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Emgality ® (galcanezumab)
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What is the cardiovascular safety profile of Emgality® (galcanezumab)?
The cardiovascular (CV) adverse event (AE) profile of galcanezumab was evaluated using integrated data from migraine prevention studies.
Table of Contents
Were cardiovascular TEAEs and SAEs similar between galcanezumab and placebo in phase 3 trials?
The incidence of cardiovascular adverse events (CV AEs) was low, and there were no significant differences between the galcanezumab and placebo groups in the frequency of cardiovascular
|
PBO |
GMB Pooledb |
Patients with ≥1 CV TEAE |
53 (3.3) |
50 (3.1) |
Cardiac arrhythmias |
6 (0.4) |
7 (0.4) |
Cardiac failure |
1 (0.1) |
0 (0.0) |
Cardiomyopathy |
0 (0.0) |
0 (0.0) |
CNS vascular disorders |
0 (0.0) |
1 (0.1) |
Embolic and thrombotic events |
4 (0.3) |
4 (0.3) |
Hypertension |
21 (1.3) |
19 (1.2) |
Ischemic heart disease |
1 (0.1) |
2 (0.1) |
Pulmonary hypertension |
0 (0.0) |
0 (0.0) |
Torsades de pointes/QT prolongation |
2 (0.1) |
2 (0.1) |
Abbreviations: CNS = central nervous system; CV = cardiovascular; GMB = galcanezumab; N = number of patients in the analysis population; n = number of patients within each specific category; PBO = placebo; TEAE = treatment-emergent adverse event.
aEach preferred term represents the narrow scope terms only.
bAll galcanezumab doses combined.
|
PBO |
GMB Pooledb |
Patients with ≥1 CV SAE |
3 (0.2) |
4 (0.3) |
Myocardial infarction |
1 (0.1) |
1 (0.1) |
Pulmonary embolism |
1 (0.1) |
1 (0.1) |
Transient ischemic attack |
0 (0.0) |
1 (0.1) |
Deep vein thrombosis |
1 (0.1) |
0 (0.0) |
Atrial fibrillation |
0 (0.0) |
1 (0.1) |
Abbreviations: CV = cardiovascular; GMB = galcanezumab; N = number of patients in the analysis population; n = number of patients within each specific category; PBO = placebo; SAE = serious adverse event.
aEach preferred term represents the narrow scope terms only.
bAll galcanezumab doses combined.
Incidence of CV TEAEs or SAEs were not affected by longer treatment duration
The frequency of CV TEAEs or SAEs did not increase with longer term exposure (), which is represented by the all-galcanezumab group.1
|
All-GMB Group |
PBO |
GMB Pooleda |
Placebo-Controlled Group |
|||
TEAEb |
N=2882 |
N=1628 |
N=1601 |
Patients with ≥1 CV TEAE |
142 (4.9) |
53 (3.3) |
50 (3.1) |
Cardiac arrhythmias |
22 (0.8) |
6 (0.4) |
7 (0.4) |
Cardiac failure |
1 (0.0) |
1 (0.1) |
0 (0.0) |
CNS vascular disorders |
4 (0.1) |
0 (0.0) |
1 (0.1) |
Embolic and thrombotic events |
8 (0.3) |
4 (0.3) |
1 (0.1) |
Hypertension |
49 (1.7) |
21 (1.3) |
19 (1.2) |
Ischemic heart disease |
3 (0.1) |
1 (0.1) |
2 (0.1) |
Torsades de pointes/QT prolongation |
5 (0.2) |
2 (0.1) |
2 (0.1) |
SAEb |
N=2889 |
N=1628 |
N=1601 |
Patients with ≥1 CV SAE |
8 (0.3)c |
3 (0.2) |
4 (0.3) |
Myocardial infarction |
2 (0.1) |
1 (0.1) |
1 (0.1) |
Pulmonary embolism |
1 (0.0) |
1 (0.1) |
1 (0.1) |
Transient ischemic attack |
1 (0.0) |
0 (0.0) |
1 (0.1) |
Deep vein thrombosis |
0 (0.0) |
1 (0.1) |
0 (0.0) |
Atrial fibrillation |
1 (0.0) |
0 (0.0) |
1 (0.1) |
Cerebral ischemia |
1 (0.0) |
0 (0.0) |
0 (0.0) |
Palpitation |
1 (0.0) |
0 (0.0) |
0 (0.0) |
Angina unstable |
1 (0.0) |
0 (0.0) |
0 (0.0) |
Cardiac failure congestive |
1 (0.0) |
0 (0.0) |
0 (0.0) |
Abbreviations: CNS = central nervous system; CV = cardiovascular; GMB = galcanezumab; N = number of patients in the analysis population; n = number of patients within each specific category; PBO = placebo; SAE = serious adverse event; TEAE = treatment-emergent adverse event.
aAll galcanezumab doses combined.
bEach preferred term represents the narrow scope terms only.
cOne event each of myocardial infarction and unstable angina occurred in the same patient.
Were the changes in blood pressure similar between galcanezumab and placebo in the phase 3 trials?
Categorical increases in blood pressure similar to placebo
Categorical blood pressure increases were defined as
- treatment-emergent high ≥140 mm Hg with ≥20 mm Hg increase in systolic blood pressure, or
- treatment-emergent high ≥90 mm Hg with ≥10 mm Hg increase in diastolic blood pressure.2
The percentages of patients with a categorical increase in systolic or diastolic blood pressure at any time post baseline were
- similar between treatment groups (), and
- not affected by elevated blood pressure at baseline.2
|
PBO |
GMB Pooledb |
Safety population |
N=1582 |
N=1580 |
SBP |
47 (3.0) |
51 (3.2) |
DBP |
107 (6.8) |
122 (7.7) |
Safety population with elevated SBP or DBP at baseline |
n/N (%) |
n/N (%) |
SBP |
2/100 (2.0) |
2/91 (2.2) |
DBP |
17/153 (11.1) |
12/138 (8.7) |
Abbreviations: DBP = diastolic blood pressure; GMB = galcanezumab; PBO = placebo; SBP = systolic blood pressure.
aCategorical increase in SBP was defined as treatment-emergent high ≥140 mm Hg with ≥20 mm Hg increase. Categorical increase in DBP was defined as treatment-emergent high ≥90 mm Hg with ≥10 mm Hg increase.
bAll galcanezumab doses combined.
Sustained increases in blood pressure similar to placebo
Sustained blood pressure increases were defined as
- elevation ≥140 mm Hg with ≥20 mm Hg increase in systolic blood pressure for 2 consecutive office visits, or
- elevation ≥90 mm Hg with ≥10 mm Hg increase in diastolic blood pressure for 2 consecutive office visits.2
The percentages of patients with a sustained increase in systolic or diastolic blood pressure at any time post baseline were
- similar between treatment groups (), and
- not affected by the presence of elevated blood pressure at baseline.2
|
PBO |
GMB Pooledb |
Safety population |
N=1537 |
N=1544 |
SBP |
7 (0.5) |
3 (0.2) |
DBP |
17 (1.1) |
19 (1.2) |
Safety population with elevated SBP or DBP at baseline |
n/N (%) |
n/N (%) |
SBP |
0/96 (0.0) |
0/89 (0.0) |
DBP |
2/146 (1.4) |
0/133 (0.0) |
Abbreviations: DBP = diastolic blood pressure; GMB = galcanezumab; PBO = placebo; SBP = systolic blood pressure.
aSustained elevation in blood pressure was defined as elevation ≥140 mm Hg with ≥20 mm Hg increase in SBP for 2 consecutive office visits, or elevation ≥90 mm Hg with ≥10 mm Hg increase in DBP for 2 consecutive office visits.
bAll galcanezumab doses combined.
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Was the increase in pulse or heart rate similar between galcanezumab and placebo in the phase 3 trials?
Categorical increases in pulse similar to placebo
Categorical increase in pulse was defined as treatment-emergent high >100 bpm with ≥15 bpm increase from baseline.2
The incidence of patients with categorical increase in pulse was low and similar between placebo and galcanezumab, and was not affected by presence of elevated pulse at baseline ().2
|
PBO |
GMB Pooledb |
Safety population |
34/1582 (2.1) |
31/1580 (2.0) |
Safety population with elevated pulse at baselinec |
1/14 (7.1) |
0/7 (0.0) |
Abbreviations: GMB = galcanezumab; PBO = placebo.
aDefined as treatment-emergent high >100 bpm with ≥15 bpm increase from baseline.
bAll galcanezumab doses combined.
cPulse >100 bpm at baseline was considered elevated.
Sustained increases in pulse similar to placebo
Sustained increase in pulse was defined as elevation >100 bpm with ≥15 bpm increase for 2 consecutive office visits.2
The percentages of patients with a sustained increase in pulse at any time post baseline were similar between treatment groups, regardless of if they had elevated pulse at baseline ().2
|
PBO |
GMB Pooledb |
Safety population |
1/1537 (0.1) |
2/1544 (0.1) |
Safety population with elevated pulse at baseline |
0/13 (0.0) |
0/7 (0.0) |
Abbreviations: GMB = galcanezumab; PBO = placebo.
aDefined as elevation >100 bpm with ≥15 bpm increase for 2 consecutive office visits.
bAll galcanezumab doses combined.
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How were cardiovascular adverse events analysed in the phase 3 trials?
The cardiovascular (CV) adverse event (AE) profile of galcanezumab was evaluated using integrated data from migraine prevention studies.1
Galcanezumab doses were pooled prior to the analysis, as galcanezumab doses were different across studies.1
These studies were analyzed into 2 groups with the
- placebo-controlled group composed of 5 placebo-controlled studies with up to 6 months of galcanezumab exposure (with 573.4 patient-years of exposure), and
- all-galcanezumab group composed of all 9 galcanezumab studies (with 1799.4 patient-years of exposure).1
Longer-term exposure to galcanezumab was evaluated using the all-galcanezumab group (Incidence of CV TEAEs or SAEs were not affected by longer treatment duration).2
In these studies, the majority of patients were female (>75%) and Caucasian (>75%), with a mean age of 41 to 42 years.2
Please find cardiovascular safety definitions and the search strategy used to identify likely cardiovascular treatment-emergent events in the clinical studies in the Appendix.
The findings in these integrated analyses were consistent with, and expand upon, an earlier analysis of cardiovascular safety based on data from 3 placebo-controlled studies.4
References
1Oakes T, Kovacs R, Rosen N, et al. Evaluation of cardiovascular risks in patients treated with longer-term exposure to galcanezumab. Neurology. 2021;96(15 Suppl):2344. https://doi.org/10.1212/WNL.96.15_supplement.2344
2Oakes TM, Kovacs R, Rosen N, et al. Evaluation of cardiovascular risks in patients treated with longer-term exposure to galcanezumab. Poster presented at: 73rd American Academy of Neurology Meeting (AAN Virtual); April 17-22, 2021.
3Data on file, Eli Lilly and Company and/or one of its subsidiaries.
4Oakes 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
Appendix
Definitions and search strategy related to cardiovascular safety in the galcanezumab clinical studies
Potential treatment-emergent CV events were identified using the Medical Dictionary for Regulatory Activities (MedDRA) standard MedDRA queries (SMQ) listed below; only narrow term events are shown in the results. A listing of patients having a TEAE potentially CV in nature was generated from these SMQs.3
The MedDRA SMQ ‘narrow’ terms included preferred terms (PTs) that are highly likely to represent the condition of interest.3
The SMQs analyzed to identify potential treatment-emergent CV events were3,4
- Cardiac arrhythmias (includes sub-SMQs; SMQ 20000049)
- Cardiac failure (SMQ 20000004)
- Cardiomyopathy (SMQ 20000150)
- Central nervous system vascular disorders (includes sub-SMQs; SMQ 20000060)
- Embolic and thrombotic events (includes sub-SMQs; SMQ 20000081)
- Hypertension (SMQ 20000147)
- Ischemic heart disease (includes sub-SMQs; SMQ 20000043)
- Pulmonary hypertension (SMQ 20000130), and
- Torsades de pointes/QT prolongation (SMQ 20000001).
The list of potential CV TEAEs identified by these PTs was then medically reviewed to determine if the terms identified represented likely CV TEAEs. The medical review was conducted by an Eli Lilly and Company physician with clinical trial medical data review experience who was blinded to study treatment. Only those events that were judged medically to represent likely CV TEAEs are discussed herein unless otherwise specified.3,4
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Date of Last Review: 05 January 2024