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

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.

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 3. Primary endpoint: Change from baseline to week 12 in mean monthly migraine days (full analysis population)

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.