 1
Fig. 1
Study design. All participants received SC injections using a prefilled syringe and ODT. Visits 1, 2, 3 (randomization) and 6 were conducted in the office. Visits 4 and 5 were telephone visits. At visit 3, participants randomized to galcanezumab 120 mg received a 240-mg loading dose (two injections) and one ODT placebo, and participants randomized to rimegepant received one rimegepant 75 mg ODT and two placebo injections. ePRO electronic patient-reported outcome, ODT orally disintegrating tablet, QOD every other day, SC subcutaneous, SP study period
Fig. 2
Fig. 2
Participant study disposition
See this image and copyright information in PMC

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