Detailed
Information
Withdrawal
and Rebound During Post-Treatment Period in the Phase 3 Migraine
Prevention Studies
Post
TEAEs related to withdrawal and rebound were evaluated for each of
the phase 3 migraine prevention trials mentioned below.1,2
There
was no evidence of withdrawal or rebound following galcanezumab
discontinuation after evaluating AEs during the post-treatment
period.1,2
A
review of withdrawal and rebound event terms did not show any pattern
of TEAEs that would indicate any withdrawal potential for
galcanezumab.1
Many
reported event terms were
During
the post-treatment phase for the phase 3 clinical trials for the
prevention of episodic and chronic migraine, there were 17 patients
across all treatment groups who reported the post TEAE of
headache or migraine.1,2
Of
the 17 patients there were
3
galcanezumab-treated patients who reported the PT of headache
11
galcanezumab-treated patients who reported the PT of migraine, and
2
placebo-treated patient who reported the PT of headache, and
1
placebo-treated patient who reported the PT of migraine.1,2
From
the available information for these patients, these events likely
represented a recurrence of their pre-existing headache
disorder. Thus, this review of AEs from galcanezumab clinical
studies provides no evidence for any potential for withdrawal or
rebound following discontinuation of galcanezumab.1
Description
of Analysis Set
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),3,4
and
chronic
migraine (REGAIN).5
The
studies had a duration of
6
months for prevention of episodic migraine,3,4
and
3
months for prevention of chronic migraine, with an optional 9-month
open-label extension phase.5
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
The
recommended dose is 120 mg galcanezumab injected subcutaneously once
monthly, with a 240 mg loading dose as the initial dose.6 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.
Galcanezumab
has also been studied in a phase 3, open-label, 12-month safety study
(CGAJ) for the prevention of episodic or chronic migraine.7
In
CGAJ, patients were randomized to either galcanezumab 120 mg (with
240-mg loading dose) or galcanezumab 240 mg monthly.7
Please
note that the results of a maintenance dose of 240 mg galcanezumab
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.
There
was a 4-month post treatment (washout) period following the
6-month
double-blind treatment period in EVOLVE-1 and EVOLVE-23,4
9-month
open-label extension period in REGAIN5,
and
12-month
open-label treatment period in CGAJ.7
References
1.
Data on file, Eli Lilly and Company and/or one of its subsidiaries.
2.
Stauffer VL, Wang S, Voulgaropoulos M, et al. Effect of galcanezumab
following treatment cessation in patients with migraine: results from
2 randomized phase 3 trials. Headache. 2019;59(6):834-847.
http://dx.doi.org/10.1111/head.13508
3.
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
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.
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
6.
Emgality [summary of product characteristics]. Eli Lilly Nederland
B.V., The Netherlands.
7.
Camporeale A, Kudrow D, Sides R, et al. A phase 3, long-term,
open-label safety study of galcanezumab in patients with migraine.
BMC Neurology. 2018;18(1):188.
http://dx.doi.org/10.1186/s12883-018-1193-2
Glossary
AE =
adverse event
PT =
preferred term
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.