Erratum

Corrigendum to: Abstracts from the International Headache Congress 2023

Late breaking Author Index (DOI: 10.1177/03331024231202615).

An abstract missing from the Late Breaking Abstracts document has been appended to this corrigendum (IHC23-INDLB-001), below. The Late Breaking Author Index entries have been updated accordingly to direct readers to this location.

Missing abstract

Headache pathophysiology - Basic science

IHC23-INDLB-001

CNS target engagement by the anti-CGRP mAb fremanezumab in the cerebrospinal fluid of healthy volunteers

Jacki Rorabaugh¹, Juline M Bryson¹, Edward Hellriegel¹, Giulia Ghibellini¹, Hang Zeng¹, Xiaofeng Lu¹, Thelma Angeles¹, Olga Szilagyi², James Wang¹, Steve Mallet¹, Steve Barash¹, Laura Rabinovich-Guilatt³, Peter J Goadsby^4,5, Andrew H Ahn¹

¹Teva Pharmaceutical Industries Ltd, West Chester PA, USA. ²Teva Pharmaceutical Industries Ltd, Debrecen, Hungary. ³Teva Pharmaceutical Industries Ltd, Netanya, Israel. ⁴2. NIHR King's Clinical Research Facility & SLaM Biomedical Research Centre, and Wolfson CARD, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom. ⁵3. Department of Neurology, University of California, Los Angeles CA, USA

Abstract

Objective: Calcitonin gene-related peptide (CGRP) targeted monoclonal antibodies are effective in the prevention of migraine, although whether the site of action is restricted to the periphery or also includes the central nervous system remains unresolved. Our objective was to examine if fremanezumab could be detected in humans in the cerebrospinal fluid (CSF) and demonstrate target engagement: binding and stabilization of CGRP.

Methods: In this open label phase 1 study in healthy volunteers we infused a single dose of fremanezumab (n = 19; 900 mg; i.v.) and collected a single CSF sample and a series of blood samples from each participant at predetermined times post-infusion: 24 hr (n = 5), 72 hr (n = 5), 15 days (n = 5) and at 30 days (n = 4). A separate group of untreated participants, providing CSF and blood, served as controls (n = 5). Fremanezumab and total CGRP were analyzed in all samples. Lower limit of quantification (LLOQ) for fremanezumab = 250 ng/mL plasma; 30 ng/mL CSF and total CGRP = 2.0 pg/mL plasma; 0.25 pg/mL CSF.

Results: The safety and exposure profile of fremanezumab in plasma was consistent with previous studies. In the CSF, fremanezumab concentration ranged from 134 to 244 ng/mL plateauing by 72 hr, with notably sustained concentrations through day 30. The overall partition of fremanezumab in CSF from plasma ranged from 0.06% to 0.36%. Using a highly sensitive and specific assay for total CGRP we detected a rise in CGRP after fremanezumab infusion. In plasma, total CGRP increased, with a range from 57.6 to 359 pg/mL. In the CSF, total CGRP was quantifiable at 24 hr after infusion and sustained through 30 days, with a range from 1.79 to 3.35 pg/mL.

Conclusion: This study affirms the potential for fremanezumab to access the CNS and engage its target. Further work is needed to better understand its clinical significance.