A long-term extension of the DELIVER phase 3b clinical trial has demonstrated that eptinezumab, a CGRP-targeted monoclonal antibody, maintains significant efficacy in reducing migraine frequency and impact for up to 18 months in patients with treatment-resistant migraine. The findings, presented at the International Headache Congress 2023, provide crucial evidence for sustained benefit in a challenging patient population.
Sustained Efficacy in Treatment-Resistant Population
The DELIVER trial enrolled 892 adults with migraine who had documented evidence of 2-4 previous preventive treatment failures in the prior 10 years. Of the 865 patients who completed the initial 24-week placebo-controlled period, 782 (90.4%) completed an additional 48 weeks of follow-up, demonstrating excellent long-term tolerability.
Dr. Messoud Ashina from the Danish Headache Centre at Rigshospitalet Glostrup reported that eptinezumab "continued to suppress migraine at 18 months through multiple measures of control and across multiple relevant subgroups." The study population represented a particularly challenging group, with nearly all patients (99%) having at least one treatment failure due to lack of response, and nearly 40% having experienced at least 3 prior drug failures.
Robust Response Rates Maintained
The extension study revealed impressive and sustained response rates. By the end of 18 months of follow-up, more than 60% of patients achieved at least a 50% reduction in monthly migraine days (MMDs) from baseline, and more than 30% achieved at least a 75% reduction. These response rates were maintained across both the 100 mg and 300 mg dosing groups.
For patients initially randomized to placebo who were switched to eptinezumab during the extension phase, the onset of benefit was rapid. When evaluated three weeks after switching, the mean reduction in MMDs was 5.8 days for the 100 mg dose and 7.2 days for the 300 mg dose, confirming the drug's rapid onset of action.
Significant Reduction in Acute Medication Use
A particularly important finding was the sustained reduction in acute migraine medication use. At baseline, patients across treatment groups were using acute migraine medications for approximately 11 days per month, generally above the ICHD-3 threshold for acute medication overuse. Following eptinezumab initiation, patients used approximately 5 fewer days per month of acute migraine medications compared to baseline, bringing the average to below thresholds for medication overuse.
Dr. Anna Gryglas-Dworak from the MIGRE Polish Migraine Center reported that these reductions were highly statistically significant (P<0.0001) whether evaluated for the full dataset or for those who entered the study with medication overuse. The mean acute headache medication use in the 100 mg eptinezumab group was reduced at 72 weeks from baseline by 4.7 days in the full dataset and by 7.0 days in the medication overuse subgroup.
Improved Quality of Life and Functional Outcomes
The study demonstrated comprehensive improvements in patient-reported outcomes beyond migraine frequency reduction. Mean HIT-6 total scores, which indicated severe headache-related life impact at baseline (66.0-66.6), were reduced by 11.0 to 14.0 points by the end of the extension. This represents a shift from severe impact to moderate impact for participants.
Dr. Peter J. Goadsby from King's College London presented data showing that patients experienced significant improvements in work productivity. Based on the migraine-specific Work Productivity Impairment questionnaire (WPAI:M), patients had significantly larger reductions in absenteeism (P<0.05), work productivity loss (P<0.001), and activity impairment (P<0.001) compared to placebo. These improvements were documented at the first assessment at 4 weeks and persisted throughout the study.
Consistent Efficacy Across Subgroups
Post-hoc analyses revealed that eptinezumab's efficacy was independent of the class of prior failed migraine therapy. Dr. Patricia Pozo-Rosich from Vall d'Hebron University Hospital reported that whether patients had previously failed topiramate, beta blockers, amitriptyline, or flunarizine, the mean reduction in MMDs ranged between 4.8 and 5.0 days at 12 weeks for the 100 mg dose and 5.5 to 6.0 days for the 300 mg group across all drug classes.
Safety Profile Remains Favorable
The long-term safety profile of eptinezumab remained consistent with previous studies. Treatment-emergent adverse events were reported with similar frequency across groups, with the most commonly reported events being COVID-19, nasopharyngitis, and upper respiratory tract infection. The proportions of patients with serious adverse events, treatment-emergent adverse events leading to withdrawal, and events leading to infusion interruption were low.
Clinical Implications
The DELIVER extension data provides important evidence for the sustained benefit of CGRP-targeted therapy in treatment-resistant migraine. Unlike traditional therapies such as anti-inflammatories, antiseizure drugs, and ergots, CGRP-targeted therapies were specifically developed for migraine control. Eptinezumab's intravenous administration achieves peak plasma concentrations within 60 minutes, and its 28-day half-life permits dosing on an every-3-month schedule.
Dr. Ashina noted that the reduction in MMDs "was consistent across demographic subgroups, migraine classifications, history of medication overuse, and number of prior preventative treatment failures." This consistency suggests that eptinezumab targets a fundamental pathway of migraine pain, providing hope for patients who have struggled with traditional preventive therapies.
The study's high completion rate of 90.4% over 18 months indicates excellent real-world tolerability, which may improve persistence and adherence to preventive medication, thereby reducing burden and disability while improving function and reducing work-related impairment.
