Additional
Information
Study
REGAIN had a 3 month, double-blind, placebo-controlled treatment
period followed by a 9 month open-label extension. Approximately
15 % of the patients continued concurrent treatment with
topiramate or propranolol as allowed by the protocol for prophylaxis
of migraine.1
Please
note that the results of a maintenance dose of 240 mg galcanezumab
once monthly are also included in this response. Even though this
dose has been tested in pivotal studies, it has not been approved and
therefore is not recommended.
Concomitant
Use With Migraine Preventives in a Phase 3 Study for Chronic Migraine
An
overview of migraine phase 3 clinical trials are provided in
Appendix: Clinical Trial Information
In
general, patients were not allowed to continue on prior migraine
prophylactic therapies.2,3
However, up to 33% of patients in the chronic migraine
prevention trial were allowed to continue migraine prophylactic
treatment with either topiramate or propranolol if
the
patient has been on a stable dose for at least 2 months prior to the
prospective baseline period, and
dosing
will remain stable throughout the double-blind treatment period.2,3
In
this study, 14.6% of patients were concomitantly using either
topiramate (10.1%) or propranolol (4.5%) for migraine prophylaxis.2,3
Safety
Analysis for Concomitant Prophylaxis Subgroups
The
safety profile, including common TEAEs, vital signs, and weight, by
baseline concurrent prophylaxis use subgroup (yes/no) was analyzed to
assess whether there was a differential treatment effect of
galcanezumab compared to placebo among the subgroup of patients with
concurrent prophylaxis use versus the subgroup of patients without
concurrent prophylaxis use.2
Vital
Sign Changes by Concomitant Prophylaxis Subgroup
Analysis
of vital signs and weight by concurrent prophylaxis subgroups
(yes/no) found no interaction between concurrent prophylaxis use and
treatment group on
pulse,
temperature,
or
weight.2
There
was a statistically significant interaction between concomitant
prophylaxis and treatment group on both SBP and DBP.2
For
SBP, the difference in overall least squares mean change between the
galcanezumab 240-mg dose group and placebo were
-3.62
mm Hg for the “yes” concurrent prophylaxis use group
(p=.026 vs placebo), and
-0.03
mm Hg for the “no” concurrent prophylaxis group.2
A
similar pattern was observed for DBP, with a least squares mean
difference between the galcanezumab 240-mg dose group and placebo of
-4.26
mm Hg for the “yes” concurrent prophylaxis use group
(p<.001 vs placebo), and
0.20
mm Hg for the “no” concurrent prophylaxis group.2
Results
should be interpreted with caution due to the relatively small sample
size for the concurrent prophylaxis use "yes" group
(n=157).2
Although
the SBP and DBP decreases in patients with concomitant prophylaxis
was statistically significant for the group mean change analysis,
only 3 of the 80 galcanezumab-treated patients (all received
galcanezumab 240 mg) had a treatment-emergent decrease in either SBP
or DBP or both at 1 time point. Of the 3 patients,
2
were receiving concomitant propranolol, and
1
was receiving concomitant topiramate.2
The
decrease was not sustained and did not result in an AE of hypotension
being reported. Therefore, these findings were likely not clinically
meaningful.2
Treatment-Emergent
Adverse Events by Concomitant Prophylaxis Subgroup
Subgroup
analysis of common TEAEs by baseline concurrent prophylaxis use did
not indicate any clinically meaningful differences in incidence of
these AEs in patients with or without concurrent prophylaxis use.2,4
Based
on these results, concomitant use of prophylaxis does not have an
effect on the safety of galcanezumab.2
Efficacy
Analysis for Concomitant Prophylaxis Subgroups
An
analysis of mean change from baseline in the number of monthly
migraine headache days by concomitant prophylaxis use for the subset
of patients who were using concomitant topiramate or propranolol
showed an overall mean reduction in the number of monthly migraine
headache days across months 1 to 3 (Table
1).2
Table
1. Change From Baseline in Number of Monthly Migraine Headache Daysa
by Concurrent Prophylaxis Use2
|
N
|
Changeb
in Migraine Headache Days
|
P
Value vs PBO
|
Yes
|
PBO
|
80
|
-1.41
|
N/A
|
GMB
120 mg
|
37
|
-2.27
|
.422
|
GMB
240 mg
|
41
|
-2.58
|
.242
|
No
|
PBO
|
458
|
-3.34
|
N/A
|
GMB
120 mg
|
236
|
-5.66
|
<.001
|
GMB
240 mg
|
233
|
-5.42
|
<.001
|
Abbreviations:
GMB = galcanezumab; N/A = not applicable; PBO = placebo.
a
Across months 1 to 3.
b
Least squares mean change from baseline.
There
was no statistically significant treatment-by-subgroup interaction in
concurrent prophylaxis users.2
This subgroup was small, with insufficient power to detect a
difference versus placebo. However, the differences observed between
galcanezumab and placebo were directionally consistent, although
smaller in magnitude, than those observed in patients not receiving
concomitant prophylaxis.2
For
patients not using concomitant topiramate or propranolol, the overall
mean reduction in the number of monthly migraine headache days across
months 1 to 3 is also summarized in Table
1.2
Although
galcanezumab did not seem to provide as much benefit to patients
receiving concomitant prophylaxis as it did to those given
monotherapy, some improvements were observed. However, this subgroup
was small, and these results may be confounded by selection bias.
This population comprised patients who were already taking
concomitant prophylaxis and yet agreed to participate in a clinical
trial, which may signal that they were more difficult to treat.2
A
review of this population at baseline showed that they had had
migraine diagnoses for longer than the rest of the population
(average of 23.0 years for patients taking concomitant prophylaxis
versus 20.8 years for patients not taking it), also indicating that
they may be a difficult to treat group.2
Concomitant
Use With Migraine Preventives in Phase 3 Studies for Episodic
Migraine
Use
of migraine preventive medications was not allowed in the episodic
migraine clinical trials.5,6
The
decision to administer galcanezumab in combination with migraine
preventives must be based on the clinical judgment of the prescribing
healthcare practitioner after careful consideration of the patient's
risk factors as well as the risks and benefits of treatment. The
decision remains at the discretion of the prescribing physician.
Therapeutic
Indication
Galcanezumab
is indicated for the prophylaxis of migraine in adults who have at
least 4 migraine days per month.1
The
recommended dose is 120 mg galcanezumab injected subcutaneously once
monthly, with a 240 mg loading dose as the initial dose.1
References
1.
Emgality [summary of product characteristics]. Eli Lilly Nederland
B.V., The Netherlands.
2.
Data on file, Eli Lilly and Company and/or one of its subsidiaries.
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.
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 Neurol. 2020;20(1):25.
http://dx.doi.org/10.1186/s12883-020-1609-7.
Published correction appears in BMC Neurol. 2020;20(1):90.
http://dx.doi.org/10.1186/s12883-020-01675-7
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.
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
Glossary
AE =
adverse event
DBP
= diastolic blood pressure
SBP
= systolic blood pressure
TEAE
= treatment-emergent adverse event
▼ 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.
Appendix:
Clinical Trial Information
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),5,6
and
chronic
migraine (REGAIN).3
The
studies had a duration of
6
months for prevention of episodic migraine,5,6
and
3
months for prevention of chronic migraine, with an optional 9-month
open-label extension phase.3
Patients
were randomized at the beginning of double-blind treatment in a 2:1:1
ratio to receive monthly subcutaneous injections of
placebo
galcanezumab
120 mg with a loading dose of 240 mg, or
galcanezumab
240 mg.3,5,6
The
primary endpoint was the overall mean change from baseline in the
number of monthly migraine headache days over
6
months for episodic migraine, and
3
months for chronic migraine.3,5,6
In
these studies, the 240 mg galcanezumab dose was not observed to be
more efficacious overall than the 120 mg dose.2
Therefore, the recommended dose is 120 mg injected
subcutaneously once monthly, with a 240 mg loading dose as the
initial dose.