At 2 hours after the start of the infusion, headache pain freedom was reported by 23.5% of patients receiving eptinezumab compared to 12% in the placebo group.
Recently published data from the phase 3, parallel-group, double-blind, placebo-controlled RELIEF study (NCT04152083) showed that patients experiencing moderate to severe migraine attacks treated with eptinezumab (Vyepti; Lundbeck) had time to headache and symptom resolution significantly shortened.1,2
The study included 480 patients randomized to 100-mg eptinezumab (n = 238) or placebo (n = 242), administered intravenously within 1 to 6 hours of onset of a qualifying moderate to severe migraine. Lead author Paul K. Winner, DO, director, Palm Beach Headache Center, and colleagues used time to headache pain freedom and time to absence of most bothersome symptom (MBS) as the co-primary end points.
Patients treated with 100-mg eptinezumab achieved the co-primary end points of the time to freedom from headache pain (hazard ratio [HR], 1.54; P <.001) and time to absence of their MBS (HR, 1.75; P <.001) earlier than placebo. The median time after start of infusion to headache freedom was 4 hours for eptinezumab-treated patients and 9 hours for placebo patients, while the median time to absence of MBS was 2 and 3 hours, respectively, for the same groups.
"Historically, patients with migraine have had to wait several weeks for the effect of their preventive medications to manifest,” Winner said in a statement.1 “The RELIEF data in JAMA validates that treatment with Vyepti in the midst of a migraine attack may mitigate the duration and most bothersome symptoms associated with the current attack, while still providing the therapeutic benefit of preventing future attacks. Furthermore, an active migraine would not be an obstacle for initiating preventive treatment with Vyepti."
Eptinezumab, a humanized monoclonal antibody that binds to calcitonin gene-related peptide (CGRP) ligand and blocks its binding to the receptor, received FDA approval in February 2020 for the prevention of migraine in adults, with a recommended dose of 100 mg to be administered quarterly.
Winner and colleagues documented an odds ratio (OR) of 2.27 for achieving 2-hour headache pain freedom (95% CI, 1.39-3.72; P <.001) in favor of eptinezumab (23.5%) compared to placebo (12%; difference, 11.6% [95% CI, 4.78-18.31]). Additionally, the OR of achieving 2-hour absence of MBS was 2.25 (95% CI, 1.55-3.25; P <.001) in favor of eptinezumab (55.5%) vs placebo (35.8%; difference, 19.6% [95% CI, 10.87-28.39]).
Patients continued to see statistically significant benefits on both headache pain freedom and MBS at 4 hours as well. The OR of rescue medication use within 24 hours was 0.31 (95% CI, 0.21-0.45; P <.001) favoring eptinezumab (31.5%) vs placebo (59.9%; difference, –28.4% [95% CI, –36.95 to –19.86]).
Consistent with previous clinical trials, eptinezumab demonstrated a safe and well-tolerated profile, with hypersensitivity (such as allergic reaction; 5 of 238 [2.1%]) being the most frequently reported treatment-emergent adverse event (TEAE). Three of the events occurred during the infusion and the remaining 2 occurred after the infusion was complete. No serious TEAEs were reported in either treatment group.
"We purposelydesigned the RELIEF study with the knowledge that patients experiencing high-frequency of migraine attacks could have an active migraine when administered preventive treatment with Vyepti,” Roger Cady, MD, vice president, Neurology, Lundbeck, said in a statement. “In the RELIEF study, administering VYEPTI during an active migraine resolved headache and migraine-associated symptoms, and extended the time to the next migraine attack vs. placebo. These data provide important insights into the spectrum of therapeutic needs of patients experiencing frequent migraine episodes.”
A recently conducted analysis of the PROMISE-2 trial (NCT02974153) of eptinezumab showed a patient response to treatment within the first month and was predictive of sustained response to treatment throughout all 6 months of the study.3 PROMISE-2, along with PROMISE-1 (NCT02559895), were the 2 pivotal studies that supported the FDA decision to approve the drug.