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Emgality ® ▼ (galcanezumab)
This information is intended for UK registered healthcare professionals only as a scientific exchange in response to your search for information. For current prescribing information for all Lilly products, including Summaries of Product Characteristics, Patient Information Leaflets and Instructions for Use, please visit: www.medicines.org.uk (England, Scotland, Wales) or www.emcmedicines.com/en-GB/northernireland/ (Northern Ireland).
Can Emgality® (galcanezumab) be used in patients with a history of CNS vascular events?
The phase 3 studies included patients with a history of CNS vascular events. No reports of CNS vascular TEAEs in the patients with a history of CNS vascular events were observed.
Content overview
Information from the label
Patients with recent acute cardiovascular events (including MI, unstable angina, CABG, stroke, DVT) and/or those deemed to be at serious cardiovascular risk were excluded from the galcanezumab clinical trials.1
Evaluation of CNS vascular events in Phase 3 migraine prevention clinical trials
The EVOLVE-1, EVOLVE-2, and REGAIN studies were the pivotal studies and safety results have been integrated resulting in a pooled analysis of 2886 adult patients.2
A total of 1435 patients received monthly doses of galcanezumab (120 mg or 240 mg) administered subcutaneously.2
Additional details on migraine prevention studies are available in the section in Appendix: Migraine prevention studies.
Results from the phase 3 open-label safety study (CGAJ) are provided to supplement the primary integrated safety analysis from the phase 3 migraine prevention clinical trials.
Evaluation of safety by baseline cardiovascular risk was not completed in the CONQUER study; however, information is provided regarding central nervous system (CNS) vascular disorders where relevant.
In the 12-month open-label safety study (CGAJ), a total of 270 adult patients received monthly doses of galcanezumab (120 or 240 mg).3
In the CONQUER study, 462 adult patients were enrolled, with 232 patients receiving monthly doses of galcanezumab 120 mg.4
What were the baseline CNS vascular disorder characteristics of patients included in clinical studies?
Exclusion criteria
Patients were excluded from the phase 3 migraine prevention clinical trials if they had
- a stroke within 6 months of screening (EVOLVE-1, CGAJ, and CONQUER)
- a lifetime history of stroke (EVOLVE-2 and REGAIN), or
- a history or presence of any other medical illness, including, but not limited to cardiovascular, or any clinically significant laboratory abnormality, that in the judgment of the investigator indicates a medical problem that would preclude study participation.5,6
CNS vascular disorders at baseline
Between 17% and 19% of all patients across the galcanezumab and placebo treatment groups in EVOLVE-1, EVOLVE-2, and REGAIN were in the cardiovascular disease risk "yes" subgroup, or had a comorbid cardiovascular condition or risk factor at baseline.6
The definition of cardiovascular risk is available in the section in Appendix: Definition of cardiovascular disease risk.
Baseline CNS Vascular Disorders Among Patients in the Cardiovascular Disease Risk "Yes" Group - EVOLVE-1, EVOLVE-2, and REGAIN provides baseline CNS vascular disorders among patients in the cardiovascular disease risk "yes" group.5
CNS Vascular Disorders (SMQ) |
PBO |
GMB 120 mg |
GMB 240 mg |
GMB Pooled |
Carotid arteriosclerosisa |
0 (0.0) |
1 (0.81) |
0 (0.0) |
1 (0.40) |
Carotid artery diseasea |
0 (0.0) |
0 (0.0) |
1 (0.81) |
1 (0.40) |
Carotid artery stenosisa |
1 (0.37) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
Cerebral artery stenosisa |
0 (0.0) |
1 (0.81) |
0 (0.0) |
1 (0.40) |
Cerebral infarctiona |
1 (0.37) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
CVAa |
2 (0.74) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
Ischemic strokea |
0 (0.0) |
0 (0.0) |
1 (0.81) |
1 (0.40) |
TIAa |
5 (1.86) |
0 (0.0) |
1 (0.81) |
1 (0.40) |
Abbreviations: CNS = central nervous system; CVA = cerebrovascular accident; GMB = galcanezumab; MedDRA = Medical Dictionary for Regulatory Activities; PBO = placebo; SMQ = standardized MedDRA query; TIA = transient ischemic attack.
aNarrow scope preferred term.
Back to Content overview.
What CNS vascular disorder treatment-emergent adverse events were reported in patients?
Two patients among galcanezumab-treated patients reported serious CNS vascular disorder treatment-emergent adverse events (TEAEs) in EVOLVE-1, EVOLVE-2, REGAIN, and CGAJ
- one patient reported a transient ischemic attack (TIA)
- second patient reported intracranial aneurysm.5,6
Both patients were in the baseline cardiovascular disease risk "no" subgroup.5
Both events resolved and the events were deemed not to be related to galcanezumab by the primary investigators because of
Exposure-Adjusted Incidence Rates
Exposure-adjusted incidence rates (EAIRs) are a measure of whether TEAEs occur at an increased frequency with increased treatment duration.5
In the phase 3 double-blind, placebo-controlled migraine prevention clinical trials, there were no significant differences between galcanezumab treatment groups and placebo in EAIRs of CNS vascular disorder TEAEs (galcanezumab pooled 0.19; placebo 0.0). No increase was observed in the EAIRs for CNS vascular disorder TEAEs in the longer-term analysis sets up to 12 months.5
The EAIR is equal to 100 times the number of patients experiencing the event divided by event-specific total patient year-at-risk.5
Is the incidence and prevalence of TIA and ischemic stroke increased in people with migraine?
Calcitonin gene-related peptide (CGRP) is a potent microvascular vasodilator found throughout the body that is hypothesized to play a protective role in cardiovascular health.7
Epidemiology studies report that cardiovascular comorbidities and risk factors for cardiovascular disease vary with
- age
- migraine severity, and
- migraine type.8-10
Observational studies have reported increased relative risks for cardiovascular events, including ischemic stroke and TIA, in the migraine population compared to the non-migraine population.8,11-15
Incidence and Prevalence of TIA and Ischemic Stroke in People With Migraine shows the incidence and prevalence of ischemic stroke and TIA reported in epidemiology studies of people with migraine.
TIA |
Ischemic Stroke |
|
Incidence |
0.93 per 1000 patient-years8 |
1.10 per 1000 person-years (any stroke)8 |
In men (average age 51 years), crude incidence per 1000 person-years: |
||
In women ≥45 years, the age-adjusted incidence of ischemic stroke per 1000 person-years: |
||
1.17 |
||
Prevalence |
2.8% of women and 2.5% of men9 |
2.0% of women and 1.6% of men (any stroke)9 |
Abbreviation: TIA = transient ischemic attack.
Back to Content overview.
Postmarketing spontaneous reports
Through September 27, 2020, the following cerebrovascular events have been very rarely reported in the Lilly spontaneous AE database
- cerebrovascular accident
- cerebellar artery thrombosis
- ischemic stroke, and
- transient ischemic attack.5
Very rarely reported is defined as an adverse event (AE) that has been reported at an estimated rate of <.01% according to the reporting system information.5
Information is not available regarding patient baseline cardiovascular risk for these postmarketing reports.
Postmarketing data do not necessarily represent the rate of occurrence of an AE in a treated population, but they represent a reporting rate of a particular AE to the company. Spontaneous reporting of AEs can be highly variable and is not appropriately controlled clinical information on which to base an assessment of whether a particular drug product is the causal agent of an event.17
Spontaneous reporting has limited use due to
- lack of control population
- under-reporting or reporting bias, and
- missing or incomplete information regarding medical history or concomitant medications.17
Back to Content overview.
References
1Emgality [summary of product characteristics]. Eli Lilly Nederland B.V., The Netherlands.
2Bangs ME, Kudrow D, Wang S, et al. Safety and tolerability of monthly galcanezumab injections in patients with migraine: integrated results from migraine clinical studies. BMC Neurol. 2020;20(1):25. https://doi.org/10.1186/s12883-020-1609-7
3Camporeale A, Kudrow D, Sides R, et al. A phase 3, long-term, open-label safety study of galcanezumab in patients with migraine. BMC Neurol. 2018;18(1):188. http://dx.doi.org/10.1186/s12883-018-1193-2
4Mulleners WM, Kim BK, Láinez MJA, et al. Safety and efficacy of galcanezumab in patients for whom previous migraine preventive medication from two to four categories had failed (CONQUER): a multicentre, randomised, double-blind, placebo-controlled, phase 3b trial. Lancet Neurol. 2020;19(10):814-825. http://dx.doi.org/10.1016/S1474-4422(20)30279-9
5Data on file, Eli Lilly and Company and/or one of its subsidiaries.
6Oakes TM, Kovacs R, Rosen N, et al. Evaluation of cardiovascular outcomes in adult patients with episodic or chronic migraine treated with galcanezumab: data from three phase 3, randomized, double-blind, placebo-controlled EVOLVE-1, EVOLVE-2, and REGAIN studies. Headache. 2020;60(1):110-123. http://dx.doi.org/10.1111/head.13684
7Russell FA, King R, Smillie SJ, et al. Calcitonin gene-related peptide: physiology and pathophysiology. Physiol Rev. 2014;94(4):1099-1142. http://dx.doi.org/10.1152/physrev.00034.2013
8Becker C, Brobert GP, Almqvist PM, et al. Migraine and the risk of stroke, TIA, or death in the UK (CME). Headache. 2007;47(10):1374-1384. http://dx.doi.org/10.1111/j.1526-4610.2007.00937.x
9Buse DC, Reed ML, Fanning KM, et al. Cardiovascular events, conditions, and procedures among people with episodic migraine in the US population: results from the American Migraine Prevalence and Prevention (AMPP) study. Headache. 2017;57(1):31-44. http://dx.doi.org/10.1111/head.12962
10Le H, Tfelt-Hansen P, Russell MB, et al. Co-morbidity of migraine with somatic disease in a large population-based study. Cephalalgia. 2011;31(1):43-64. http://dx.doi.org/10.1177/0333102410373159
11Kurth T, Gaziano JM, Cook NR, et al. Migraine and risk of cardiovascular disease in women. JAMA. 2006;296(3):283-291. http://dx.doi.org/10.1001/jama.296.3.283
12Sacco S, Ornello R, Ripa P, et al. Migraine and risk of ischaemic heart disease: a systematic review and meta-analysis of observational studies. Eur J Neurol. 2015;22(6):1001-1011. http://dx.doi.org/10.1111/ene.12701
13Peng KP, Chen YT, Fuh JL, et al. Migraine and incidence of ischemic stroke: a nationwide population-based study. Cephalalgia. 2017;37(4):327-335. http://dx.doi.org/10.1177/0333102416642602
14Lee SY, Lim JS, Oh DJ, et al. Risk of ischaemic stroke in patients with migraine: a longitudinal follow-up study using a national sample cohort in South Korea. BMJ Open. 2019;9(4):e027701. http://dx.doi.org/10.1136/bmjopen-2018-027701
15Adelborg K, Szepligeti SK, Holland-Bill L, et al. Migraine and risk of cardiovascular diseases: Danish population based matched cohort study. BMJ. 2018;360:k96. http://dx.doi.org/10.1136/bmj.k96
16Buring JE, Hebert P, Romero J, et al. Migraine and subsequent risk of stroke in the Physicians' Health Study. Arch Neurol. 1995;52(2):129-134. http://dx.doi.org/10.1001/archneur.1995.00540260031012
17Goldman SA. Limitations and strengths of spontaneous reports data. Clin Ther. 1998;20(suppl 3):C40-C44. http://dx.doi.org/10.1016/S0149-2918(98)80007-6
18Stauffer VL, Dodick DW, Zhang Q, et al. Evaluation of galcanezumab for the prevention of episodic migraine: the EVOLVE-1 randomized clinical trial. JAMA Neurol. 2018;75(9):1080-1088. http://dx.doi.org/10.1001/jamaneurol.2018.1212
19Skljarevski V, Matharu M, Millen BA, et al. Efficacy and safety of galcanezumab for the prevention of episodic migraine: results of the EVOLVE-2 phase 3 randomized controlled clinical trial. Cephalalgia. 2018;38(8):1442-1454. http://dx.doi.org/10.1177/0333102418779543
20Detke HC, Goadsby PJ, Wang S, et al. Galcanezumab in chronic migraine: the randomized, double-blind, placebo-controlled REGAIN study. Neurology. 2018;91(24):e2211-e2221. http://dx.doi.org/10.1212/WNL.0000000000006640
Appendix
Migraine prevention studies
Galcanezumab has been studied in phase 3 randomized, double-blind, placebo-controlled studies in adult patients for the prevention of
Galcanezumab has also been studied in a phase 3, open-label, 12-month safety study for the prevention of episodic or chronic migraine.3
Summary of Study Design in the Migraine Prevention Studies summarizes the galcanezumab doses used and duration of the migraine prevention studies.
|
GMB Doses Studied |
Study Duration |
120 mg monthlyb or |
6 months, double-blind |
|
REGAIN20 |
120 mg monthlyb or |
3 months, double-blind, |
CONQUER4 |
120 mg monthlyb |
3 months, double-blind, |
CGAJ3 |
120 mg monthlyb or |
12 months, open-label |
Abbreviation: GMB = galcanezumab.
aWith the exception of study CGAJ, all studies were randomized, double-blind, and placebo-controlled.
bThe initial dose was administered as a 240-mg loading dose, followed by subsequent monthly doses of 120 mg.
Definition of cardiovascular disease risk
Patients had a baseline cardiovascular disease risk of
- "yes" if they had 1 or more conditions that were part of the patients’ medical history or preexisting conditions using narrow terms from MedDRA SMQs, and
- "no" if they did not have any of the preferred terms (PTs) in the Medical Dictionary for Regulatory Activities Standard MedDRA queries (MedDRA SMQs) as a preexisting condition or medical history event.6
The MedDRA SMQs included the following:
- ischemic heart disease (sub-SMQs: myocardial infarction and other ischemic heart disease)
- hypertension
- cardiac failure
- cardiomyopathy
- ischemic central nervous system vascular conditions
- dyslipidemia, and
- hyperglycemia/new-onset diabetes mellitus.6
▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.
Date of Last Review: 02 February 2021