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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.
Lancet Neurol. 2014 Sep; 13(9):885-92.LN

Abstract

BACKGROUND

Migraine remains poorly treated, with few effective preventive drugs available. We assessed the safety and efficacy of LY2951742, a fully humanised monoclonal antibody to calcitonin gene-related peptide, for migraine prevention.

METHODS

We did a randomised, double-blind, placebo-controlled, phase 2 proof-of-concept study at 35 centres in the USA. Patients aged 18-65 years with four to 14 migraine headache days per month were randomly assigned (1:1) to LY2951742 or placebo by a computerised randomisation scheme. LY2951742 (150 mg) or placebo were given as a subcutaneous injection once every 2 weeks for 12 weeks. The primary endpoint was the mean change in number of migraine headache days per 28-day period assessed at 9-12 weeks. Safety was assessed over 24 weeks, including the 12-week treatment period and the subsequent 12 weeks after study drug administration. Patients and treating investigators were masked to treatment allocation. Analyses were by intention to treat. A mixed-effects model of repeated measures was used, including patient baseline value, treatment, visit, and treatment-by-visit interaction as fixed effects, and patients as random effects. Safety measures were analysed according to the treatment received. This study has been completed and is registered with ClinicalTrials.gov, NCT01625988.

FINDINGS

Between July 31, 2012, and Sept 18, 2013, 218 patients were randomly assigned to LY2951742 (n=108, but one patient withdrew before treatment) or placebo (n=110). The mean change from baseline to week 12 in the number of migraine headache days was -4·2 (SD 3·1; 62·5% decrease) in the LY2951742 group compared with -3·0 (SD 3·0; 42·3% decrease) in the placebo group (least-squares mean difference -1·2, 90% CI -1·9 to -0·6; p=0·0030). Adverse events that occurred more frequently with LY2951742 than with placebo included injection site pain, erythema, or both (21 [20%] of 107 vs seven [6%] of 110), upper respiratory tract infections (18 [17%] vs ten [9%]), and abdominal pain (six [6%] vs three [3%]). There were two serious adverse events reported in the treatment arm and four in the placebo arm, none of which were deemed to be related to the study drug.

INTERPRETATION

These results provide preliminary evidence that LY2951742 might be beneficial in migraine prevention and provide support for the role of calcitonin gene-related peptide in the pathogenesis of migraine. Further controlled studies are needed to assess the safety and efficacy of monoclonal calcitonin gene-related peptide antibodies for the preventive treatment of migraine.

FUNDING

Arteaus Therapeutics.

Authors+Show Affiliations

Department of Neurology, Mayo Clinic, Phoenix, AZ, USA. Electronic address: dodick.david@mayo.edu.NIHR Wellcome Trust Clinical Research Facility, Kings College London, London, UK; Department of Neurology, University of California, San Francisco CA, USA.Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Craniofacial Pain Center, Tufts University School of Dental Medicine, Boston, MA, USA; Headache and Face Pain Program, Tufts Medical Center, Boston, MA, USA.Eli Lilly and Company, Indianapolis, IN, USA.Arteaus Therapeutics, Cambridge, MA, USA.Arteaus Therapeutics, Cambridge, MA, USA.

Pub Type(s)

Clinical Trial, Phase II
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25127173

Citation

Dodick, David W., et al. "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, vol. 13, no. 9, 2014, pp. 885-92.
Dodick DW, Goadsby PJ, Spierings EL, et al. 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. Lancet Neurol. 2014;13(9):885-92.
Dodick, D. W., Goadsby, P. J., Spierings, E. L., Scherer, J. C., Sweeney, S. P., & Grayzel, D. S. (2014). 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, 13(9), 885-92. https://doi.org/10.1016/S1474-4422(14)70128-0
Dodick DW, et al. 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. Lancet Neurol. 2014;13(9):885-92. PubMed PMID: 25127173.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Dodick,David W, AU - Goadsby,Peter J, AU - Spierings,Egilius L H, AU - Scherer,Joel C, AU - Sweeney,Steven P, AU - Grayzel,David S, Y1 - 2014/08/10/ PY - 2014/8/16/entrez PY - 2014/8/16/pubmed PY - 2014/12/18/medline SP - 885 EP - 92 JF - The Lancet. Neurology JO - Lancet Neurol VL - 13 IS - 9 N2 - BACKGROUND: Migraine remains poorly treated, with few effective preventive drugs available. We assessed the safety and efficacy of LY2951742, a fully humanised monoclonal antibody to calcitonin gene-related peptide, for migraine prevention. METHODS: We did a randomised, double-blind, placebo-controlled, phase 2 proof-of-concept study at 35 centres in the USA. Patients aged 18-65 years with four to 14 migraine headache days per month were randomly assigned (1:1) to LY2951742 or placebo by a computerised randomisation scheme. LY2951742 (150 mg) or placebo were given as a subcutaneous injection once every 2 weeks for 12 weeks. The primary endpoint was the mean change in number of migraine headache days per 28-day period assessed at 9-12 weeks. Safety was assessed over 24 weeks, including the 12-week treatment period and the subsequent 12 weeks after study drug administration. Patients and treating investigators were masked to treatment allocation. Analyses were by intention to treat. A mixed-effects model of repeated measures was used, including patient baseline value, treatment, visit, and treatment-by-visit interaction as fixed effects, and patients as random effects. Safety measures were analysed according to the treatment received. This study has been completed and is registered with ClinicalTrials.gov, NCT01625988. FINDINGS: Between July 31, 2012, and Sept 18, 2013, 218 patients were randomly assigned to LY2951742 (n=108, but one patient withdrew before treatment) or placebo (n=110). The mean change from baseline to week 12 in the number of migraine headache days was -4·2 (SD 3·1; 62·5% decrease) in the LY2951742 group compared with -3·0 (SD 3·0; 42·3% decrease) in the placebo group (least-squares mean difference -1·2, 90% CI -1·9 to -0·6; p=0·0030). Adverse events that occurred more frequently with LY2951742 than with placebo included injection site pain, erythema, or both (21 [20%] of 107 vs seven [6%] of 110), upper respiratory tract infections (18 [17%] vs ten [9%]), and abdominal pain (six [6%] vs three [3%]). There were two serious adverse events reported in the treatment arm and four in the placebo arm, none of which were deemed to be related to the study drug. INTERPRETATION: These results provide preliminary evidence that LY2951742 might be beneficial in migraine prevention and provide support for the role of calcitonin gene-related peptide in the pathogenesis of migraine. Further controlled studies are needed to assess the safety and efficacy of monoclonal calcitonin gene-related peptide antibodies for the preventive treatment of migraine. FUNDING: Arteaus Therapeutics. SN - 1474-4465 UR - https://www.unboundmedicine.com/medline/citation/25127173/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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1474-4422(14)70128-0 DB - PRIME DP - Unbound Medicine ER -