Efficacy and safety of eptinezumab in patients with chronic migraine

Abstract

ObjectiveTo evaluate the efficacy and safety of eptinezumab, a humanized anti–calcitonin gene-related peptide monoclonal antibody, in the preventive treatment of chronic migraine (CM).MethodsThe Prevention of Migraine via Intravenous ALD403 Safety and Efficacy–2 (PROMISE-2) study was a phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Adults with CM were randomly assigned to receive IV eptinezumab 100 mg, eptinezumab 300 mg, or placebo administered on day 0 and week 12. The primary endpoint was change from baseline in mean monthly migraine days (MMDs) over weeks 1 to 12.ResultsAmong treated participants (n = 1,072), baseline mean number of MMDs was ≈16.1 across groups. Treatment with eptinezumab 100 and 300 mg was associated with significant reductions in MMDs across weeks 1 to 12 compared with placebo (placebo −5.6, 100 mg −7.7, p < 0.0001 vs placebo; 300 mg −8.2, p < 0.0001 vs placebo). Treatment-emergent adverse events (TEAEs) were reported by 43.5% (100 mg), 52.0% (300 mg), and 46.7% (placebo) of patients. Nasopharyngitis was the only TEAE reported for >2% of eptinezumab-treated patients at an incidence of >2% over placebo; it occurred in the 300 mg eptinezumab arm (eptinezumab 9.4%, placebo 6.0%).ConclusionIn patients with CM, eptinezumab 100 and 300 mg was associated with a significant reduction in MMDs from the day after IV administration through week 12, was well tolerated, and demonstrated an acceptable safety profile.Classification of evidenceThis study provides Class I evidence that for patients with CM, a single dose of eptinezumab reduces MMDs over 12 weeks of treatment.ClinicalTrials.gov identifierNCT02974153.

Population pharmacokinetic and exposure‐response analysis of eptinezumab in the treatment of episodic and chronic migraine

“…Renal function was normal in 55.3% of patients/subjects, with mild or moderate decreases in estimated glomerular filtration rate (eGFR) in 41.9% and 2.7% of patients/subjects, respectively. The average MMD during the screening period of studies CLIN‐005, CLIN‐006, and CLIN‐011 was approximately 14 days (CLIN‐005, 16.5 MMD; CLIN‐006, 8.7 MMD; CLIN‐011, 16.1 MMD).…”

“…As anticipated for the IV route of administration, eptinezumab had a short T max of 30 to 60 minutes, which corresponded with the end of the IV delivery. This rapid achievement of C max may provide a pharmacokinetic explanation for the rapid onset of effect observed in clinical trials . The short T max values for eptinezumab are in contrast to the longer median values for single doses of erenumab (4‐11 days), fremanezumab (5‐11 days), and galcanezumab (7‐14 days), which are administered subcutaneously.…”

“…PK parameters from the final population PK model were used to derive exposure metrics: area under the curve from time 0 to 12 weeks (AUC 0‐12wk ), maximum concentration ( C max ), average concentration ( C avg ), and trough concentration ( C trough ). The exposure‐response relationship of plasma eptinezumab was evaluated using these single‐dose exposure parameters and the change in frequency of MMD (weeks 1‐12) from studies CLIN‐005, CLIN‐006, and CLIN‐011 . A saturable inhibitory maximum‐effect ( E max ) model was used to assess relationships between the exposure metrics of eptinezumab and the reduction in MMD.…”

“…Eptinezumab (ALD403) is a humanized anti‐CGRP antibody with an IgG1 backbone that binds to both the α and β forms of CGRP and is currently under development for migraine prevention. In controlled clinical studies, it has demonstrated efficacy compared to placebo in the prevention of migraine in patients with episodic migraine (EM) and chronic migraine (CM) . This report describes a population PK modeling analysis conducted for the IV administration of eptinezumab at single doses of 10‐1000 mg in healthy subjects and in patients with EM and CM from eight studies in the eptinezumab clinical program .…”

“…In controlled clinical studies, it has demonstrated efficacy compared to placebo in the prevention of migraine in patients with episodic migraine (EM) and chronic migraine (CM) . This report describes a population PK modeling analysis conducted for the IV administration of eptinezumab at single doses of 10‐1000 mg in healthy subjects and in patients with EM and CM from eight studies in the eptinezumab clinical program . A further goal was to assess the dose‐ and exposure‐response relationships of selected endpoints in patients with EM and CM who received eptinezumab.…”