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Abstract Details

Differences in Exposure Between Intravenously (IV) Administered Eptinezumab and Subcutaneously (SC) Administered CGRP Inhibitor Monoclonal Antibodies After Single Therapeutic Doses
Headache
P14 - Poster Session 14 (8:00 AM-9:00 AM)
7-002

To compare the relative dose-normalized exposures of IV-administered eptinezumab vs SC-administered fremanezumab, galcanezumab, and erenumab.
Three SC-administered CGRP (calcitonin gene-related peptide) inhibitor monoclonal antibodies (mAbs) have been approved for the prevention of migraine, and one IV-administered mAb is currently under regulatory review. Differences in exposure profiles following administration of these agents may provide a rationale for different dose levels and dosing schedules (ie, every 4 weeks vs every 12 weeks). 

Population pharmacokinetic analysis of eptinezumab was performed using a non-linear mixed-effects approach as recommended by FDA guidance. Data for comparator agents was obtained from published literature and regulatory sources. The analysis included studies assessing single IV doses of eptinezumab (100mg, 300mg) and single SC doses of fremanezumab (225mg, 675mg), galcanezumab (75mg, 200mg), and erenumab (70mg, 140mg). Dose-normalized maximum plasma concentrations (Cmax) and area under the drug concentration-time curve from zero to infinity (AUC0-∞) were calculated for each agent.

Dose-normalized Cmax values for eptinezumab, fremanezumab, galcanezumab, and erenumab (after a single treatment at a therapeutic dose, as specified) were 0.37-0.38, 0.13-0.16, 0.07-0.09, and 0.09-0.11mg/mL/mg, respectively. This represents a greater exposure in dose-normalized Cmax for eptinezumab when compared with fremanezumab (³140%), galcanezumab (³337%), and erenumab (³328%). The corresponding values for AUC0-∞ were 264-270, 189-197, 40-45, and 57-60 hr·mg/mL/mg, which represents a greater exposure for eptinezumab by dose-normalized AUC0-∞ when compared to fremanezumab (³34%), galcanezumab (³487%), and erenumab (³342%). 
The results indicate that, per mg of drug administered, eptinezumab is associated with 2.4?4.1-fold greater exposure than fremanezumab, galcanezumab, and erenumab (as assessed by Cmax) and 1.4-6.8-fold greater exposure (as assessed by AUC0-∞) when all agents were administered at single therapeutic doses. These data support a lower dose level and a prolonged administration schedule for eptinezumab when compared with these agents.
Authors/Disclosures

PRESENTER 		No disclosure on file
No disclosure on file
No disclosure on file
Barbara Schaeffler No disclosure on file