The investigators noted that these data provide robust and promising evidence that eptinezumab is associated with a rapid preventive effect in chronic migraine that is sustained for 3 months after a single infusion.
David W. Dodick, MD
Results of a randomized phase 2b clinical trial suggest that eptinezumab is both effective and well-tolerated in the preventive treatment of chronic migraine, and according to the investigators, justifies the phase 3 clinical trials in its development for migraine prevention.
In a cohort of 495 treated patients, the ≥75% responder rates to the intravenous anti-calcitonin gene-related peptide (CGRP) monoclonal antibody was an average of 29.9% across the 4 doses measured in the trial—300, 100, 30, and 10 mg. Led by David W. Dodick, MD, professor of neurology, Mayo Clinic College of Medicine, the investigators noted that the results for the 3 highest doses (mean ≥75% responder rate, 30.9%) was statistically favorable compared to placebo for the key secondary end points.
“These results provide preliminary, yet robust and promising evidence that eptinezumab administered by IV infusion to patients with [chronic migraine] is associated with a rapid migraine preventive effect that is sustained for 3 months after a single dose and is associated with acceptable safety and favorable tolerability profiles,” Dodick and colleagues wrote.
In total, 616 patients with chronic migraine were enrolled, with a mean onset at ≤35 years and a history of the condition for ≥1 year. They were randomized 1:1:1:1:1 to a single infusion of 300- (n = 121), 100- (n = 122), 30- (n = 122), or 10-mg (n = 130) eptinezumab, or placebo (n = 121). The treatment period was 12 weeks, and the screening period was 28 days, during which patients must have had ≥15 headache days, including ≥8 migraine days, with ≥5 migraine attacks.
The ≥75% responder rates were 33.3% (P
= .033), 31.4% (P
= .072), 28.2% (P
= .201), and 26.8% (P
= .294), respectively, for the eptinezumab 300, 100, 30, and 10 mg groups compared to 20.7% for placebo. The ≥50% response rates were 57.0% (P
= .013), 55.1% (P
= .029), 55.6% (P
= .024), and 43.9% (P
= .621), respectively, compared with 40.5% for placebo.
Additionally, a post hoc analysis of one of the key secondary end points—change in Headache Impact Test (HIT-6) score—showed that baseline scores were meaningfully changed (a ≥5-point reduction) in the 300 mg (–10 points), 100 mg (–6.9 points), 30 mg (–6.5 points), and 10 mg (–6.5 points). In comparison, the placebo group experienced a 5.8-point reduction. Baseline HIT-6 scores were placebo: 63.4 (standard deviation [SD], 4.6), 300 mg: 64.5 (SD, 4.4), 100 mg: 64.4 (SD, 5.2), 30 mg: 63.9 (SD, 5.2), and 10 mg, 64.7 (SD, 5.2).
“[This] analysis suggests that a clinically meaningful reduction of migraine activity can be achieved as early as day 1 post-infusion,” Dodick et al. detailed, noting that the percentages of patients who had migraine 1 day post-infusion for the 300- and 100-mg groups were 26.3% and 29.3%, respectively, compared to 48.7% for placebo. On average, 59.1% of those in the 300-mg group, 60.4% of those in the 100-mg group, and 58.7% of those in the placebo group experienced a migraine on any given day during the 28-day baseline period.
“This represents, for the eptinezumab groups, a > 50% reduction in the likelihood of a migraine day in the 24 hours post-infusion compared with baseline,” the investigators wrote.
Likewise, a prespecified analysis of the percentage of those whose migraine had severe impact showed massive reductions for the 300 mg (baseline, 90.3%; week 12, 29.9%) and 100 mg (baseline, 86.4%; week 12, 43.0%) groups compared to placebo (baseline, 79.3%; week 12, 50.9%).
Average monthly migraine days were reduced by 8.2 (16.5 to 8.3; P
= .003), 7.6 (16.9 to 9.3; P
= .018), 7.9 (16.2 to 8.3; P
= .005), and 6.7 (16.4 to 9.7; P
= .180) for the eptinezumab 300-, 100-, 30-, and 10-mg groups, respectively. In comparison, the placebo group experienced a reduction of 5.5 (16.4 to 10.9) monthly migraine days. As well, Dodick et al. wrote that the change in migraine/headache hours and the average percentages of severe migraines favored eptinezumab versus placebo.
The safety profile was considered tolerable, with 68 (56.2%), 77 (63.6%), 70 (57.5%), 56 (45.9%), and 74 (56.9%) patients in the placebo, 300-, 100-, 30-, and 10-mg groups experiencing an adverse event (AE). In total, 16 patients reported serious AEs, though none were deemed to be related to eptinezumab.
“These results, combined with the lack of dose titration, quarterly administration, and favorable side effect profile, have the potential to improve adherence and long-term outcomes compared with currently available preventive treatments,” Dodick and colleagues wrote.
Dodick DW, Lipton RB, Silberstein S, et al. Eptinezumab for prevention of chronic migraine: A randomized phase 2b clinical trial. Cephalalgia. 2019;39(9):1075-1085. doi: 10.1177/0333102419858355.