Summary
Patients
with coagulopathies or clotting disorders were not explicitly
excluded from phase 3 studies.1
There
were a small number of patients with a history of these conditions
in the studies, but subgroup analyses on these conditions were not
conducted.1
Information
from the label
The
use of galcanezumab is not contra-indicated in patients with
coagulopathies or clotting disorders.2
Coagulopathies
or clotting disorders are not mentionned among the adverse events
listed in the summary of product characteristics.2
Exclusion
Criteria
Patients
with coagulopathies or clotting disorders were not explicitly
excluded from the phase 3 migraine prevention studies.1,3-5
However,
patients were excluded from participation in the galcanezumab
clinical trials if they had a history or presence of any medical
illness including, but not limited to hematologic, or any clinically
significant laboratory abnormality, that in the judgment of the
investigator, indicated a medical problem that would preclude study
participation.1
Historical
Illnesses and Preexisting Conditions in Phase 3 Studies
Phase
3 Migraine Prevention Studies
Galcanezumab
has been studied in phase 3 randomized, double-blind,
placebo-controlled studies in adult patients for the prevention of
episodic
migraine (EVOLVE-1 and EVOLVE-2),4,5
and
chronic
migraine (REGAIN).3
There
was a small number of patients with historical illnesses or
preexisting conditions related to coagulopathies or clotting
disorders in the EVOLVE-1, EVOLVE-2, and REGAIN studies: Table
1. Subgroup analyses on the baseline historical illnesses
and preexisting conditions were not conducted in these patients.1
Table
1. Summary of Historical Illness or Preexisting Conditions:
Coagulopathies and Clotting Disorders in Phase 3 Double-Blind,
Placebo-Controlled Migraine Prevention Studies1
|
Preferred
Term
|
PBO
N=1451
n
(%)
|
GMB
120 mg
N=705
n (%)
|
GMB
240 mg
N=730
n (%)
|
|
Anti-factor
V antibody positive
|
0
(0.00)
|
0
(0.00)
|
1
(0.14)
|
|
Coagulation
time shortened
|
1
(0.07)
|
0
(0.00)
|
0
(0.00)
|
|
Coagulopathy
|
1
(0.07)
|
0
(0.00)
|
0
(0.00)
|
|
Congenital
coagulopathy
|
0
(0.00)
|
0
(0.00)
|
1
(0.14)
|
|
Factor
II mutation
|
0
(0.00)
|
2
(0.28)
|
0
(0.00)
|
|
Factor
V deficiency
|
1
(0.07)
|
0
(0.00)
|
0
(0.00)
|
|
Factor
V Leiden mutation
|
3
(0.21)
|
0
(0.00)
|
1
(0.14)
|
|
Factor
VII deficiency
|
0
(0.00)
|
0
(0.00)
|
1
(0.14)
|
|
MTHFR
gene mutation
|
0
(0.00)
|
2
(0.28)
|
1
(0.14)
|
|
MTHFR
deficiency
|
1
(0.07)
|
0
(0.00)
|
0
(0.00)
|
|
Platelet
aggregation abnormal
|
1
(0.07)
|
0
(0.00)
|
0
(0.00)
|
|
Von
Willebrand's disease
|
0
(0.00)
|
1
(0.14)
|
0
(0.00)
|
Abbreviations:
GMB = galcanezumab; MTHFR = methylenetetrahydrofolate reductase; PBO
= placebo.
Note:
The recommended dose is 120 mg galcanezumab injected subcutaneously
once monthly, with a 240 mg loading dose as the initial dose .2
The results of a maintenance dose of galcanezumab 240 mg once monthly
are also described here. Even though this dose has been tested in
pivotal studies, it has not been approved and therefore is not
recommended.
Laboratory
Measures
Galcanezumab
treatment was not associated with clinically meaningful abnormalities
of chemistry or hematology in the phase 3 migraine prevention,
placebo-controlled studies.1,6
Two
galcanezumab-treated patients reported treatment-emergent adverse
events of "bleeding time prolonged" and "platelet
count increased" during double-blind treatment: Table
2. The events were mild or moderate in severity and
neither patient discontinued due to the event.1
Table
2. Treatment-Emergent Adverse Events Potentially Related to Bleeding
From the Double-Blind Treatment Phase of Phase 3 Studies1
|
Preferred
term
|
PBO
N=1628
n
(%)
|
GMB
Alla
N=1601
n
(%)
|
|
Bleeding
time prolonged
|
0
(0.00)
|
1
(0.06)
|
|
Hypercoagulation
|
1
(0.06)
|
0
(0.00)
|
|
Platelet
count increased
|
0
(0.00)
|
1
(0.06)
|
Abbreviations:
GMB = galcanezumab; PBO = placebo.
a
All galcanezumab doses combined.
Published
Literature
The
role of CGRP in platelet aggregation in rats and humans has been
evaluated in the literature.7,8
References
1.
Data on file, Eli Lilly and Company and/or one of its subsidiaries.
2.
Emgality [summary of product characteristics]. Eli Lilly Nederland
B.V., The Netherlands.
3.
Detke 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
4.
Skljarevski 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
5.
Stauffer 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
6.
Bangs ME, Kudrow D, Wang S, et al. Safety and tolerability of
monthly galcanezumab injections in patients with migraine: integrated
results from migraine studies. BMC Neurology. 2020;20(1):25.
http://dx.doi.org/10.1186/s12883-020-1609-7.
Published correction appears in BMC Neurology. 2020;20(1):90.
http://dx.doi.org/10.1186/s12883-020-01675-7
7.
Matsumoto Y, Ueda S, Matsushita S, et al. Calcitonin gene-related
peptide inhibits human platelet aggregation. Jpn Circ J.
1996;60(10):797-804. http://dx.doi.org/10.1253/jcj.60.797
8.
Booth BP, Fung HL. Regulation of in vivo whole blood aggregation in
rats by calcitonin gene related peptide. Can J Physiol Pharmacol.
1998;76(7-8):811-813. http://dx.doi.org/10.1139/cjpp-76-7-8-811
Glossary
CGRP
= calcitonin gene-related peptide
IgG
= immunoglobulin G
IgG4
= immunoglobulin G (subclass) 4
PK =
pharmacokinetics
▼ 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.