Eptinezumab in episodic migraine: A randomized, double-blind, placebo-controlled study (PROMISE-1)

Abstract

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

Methods: The PRevention Of Migraine via Intravenous ALD403 Safety and Efficacy-1 (PROMISE-1) study was a phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Adults with episodic migraine were randomized to eptinezumab 30 mg, 100 mg, 300 mg, or placebo for up to four intravenous (IV) doses administered every 12 weeks. The primary endpoint was change from baseline in monthly migraine days (MMDs) over weeks 1-12.

Results: A total of 888 patients received treatment across 84 study sites. Mean MMDs at baseline was ∼8.6 across treatment groups. Eptinezumab 100 mg and 300 mg met the primary endpoint, significantly reducing MMDs across weeks 1-12 compared with placebo (30 mg, -4.0; 100 mg, -3.9, p = 0.0182; 300 mg, -4.3; placebo, -3.2, p = 0.0001). Treatment-emergent adverse events were reported by 58.4% (30 mg), 63.2% (100 mg), 57.6% (300 mg), and 59.5% (placebo) of patients. Treatment-emergent adverse events reported by ≥2% of eptinezumab-treated patients at an incidence greater than placebo included: upper respiratory tract infection (30 mg, 11.4%; 100 mg, 9.9%; 300 mg, 10.3%; placebo, 7.2%), and fatigue (30 mg, 2.3%; 100 mg, 3.6%; 300 mg, 3.6%; placebo, <1%).

Conclusion: Eptinezumab (100 mg or 300 mg) significantly reduced migraine frequency, was well tolerated, and had an acceptable safety profile when used for the preventive treatment of migraine in adults with episodic migraine. ClinicalTrials.gov identifier: NCT02559895.

Keywords: ALD403; Eptinezumab; efficacy; episodic migraine; safety.

Figure 1.

Decision rule for dose levels (primary and key secondary endpoints). ^aStatistical significance must have been met to proceed to the next test within 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. ICF: informed consent form; PK: pharmacokinetics.

Figure 3.

Primary endpoint: Change from baseline to week 12 in mean monthly migraine days (full analysis population). ^aNot statistically significant per the testing hierarchy; unadjusted p-value presented.

Figure 4.

Key secondary endpoints: (a) ≥75% migraine responder rates and (b) ≥50% migraine responder rates (full analysis population). ^aNot statistically significant per the testing hierarchy; unadjusted p-value presented.