Efficacy and safety of eptinezumab in patients with chronic migraine: PROMISE-2

Richard B Lipton, Peter J Goadsby, Jeff Smith, Barbara A Schaeffler, David M Biondi, Joe Hirman, Susan Pederson, Brent Allan, Roger Cady, Richard B Lipton, Peter J Goadsby, Jeff Smith, Barbara A Schaeffler, David M Biondi, Joe Hirman, Susan Pederson, Brent Allan, Roger Cady

Abstract

Objective: To evaluate the efficacy and safety of eptinezumab, a humanized anti-calcitonin gene-related peptide monoclonal antibody, in the preventive treatment of chronic migraine (CM).

Methods: The Prevention of Migraine via Intravenous ALD403 Safety and Efficacy-2 (PROMISE-2) study was a phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Adults with CM were randomly assigned to receive IV eptinezumab 100 mg, eptinezumab 300 mg, or placebo administered on day 0 and week 12. The primary endpoint was change from baseline in mean monthly migraine days (MMDs) over weeks 1 to 12.

Results: Among treated participants (n = 1,072), baseline mean number of MMDs was ≈16.1 across groups. Treatment with eptinezumab 100 and 300 mg was associated with significant reductions in MMDs across weeks 1 to 12 compared with placebo (placebo -5.6, 100 mg -7.7, p < 0.0001 vs placebo; 300 mg -8.2, p < 0.0001 vs placebo). Treatment-emergent adverse events (TEAEs) were reported by 43.5% (100 mg), 52.0% (300 mg), and 46.7% (placebo) of patients. Nasopharyngitis was the only TEAE reported for >2% of eptinezumab-treated patients at an incidence of >2% over placebo; it occurred in the 300 mg eptinezumab arm (eptinezumab 9.4%, placebo 6.0%).

Conclusion: In patients with CM, eptinezumab 100 and 300 mg was associated with a significant reduction in MMDs from the day after IV administration through week 12, was well tolerated, and demonstrated an acceptable safety profile.

Classification of evidence: This study provides Class I evidence that for patients with CM, a single dose of eptinezumab reduces MMDs over 12 weeks of treatment.

Clinicaltrialsgov identifier: NCT02974153.

Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Figures

Figure 1. Decision rule for dose levels…
Figure 1. Decision rule for dose levels (primary and key secondary endpoints)
HIT-6 = Headache Impact Test-6; MMD = monthly migraine day. aStatistical significance must have been met to proceed to the next step with each series. bTo proceed to the next series, all tests in the previous series must have shown a statistically significant difference from placebo.
Figure 2. Patient disposition
Figure 2. Patient disposition
Figure 3. Primary endpoint: Change from baseline…
Figure 3. Primary endpoint: Change from baseline to week 12 in mean monthly migraine days (full analysis population)
Figure 4. Key secondary endpoints (full analysis…
Figure 4. Key secondary endpoints (full analysis population)
(A) ≥75% migraine responder rates, (B) ≥50% migraine responder rates, and (C) patients with migraine on day 1 and during weeks 1 to 4.

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