Safety and efficacy of LY2951742, a monoclonal antibody to calcitonin gene-related peptide, for the prevention of migraine: A phase 2, randomised, double-blind, placebo-controlled study

The Lancet Neurology

Volumn 13, Issue 9, 2014, Pages 885-892

  Dodick, David W ^a   Goadsby, Peter J ^b,c   Spierings, Egilius L H ^d,e,f   Scherer, Joel C ^g   Sweeney, Steven P ^h   Grayzel, David S ^h  

^a MAYO CLINIC   (United States)

^b KING'S COLLEGE LONDON   (United Kingdom)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d MASSACHUSETTS GENERAL HOSPITAL   (United States)

^e TUFTS UNIVERSITY SCHOOL OF DENTAL MEDICINE   (United States)

^f TUFTS MEDICAL CENTER   (United States)

^g ELI LILLY AND COMPANY   (United States)

^h Arteaus Therapeutics   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CALCITONIN GENE RELATED PEPTIDE; LY 2951742; MONOCLONAL ANTIBODY; PLACEBO; UNCLASSIFIED DRUG;

ABDOMINAL PAIN; ADULT; AGED; ARTHRALGIA; ARTICLE; BACKACHE; CONTROLLED STUDY; DIZZINESS; DRUG SAFETY; DRUG WITHDRAWAL; FEMALE; HUMAN; HYPERTENSION; INJECTION SITE ERYTHEMA; INJECTION SITE PAIN; INTENTION TO TREAT ANALYSIS; LIMB PAIN; MAJOR CLINICAL STUDY; MALE; MIGRAINE; NAUSEA; NECK PAIN; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIAL; RASH; RHINOPHARYNGITIS; SINUSITIS; TOOTH PAIN; UNITED STATES; UPPER RESPIRATORY TRACT INFECTION; VIRAL GASTROENTERITIS; ADOLESCENT; ANTAGONISTS AND INHIBITORS; CLINICAL TRIAL; DOUBLE BLIND PROCEDURE; IMMUNOLOGY; MIDDLE AGED; MIGRAINE DISORDERS; MULTICENTER STUDY; SUBCUTANEOUS DRUG ADMINISTRATION; TIME; TREATMENT OUTCOME; YOUNG ADULT;

ADOLESCENT; ADULT; AGED; ANTIBODIES, MONOCLONAL, HUMANIZED; CALCITONIN GENE-RELATED PEPTIDE; DOUBLE-BLIND METHOD; FEMALE; HUMANS; INJECTIONS, SUBCUTANEOUS; MALE; MIDDLE AGED; MIGRAINE DISORDERS; PLACEBOS; TIME FACTORS; TREATMENT OUTCOME; YOUNG ADULT;

EID: 84906262129     PISSN: 14744422     EISSN: 14744465     Source Type: Journal    
DOI: 10.1016/S1474-4422(14)70128-0     Document Type: Article

References (44)

1. Murray CJ, Vos T, Lozano R, et al. Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012, 380:2197-2223.
2. Munakata J, Hazard E, Serrano D, et al. Economic burden of transformed migraine: results from the American Migraine Prevalence and Prevention (AMPP) Study. Headache 2009, 49:498-508.
3. Natoli JL, Manack A, Dean B, et al. Global prevalence of chronic migraine: a systematic review. Cephalalgia 2010, 30:599-609.
4. Bigal ME, Lipton RB Concepts and mechanisms of migraine chronification. Headache 2008, 48:7-15.
5. Lipton RB Chronic migraine, classification, differential diagnosis, and epidemiology. Headache 2011, 51(suppl 2):77-83.
6. Bigal ME, Lipton RB Modifiable risk factors for migraine progression. Headache 2006, 46:1334-1343.
7. Diener HC, Dodick DW, Goadsby PJ, Lipton RB, Olesen J, Silberstein SD Chronic migraine-classification, characteristics and treatment. Nat Rev Neurol 2011, 8:162-171.
8. Goadsby PJ Therapeutic prospects for migraine: can paradise be regained?. Ann Neurol 2014, 74:423-434.
9. Eftekhari S, Edvinsson L Calcitonin gene-related peptide (CGRP) and its receptor components in human and rat spinal trigeminal nucleus and spinal cord at C1-level. BMC Neurosci 2011, 12:112.
10. Lennerz JK, Ruhle V, Ceppa EP, 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, 507:1277-1299.
11. Warfvinge K, Edvinsson L Pearls and pitfalls in neural CGRP immunohistochemistry. Cephalalgia 2013, 33:593-603.
12. Goadsby PJ, Edvinsson L, Ekman R Release of vasoactive peptides in the extracerebral circulation of humans and the cat during activation of the trigeminovascular system. Ann Neurol 1988, 23:193-196.
13. Lassen LH, Haderslev PA, Jacobsen VB, Iversen HK, Sperling B, Olesen J CGRP may play a causative role in migraine. Cephalalgia 2002, 22:54-61.
14. Juhasz G, Zsombok T, Jakab B, Nemeth J, Szolcsanyi J, Bagdy G Sumatriptan causes parallel decrease in plasma calcitonin gene-related peptide (CGRP) concentration and migraine headache during nitroglycerin induced migraine attack. Cephalalgia 2005, 25:179-183.
15. Hewitt DJ, Aurora SK, Dodick DW, et al. Randomized controlled trial of the CGRP receptor antagonist MK-3207 in the acute treatment of migraine. Cephalalgia 2011, 31:712-722.
16. Ho TW, Ferrari MD, Dodick DW, 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, 372:2115-2123.
17. Olesen J, Diener HC, Husstedt IW, et al. Calcitonin gene-related peptide receptor antagonist BIBN 4096 BS for the acute treatment of migraine. N Engl J Med 2004, 350:1104-1110.
18. Marcus R, Goadsby PJ, Dodick D, Stock D, Manos G, Fischer TZ BMS-927711 for the acute treatment of migraine: a double-blind, randomized, placebo controlled, dose-ranging trial. Cephalalgia 2014, 34:114-125.
19. Mould DR, Sweeney KR The pharmacokinetics and pharmacodynamics of monoclonal antibodies-mechanistic modeling applied to drug development. Curr Opin Drug Discov Devel 2007, 10:84-96.
20. Wu H, Dall'Acqua WF Humanized antibodies and their applications. Methods 2005, 36:1-2.
21. Olesen J International Classification of Headache Disorders, Second Edition (ICHD-2): current status and future revisions. Cephalalgia 2006, 26:1409-1410.
22. de Hoon J, Montieth D, Vermeersch S, et al. Safety, pharmacokinetics, and pharmacodynamics of LY2951742: a monoclonal antibody targeting CGRP. Cephalalgia 2013, 33(suppl 8):247. (abstr).
23. Vermeersch S, Van Hecken A, Abu-Raddad E, et al. Translational pharmacodynamics of CGRP monoclonal antibody LY2951742 in capsaicin-induced dermal blood flow model. Cephalalgia 2013, 33(suppl 8):249-250. (abstr).
24. Brandes JL, Saper JR, Diamond M, et al. Topiramate for migraine prevention: a randomized controlled trial. JAMA 2004, 291:965-973.
25. Silberstein SD, Neto W, Schmitt J, Jacobs D Topiramate in migraine prevention: results of a large controlled trial. Arch Neurol 2004, 61:490-495.
26. Freitag FG, Collins SD, Carlson HA, et al. A randomized trial of divalproex sodium extended-release tablets in migraine prophylaxis. Neurology 2002, 58:1652-1659.
27. Dworkin RH, Turk DC, McDermott MP, et al. Interpreting the clinical importance of group differences in chronic pain clinical trials: IMMPACT recommendations. Pain 2009, 146:238-244.
28. Silberstein SD, Holland S, Freitag F, Dodick DW, Argoff C, Ashman E Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology 2012, 78:1337-1345.
29. Pringsheim T, Davenport W, Mackie G, et al. Canadian Headache Society guideline for migraine prophylaxis. Can J Neurol Sci 2012, 39(suppl 2):S1-59.
30. de Groot FM, Voogt-Bode A, Passchier J, Berger MY, Koes BW, Verhagen AP Headache: the placebo effects in the control groups in randomized clinical trials; an analysis of systematic reviews. J Manipulative Physiol Ther 2011, 34:297-305.
31. Diener HC, Schorn CF, Bingel U, Dodick DW The importance of placebo in headache research. Cephalalgia 2008, 28:1003-1011.
32. Ho TW, Edvinsson L, Goadsby PJ CGRP and its receptors provide new insights into migraine pathophysiology. Nat Rev Neurol 2010, 6:573-582.
33. Tfelt-Hansen P, Olesen J Possible site of action of CGRP antagonists in migraine. Cephalalgia 2011, 31:748-750.
34. Gupta VK CSD, BBB and MMP-9 elevations: animal experiments versus clinical phenomena in migraine. Expert Rev Neurother 2009, 9:1595-1614.
35. Gursoy-Ozdemir Y, Qiu J, Matsuoka N, et al. Cortical spreading depression activates and upregulates MMP-9. J Clin Invest 2004, 113:1447-1455.
36. Lafata JE, Tunceli O, Cerghet M, Sharma KP, Lipton RB The use of migraine preventive medications among patients with and without migraine headaches. Cephalalgia 2010, 30:97-104.
37. Evans RW, Linde M Expert opinion: adherence to prophylactic migraine medication. Headache 2009, 49:1054-1058.
38. Bigal ME, Lipton RB Modifiable risk factors for migraine progression (or for chronic daily headaches)-clinical lessons. Headache 2006, 46(suppl 3suppl 3):S144-S146.
39. Stokes M, Becker WJ, Lipton RB, et al. Cost of health care among patients with chronic and episodic migraine in Canada and the USA: results from the International Burden of Migraine Study (IBMS). Headache 2011, 51:1058-1077.
40. Payne KA, Varon SF, Kawata AK, et al. The International Burden of Migraine Study (IBMS): study design, methodology, and baseline cohort characteristics. Cephalalgia 2011, 31:1116-1130.
41. Blumenfeld AM, Varon SF, Wilcox TK, et al. Disability, HRQoL and resource use among chronic and episodic migraineurs: results from the International Burden of Migraine Study (IBMS). Cephalalgia 2011, 31:301-315.
42. Cernuda-Morollon E, Larrosa D, Ramon C, Vega J, Martinez-Camblor P, Pascual J Interictal increase of CGRP levels in peripheral blood as a biomarker for chronic migraine. Neurology 2013, 81:1191-1196.
43. Bigal ME, Escandon R, Bronson M, 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 2013, 34:483-492.
44. Bulpitt CJ Confidence intervals. Lancet 1987, 1:494-497.