Therapeutic novelties in migraine: new drugs, new hope?

Abstract

Background: In the past decade, migraine research has identified novel drug targets. In this review, we discuss recent data on emerging anti-migraine therapies.

Main body: The development of ditans, gepants and anti-calcitonin gene-related peptide monoclonal antibodies for the treatment of migraine is one of the greatest advances in the migraine field. Lasmiditan, rimegepant and ubrogepant will extend our therapeutic armamentarium for managing acute migraine attacks when triptans are not effective or contraindicated due to cardiovascular disorders. The monoclonal antibodies are migraine specific prophylactic drugs with high responder rates and favorable adverse event profiles. Furthermore, they offer convenient treatment regimens of 4- or 12-week intervals.

Conclusion: Collectively, novel migraine therapies represent a major progress in migraine treatment and will undoubtedly transform headache medicine.

Keywords: Adverse event; Antibody; Ditan; Efficacy; Gepant; Migraine; Randomized clinical trial; Tolerability.

Fig. 1

Overview of patients (%) achieving 2-h pain freedom in lasmiditan phase III clinical trials with different doses. A darker bar indicates a higher dose. *vs. placebo, p < 0.001

Fig. 2

Overview of the therapeutic gain* in 2-h pain freedom with lasmiditan. A darker bar indicates a higher dose. *Therapeutic gain is defined as the difference between percentage of responders in active group compared to percentage of responders in placebo group

Fig. 3

Overview of the therapeutic novelties targeting the calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating polypeptide/pituitary adenylate cyclase 1 (PACAP/PAC₁) pathways developed for migraine

Fig. 4

Overview of patients (%) achieving 2-h pain freedom in rimegepant phase III clinical trials. *Study 301; vs. placebo, p < 0.003. Study 302; vs. placebo, p < 0.001

Fig. 5

Overview of patients (%) achieving 2-h pain freedom in ubrogepant phase III clinical trials. *ACHIEVE I; 50 mg vs. placebo, p = 0.0023; 100 mg vs. placebo, p = 0.0003. ACHIEVE II; 25 mg vs. placebo, p = 0.0285; 50 mg vs. placebo, p = 0.0129

Fig. 6

Overview of the therapeutic gain* in 2-h pain freedom with gepants. A darker bar indicates a higher dose. *Therapeutic gain is defined as the difference between percentage of responders in active group compared to percentage of responders in placebo group

Fig. 7

Overview of patients (%) achieving > 50% reduction in migraine days in phase III clinical trials with erenumab. A darker bar indicates a higher dose. *ARISE; 70 mg vs. placebo, p = 0.010. STRIVE; 70 mg vs. placebo, p < 0.001; 140 mg vs. placebo, p < 0.001

Fig. 8

Overview of patients (%) achieving > 50% reduction in migraine days in phase III clinical trials with eptinezumab. A darker bar indicates a higher dose. *PROMISE I; 100 mg vs. placebo, p = 0.0085; 300 mg vs. placebo, p = 0.0001. PROMISE II; 100 mg vs. placebo, p < 0.0001; 300 mg vs. placebo, p < 0.0001

Fig. 9

Overview of patients (%) achieving > 50% reduction in migraine days in phase III clinical trials with fremanezumab. A darker bar indicates a higher dose. *NCT02629861 (left); 225 mg vs. placebo, p < 0.001; 675 mg vs. placebo, p < 0.001. NCT02629861 (right); 225 mg vs. placebo, p < 0.001; 675 mg vs. placebo, p < 0.001

Fig. 10

Overview of patients (%) achieving > 50% reduction in migraine days in phase III clinical trials with galcanezumab. A darker bar indicates a higher dose. *EVOLVE-1; 120 mg vs. placebo, p < 0.001; 240 mg vs. placebo, p < 0.001. EVOLVE-2; 120 mg vs. placebo, p < 0.001; 240 mg vs. placebo, p < 0.001

Fig. 11

Overview of the therapeutic gain* in percentage of patients with > 50% reduction in migraine days with anti-calcitonin gene-related peptide monoclonal antibodies. A darker bar indicates a higher dose. *Therapeutic gain is defined as the difference between percentage of patients in active group compared to percentage of patients in placebo group