Translational pharmacodynamics of calcitonin gene-related peptide monoclonal antibody LY2951742 in a capsaicin-induced dermal blood flow model

Journal of Pharmacology and Experimental Therapeutics

Volumn 354, Issue 3, 2015, Pages 350-357

  Vermeersch, Steve ^a   Benschop, Robert J ^b   Van Hecken, Anne ^a   Monteith, David ^b   Wroblewski, Victor J ^b   Grayzel, David ^c   De Hoon, Jan ^a   Collins, Emily C ^b  

^a UNIVERSITY HOSPITALS LEUVEN   (Belgium)

^b ELI LILLY AND COMPANY   (United States)

^c 400 Technology Square   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIMIGRAINE AGENT; CALCITONIN GENE RELATED PEPTIDE; LSN 2915644; LY 2951742; PLACEBO; UNCLASSIFIED DRUG; BIOLOGICAL MARKER; CAPSAICIN; MONOCLONAL ANTIBODY;

ADULT; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG EXPOSURE; DRUG HALF LIFE; DRUG POTENCY; DRUG SAFETY; EC50; HUMAN; HUMAN EXPERIMENT; MALE; MAXIMUM DRUG EFFECT; MOUSE; NONHUMAN; NORMAL HUMAN; PRIORITY JOURNAL; SINGLE DRUG DOSE; SKIN BLOOD FLOW; TIME TO MAXIMUM PLASMA CONCENTRATION; ADOLESCENT; ANIMAL; BLOOD FLOW; DRUG EFFECTS; INTRADERMAL DRUG ADMINISTRATION; LASER DOPPLER FLOWMETRY; MACACA FASCICULARIS; METABOLISM; MIDDLE AGED; PAIN; PROCEDURES; YOUNG ADULT;

ADMINISTRATION, CUTANEOUS; ADOLESCENT; ADULT; ANIMALS; ANTIBODIES, MONOCLONAL; BIOLOGICAL MARKERS; CALCITONIN GENE-RELATED PEPTIDE; CAPSAICIN; DOUBLE-BLIND METHOD; HUMANS; LASER-DOPPLER FLOWMETRY; MACACA FASCICULARIS; MALE; MIDDLE AGED; PAIN; REGIONAL BLOOD FLOW; YOUNG ADULT;

EID: 84941584598     PISSN: 00223565     EISSN: 15210103     Source Type: Journal    
DOI: 10.1124/jpet.115.224212     Document Type: Article

References (28)

1. Benschop RJ, Collins EC, Darling RJ, Allan BW, Leung D, Conner EM, Nelson J, Gaynor B, Xu J, Wang XF, et al. (2014) Development of a novel antibody to calcitonin gene-related peptide for the treatment of osteoarthritis-related pain. Osteoarthritis Cartilage 22:578-585.
2. Benschop RJ, Gehlert DR, Merchant KM, and Shanafelt AB (2007) inventors, Eli Lilly Co, assignee. Treatment of migraine with anti-cgrp antibodies. Patent WO2007076336 A1. 2007 Jul 5.
3. Bigal ME and Walter S (2014) Monoclonal antibodies for migraine: preventing calcitonin gene-related peptide activity. CNS Drugs 28:389-399.
4. Brain SD, Williams TJ, Tippins JR, Morris HR, and MacIntyre I (1985) Calcitonin gene-related peptide is a potent vasodilator. Nature 313:54-56.
5. Cady RJ, Glenn JR, Smith KM, and Durham PL (2011) Calcitonin gene-related peptide promotes cellular changes in trigeminal neurons and glia implicated in peripheral and central sensitization. Mol Pain 7:94.
6. Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, and Julius D (1997) The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 389:816-824.
7. Dodick DW, Goadsby PJ, Spierings EL, Scherer JC, Sweeney SP, and Grayzel DS (2014) Safety and efficacy of LY2951742, a monoclonal antibody to calcitonin gene-related peptide, for the prevention of migraine: a phase 2, randomised, doubleblind, placebo-controlled study. Lancet Neurol 13:885-892.
8. Eftekhari S, Salvatore CA, Gaspar RC, Roberts R, O'Malley S, Zeng Z, and Edvinsson L (2013) Localization of CGRP receptor components, CGRP, and receptor binding sites in human and rhesus cerebellar cortex. Cerebellum 12:937-949.
9. Gupta P, Harte AL, da Silva NF, Khan H, Barnett AH, Kumar S, Sturdee DW, and McTernan PG (2007) Expression of calcitonin gene-related peptide, adrenomedullin, and receptor modifying proteins in human adipose tissue and alteration in their expression with menopause status. Menopause 14:1031-1038.
10. Hay DL and Poyner DR (2009) Calcitonin gene-related peptide, adrenomedullin and flushing. Maturitas 64:104-108.
11. Hershey JC, Corcoran HA, Baskin EP, Salvatore CA, Mosser S, Williams TM, Koblan KS, Hargreaves RJ, and Kane SA (2005) Investigation of the species selectivity of a nonpeptide CGRP receptor antagonist using a novel pharmacodynamic assay. Regul Pept 127:71-77.
12. Hewitt DJ, Aurora SK, Dodick DW, Goadsby PJ, Ge YJ, Bachman R, Taraborelli D, Fan X, Assaid C, Lines C, et al. (2011) Randomized controlled trial of the CGRP receptor antagonist MK-3207 in the acute treatment of migraine. Cephalalgia 31: 712-722.
13. Hirsch S, Corradini L, Just S, Arndt K, and Doods H (2013) The CGRP receptor antagonist BIBN4096BS peripherally alleviates inflammatory pain in rats. Pain 154:700-707.
14. Ho TW, Ferrari MD, Dodick DW, Galet V, Kost J, Fan X, Leibensperger H, Froman S, Assaid C, Lines C, et al. (2008) 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, paralleltreatment trial. Lancet 372:2115-2123.
15. Li CC, Vermeersch S, Denney WS, Kennedy WP, Palcza J, Gipson A, Han TH, Blanchard R, De Lepeleire I, Depre M, Murphy MG, Van Dyck K, and de Hoon JN (2014) Characterizing the PK/PD relationship for inhibition of capsaicin-induced dermal vasodilatation by MK-3207, an oral CGRP receptor antagonist. Br J Clin Pharmacol 79:831-837.
16. Ma W, Chabot J-G, Schorscher-Petcu A, Hong Y, and Wang Z (2010) CGRP and adrenomedullin as pain-related peptide, in The Calcitonin Gene-Related Peptide Family Form, Function and Future Perspectives (Dickerson IM and Hay DL eds) pp 151-171, Springer Science1Business Media, Dordrecht, The Netherlands.
17. Mapp PI, McWilliams DF, Turley MJ, Hargin E, and Walsh DA (2012) A role for the sensory neuropeptide calcitonin gene-related peptide in endothelial cell proliferation in vivo. Br J Pharmacol 166:1261-1271.
18. Natura G, von Banchet GS, and Schaible HG (2005) Calcitonin gene-related peptide enhances TTX-resistant sodium currents in cultured dorsal root ganglion neurons from adult rats. Pain 116:194-204.
19. Olesen J, Diener HC, Husstedt IW, Goadsby PJ, Hall D, Meier U, Pollentier S, and Lesko LM; BIBN 4096 BS Clinical Proof of Concept Study Group (2004) Calcitonin gene-related peptide receptor antagonist BIBN 4096 BS for the acute treatment of migraine. N Engl J Med 350:1104-1110.
20. Reuter U (2014) Anti-CGRP antibodies: a new approach to migraine prevention. Lancet Neurol 13:857-859.
21. Salvatore CA, Hershey JC, Corcoran HA, Fay JF, Johnston VK, Moore EL, Mosser SD, Burgey CS, Paone DV, Shaw AW, et al. (2008) Pharmacological characterization of MK-0974 [N-[(3R,6S)-6-(2,3-difluorophenyl)-2-oxo-1-(2,2,2-trifluoroethyl)azepan-3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide], a potent and orally active calcitonin gene-related peptide receptor antagonist for the treatment of migraine. J Pharmacol Exp Ther 324:416-421.
22. Salvatore CA, Moore EL, Calamari A, Cook JJ, Michener MS, O'Malley S, Miller PJ, Sur C, Williams DL, Jr, Zeng Z, et al. (2010) Pharmacological properties of MK-3207, a potent and orally active calcitonin gene-related peptide receptor antagonist. J Pharmacol Exp Ther 333:152-160.
23. Segond von Banchet G, Pastor A, Biskup C, Schlegel C, Benndorf K, and Schaible HG (2002) Localization of functional calcitonin gene-related peptide binding sites in a subpopulation of cultured dorsal root ganglion neurons. Neuroscience 110: 131-145.
24. Silberstein SD (2013) Emerging target-based paradigms to prevent and treat migraine. Clin Pharmacol Ther 93:78-85.
25. Sinclair SR, Kane SA, Van der Schueren BJ, Xiao A, Willson KJ, Boyle J, de Lepeleire I, Xu Y, Hickey L, Denney WS, et al. (2010) Inhibition of capsaicin-induced increase in dermal blood flow by the oral CGRP receptor antagonist, telcagepant (MK-0974). Br J Clin Pharmacol 69:15-22.
26. Van der Schueren BJ, de Hoon JN, Vanmolkot FH, Van Hecken A, Depre M, Kane SA, De Lepeleire I, and Sinclair SR (2007) Reproducibility of the capsaicin-induced dermal blood flow response as assessed by laser Doppler perfusion imaging. Br J Clin Pharmacol 64:580-590.
27. Van der Schueren BJ, Rogiers A, Vanmolkot FH, Van Hecken A, Depré M, Kane SA, De Lepeleire I, Sinclair SR, and de Hoon JN (2008) Calcitonin gene-related peptide8-37 antagonizes capsaicin-induced vasodilation in the skin: evaluation of a human in vivo pharmacodynamic model. J Pharmacol Exp Ther 325:248-255.
28. Vermeersch SGG, de Hoon J, De Saint-Hubert B, Derdelinckx I, Serdons K, Bormans G, Reynders T, Declercq R, De Lepeleire I, Kennedy W, et al. (2013) PET imaging in healthy subjects and migraineurs suggests CGRP receptor antagonists do not have to act centrally to achieve clinical efficacy. J Headache Pain 14 (Suppl 1): P224.