Skip to main content

Advertisement

SpringerLink
Log in

TEV-48125: a Review of a Monoclonal CGRP Antibody in Development for the Preventive Treatment of Migraine

  • Antibodies and Other Biological Treatments (M Bigal, Section Editor)
  • Published:
Current Pain and Headache Reports Aims and scope Submit manuscript

Abstract

Calcitonin gene-related peptide (CGRP) is a 37-amino-acid neuropeptide whose involvement in migraine pathophysiology is well established. Originally migraine was believed to be a disease of the vasculature, but research has highlighted this to be a disease of the brain with CGRP playing an important role. While targeting CGRP using small molecule antagonists against the receptor has been effective, long-term use of these agents has not been possible due to safety concerns and/or formulation challenges. Recent advances in therapeutic antibodies have opened up new possibilities for treatment of migraine. TEV-48125 is one of four monoclonal antibodies targeting CGRP or its receptors, currently in development for the preventive treatment of migraine. This article discusses the in vitro and in vivo pharmacology of TEV-48125 as well as highlighting its safety profile through the six Phase 1 studies that have been conducted. Finally, the current state of development and future studies for TEV-48125 will be reviewed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Ho TW, Edvinsson L, Goadsby PJ. CGRP and its receptors provide new insights into migraine pathophysiology. Nat Rev Neurol. 2010;6:573–82. Pivotal paper discussing the implications of CGRP science on our understanding of the pathophysiology of migraine.

    Article  CAS  PubMed  Google Scholar 

  2. Goadsby PJ. Calcitonin gene-related peptide (CGRP) antagonists and migraine: is this a new era? Neurology. 2008;70:1300–1.

    Article  PubMed  Google Scholar 

  3. Silberstein SD, Edvinsson L. Is CGRP a marker for chronic migraine? Neurology. 2013;81:1184–5. Editorial suggesting that CGRP is a marker of headache frequency, since its levels are higher in chronic than in episodic migraine.

    Article  PubMed  Google Scholar 

  4. Bigal ME, Walter S, Rapoport AM. Calcitonin gene-related peptide (CGRP) and migraine current understanding and state of development. Headache. 2013;53:1230–44. Paper focusing on the role of CGRP in migraine and potential implication of its chronic inhibition.

    Article  PubMed  Google Scholar 

  5. Schutz B, Mauer D, Salmon AM, Changeux JP, Zimmer A. Analysis of the cellular expression pattern of beta-CGRP in alpha-CGRP-deficient mice. J Comp Neurol. 2004;476:32–43.

    Article  PubMed  Google Scholar 

  6. Lennerz JK, Ruhle V, Ceppa EP, Neuhuber WL, Bunnett NW, Grady EF, et al. Calcitonin receptor-like receptor (CLR), receptor activity-modifying protein 1 (RAMP1), and calcitonin gene-related peptide (CGRP) immunoreactivity in the rat trigeminovascular system: differences between peripheral and central CGRP receptor distribution. J Comp Neurol. 2008;507:1277–99.

    Article  CAS  PubMed  Google Scholar 

  7. Thalakoti S, Patil VV, Damodaram S, Vause CV, Langford LE, Freeman SE, et al. Neuron-glia signaling in trigeminal ganglion: implications for migraine pathology. Headache. 2007;47:1008–23. discussion 1024–1005.

    Article  PubMed Central  PubMed  Google Scholar 

  8. van Rossum D, Hanisch UK, Quirion R. Neuroanatomical localization, pharmacological characterization and functions of CGRP, related peptides and their receptors. Neurosci Biobehav Rev. 1997;21:649–78.

    Article  PubMed  Google Scholar 

  9. Eftekhari S, Edvinsson L. Possible sites of action of the new calcitonin gene-related peptide receptor antagonists. Ther Adv Neurol Disord. 2010;3:369–78.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Raddant AC, Russo AF. Calcitonin gene-related peptide in migraine: intersection of peripheral inflammation and central modulation. Expert Rev Mol Med. 2011;13:e36.

    Article  PubMed Central  PubMed  Google Scholar 

  11. Ho TW, Ferrari MD, Dodick DW, Galet V, Kost J, Fan X, et al. Efficacy and tolerability of MK-0974 (telcagepant), a new oral antagonist of calcitonin gene-related peptide receptor, compared with zolmitriptan for acute migraine: a randomised, placebo-controlled, parallel-treatment trial. Lancet. 2008;372:2115–23.

    Article  CAS  PubMed  Google Scholar 

  12. Hewitt DJ, Aurora SK, Dodick DW, Goadsby PJ, Ge YJ, Bachman R, et al. Randomized controlled trial of the CGRP receptor antagonist MK-3207 in the acute treatment of migraine. Cephalalgia Int J Headache. 2011;31:712–22.

    Article  Google Scholar 

  13. Ho TW, Connor KM, Zhang Y, Pearlman E, Koppenhaver J, Fan X, et al. Randomized controlled trial of the CGRP receptor antagonist telcagepant for migraine prevention. Neurology. 2014;83:958–66.

    Article  CAS  PubMed  Google Scholar 

  14. Silberstein SD. Emerging target-based paradigms to prevent and treat migraine. Clin Pharmacol Ther. 2013;93:78–85.

    Article  CAS  PubMed  Google Scholar 

  15. Hoffmann J, Goadsby PJ. New agents for acute treatment of migraine: CGRP receptor antagonists, iNOS inhibitors. Curr Treat Options Neurol. 2012;14:50–9.

    Article  PubMed  Google Scholar 

  16. Bigal ME, Escandon R, Bronson M, Walter S, Sudworth M, Huggins JP, et al. Safety and tolerability of LBR-101, a humanized monoclonal antibody that blocks the binding of CGRP to its receptor: results of the Phase 1 program. Cephalalgia Int J Headache. 2013. Paper summarizing the tolerability of TEV-48315 across phase 1.

  17. Walter S, Alibhoy A, Escandon R, Bigal ME. Evaluation of cardiovascular parameters in cynomolgus monkeys following IV administration of LBR-101, a monoclonal antibody against calcitonin gene-related peptide. mAbs. 2014;6:871–8. Paper describing the effects of short and long term potent inhibition of CGRP on cardiovascular parameters in monkeys.

    Article  PubMed  Google Scholar 

  18. Chan KY, Edvinsson L, Eftekhari S, Kimblad PO, Kane SA, Lynch J, et al. Characterization of the calcitonin gene-related peptide receptor antagonist telcagepant (MK-0974) in human isolated coronary arteries. J Pharmacol Exp Ther. 2010;334:746–52.

    Article  CAS  PubMed  Google Scholar 

  19. Lynch JJ, Shen YT, Pittman TJ, Anderson KD, Koblan KS, Gould RJ, et al. Effects of the prototype serotonin 5-HT(1B/1D) receptor agonist sumatriptan and the calcitonin gene-related peptide (CGRP) receptor antagonist CGRP(8-37) on myocardial reactive hyperemic response in conscious dogs. Eur J Pharmacol. 2009;623:96–102.

    Article  CAS  PubMed  Google Scholar 

  20. Chaitman BR, Ho AP, Behm MO, Rowe JF, Palcza JS, Laethem T, et al. A randomized, placebo-controlled study of the effects of telcagepant on exercise time in patients with stable angina. Clin Pharmacol Ther. 2012;91:459–66.

    Article  CAS  PubMed  Google Scholar 

  21. Van der Schueren BJ, Blanchard R, Murphy MG, Palcza J, De Lepeleire I, Van Hecken A, et al. The potent calcitonin gene-related peptide receptor antagonist, telcagepant, does not affect nitroglycerin-induced vasodilation in healthy men. Br J Clin Pharmacol. 2011;71:708–17.

    Article  PubMed Central  PubMed  Google Scholar 

  22. Bigal ME, Walter S, Rapoport AM. The vasodilatory activity of CGRP: a response. Headache. 2014;54:748–9.

    Article  PubMed  Google Scholar 

  23. Bigal ME, Walter S, Bronson M, Alibhoy A, Escandon R. Cardiovascular and hemodynamic parameters in women following prolonged CGRP inhibition using LBR-101, a monoclonal antibody against CGRP. Cephalalgia Int J Headache. 2014.

Download references

Compliance with Ethics Guidelines

Conflict of Interest

At the time of this writting, Sarah Walter was a full-time employee of Teva, the company developing TEV-48125. Before that, Dr. Walter was a full-time employee of Labrys Biologics Inc., which was acquired by Teva and was responsible for the development of TEV-48125 (LBR-101) until the acquisition.

Marcelo E. Bigal reports being a full-time employee from Teva during the conduct of the study, and Dr. Bigal is a full-time employee of Teva, the maker of TEV-48125. Before that, Dr. Bigal was the Chief Medical Officer of Labrys Biologics Inc.

Human and Animal Rights and Informed Consent

All animal and human studies reported in this paper are part of the regulatory submission for TEV-48125 and were reviewed and approved by animal and human investigational review boards (IRB). IRB approved consent forms were obtained by all subjects participating in the studies mentioned in this review paper.

Author information

Authors and Affiliations

  1. Migraine & Headache, Clinical Development, Global Branded R&D, Teva Pharmaceuticals, 41 Moores Road, Frazer, PA, 19355, USA

    Sarah Walter & Marcelo E. Bigal

Authors
  1. Sarah Walter
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marcelo E. Bigal
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marcelo E. Bigal.

Additional information

This article is part of the Topical Collection on Antibodies and Other Biological Treatments

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Walter, S., Bigal, M.E. TEV-48125: a Review of a Monoclonal CGRP Antibody in Development for the Preventive Treatment of Migraine. Curr Pain Headache Rep 19, 6 (2015). https://doi.org/10.1007/s11916-015-0476-1

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11916-015-0476-1

Keywords

Search

Navigation