BACKGROUND: PROMISE-2 was a phase 3, randomized, double-blind, placebo-controlled study that evaluated the efficacy and safety of repeat intravenous (IV) doses of the calcitonin gene-related peptide-targeted monoclonal antibody eptinezumab (ALD403) for migraine prevention in adults with chronic migraine. This report describes the results of PROMISE-2 through 24weeks of treatment.METHODS: Patients received up to two 30-min IV administrations of eptinezumab 100mg, 300mg, or placebo separated by 12weeks. Patients recorded migraine and headache endpoints in a daily eDiary. Additional assessments, including patient-reported outcomes, were performed at regularly scheduled clinic visits throughout the 32-week study period (screening, day 0, and weeks 2, 4, 8, 12, 16, 20, 24, and 32).RESULTS: A total of 1072 adults received treatment: eptinezumab 100mg, n=356; eptinezumab 300mg, n=350; placebo, n=366. The reduction in mean monthly migraine days observed during the first dosing interval (100mg, -7.7days; 300mg, -8.2days; placebo, -5.6days) was further decreased after an additional dose (100mg, -8.2days; 300mg, -8.8days; placebo, -6.2days), with both doses of eptinezumab demonstrating consistently greater reductions from baseline compared to placebo. The ≥50% and≥75% migraine responder rates (MRRs) increased after a second dose, with more eptinezumab-treated patients experiencing migraine response than placebo patients (≥50% MRRs weeks 13-24: 100mg, 61.0%; 300mg, 64.0%; placebo, 44.0%; and≥75% MRRs weeks 13-24: 100mg, 39.3%; 300mg, 43.1%; placebo, 23.8%). The percentages of patients who improved on patient-reported outcomes, including the Headache Impact Test and Patient Global Impression of Change, increased following the second dose administration at week 12, and were greater with eptinezumab than with placebo at all time points. No new safety concerns were identified with the second dose regarding the incidence, nature, and severity of treatment-emergent adverse events.CONCLUSION: Eptinezumab 100mg or 300mg administered IV at day 0 and repeated at week 12 provided sustained migraine preventive benefit over a full 24weeks and demonstrated an acceptable safety profile in patients with chronic migraine.TRIAL REGISTRATION: ClinicalTrials.gov (Identifier: NCT02974153 ). Registered November 23, 2016.
View details for DOI 10.1186/s10194-020-01186-3
View details for PubMedID 33023473