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).

What is the cardiovascular safety profile of Emgality® ▼ (galcanezumab)?

There were no significant differences in the cardiovascular (CV) safety profiles of galcanezumab and placebo in the study populations. The populations excluded patients with recent acute CV events and those at serious CV risk.

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Phase-3-Trials: Cardiovascular TEAEs and SAEs Similar Between Galcanezumab and Placebo

The incidence of cardiovascular adverse events was low, and there were no significant differences between the galcanezumab and placebo groups in the frequency of cardiovascular

Likely Cardiovascular Treatment-Emergent Adverse Events:a Placebo-Controlled Group2

 

PBO
N=1628
n (%)

GMB Pooledb
N=1601
n (%)

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.

Likely Cardiovascular Serious Adverse Events:a Placebo-Controlled Group2

 

PBO
N=1628
n (%)

GMB Pooledb
N=1601
n (%)

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.

Phase-3-Trials: Blood Pressure Changes Similar Between Galcanezumab and Placebo

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

Categorical Increases in Blood Pressure:a Placebo-Controlled Group2

 

PBO

GMB Pooledb

Safety population

N=1582
n (%)

N=1580
n (%)

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

Sustained Increases in Blood Pressure:a Placebo-Controlled Group2

 

PBO

GMB Pooledb

Safety population

N=1537
n (%)

N=1544
n (%)

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.

Phase-3-Trials: Increased Pulse of Heart Rate Similar Between Galcanezumab and Placebo

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 (Categorical Increases in Pulse: Placebo-Controlled Group).2

Categorical Increases in Pulse:a Placebo-Controlled Group2,3

 

PBO
n/N (%)

GMB Pooledb
n/N (%)

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 (Sustained Increases in Pulse: Placebo-Controlled Group).2

Sustained Increases in Pulse:a Placebo-Controlled Group2

 

PBO
n/N (%)

GMB Pooledb
n/N (%)

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.

Phase-3- and Phase-2-Trials: Cardiovascular TEAEs and SEAs Do Not Increase With Exposure Up To 12 Months

We evaluated longer-term exposure to galcanezumab with an all-galcanezumab group, composed of all 9 phase-2- or phase-3-studies up to 12 months in duration and with 1799.4 patient-years of exposure.2

We do not have data beyond 12 months of galcanezumab exposure.3

The frequency of cardiovascular treatment-emergent or serious adverse events did not increase with longer term exposure (Cardiovascular Treatment-Emergent and Serious Adverse Events With Longer Term Exposure).1

Cardiovascular Treatment-Emergent and Serious Adverse Events With Longer Term Exposure2

 

All-GMB Group
n (%)


TEAEa

N=2882

Patients with ≥1 CV TEAE

142 (4.9)

Cardiac arrhythmias

22 (0.8)

Cardiac failure

1 (0.0)

CNS vascular disorders

4 (0.1)

Embolic and thrombotic events

8 (0.3)

Hypertension

49 (1.7)

Ischemic heart disease

3 (0.1)

Torsades de pointes/QT prolongation

5 (0.2)

SAEa

N=2889

Patients with ≥1 CV SAE

8 (0.3)b

Myocardial infarction

2 (0.1)

Pulmonary embolism

1 (0.0)

Transient ischemic attack

1 (0.0)

Deep vein thrombosis

0 (0.0)

Atrial fibrillation

1 (0.0)

Cerebral ischemia

1 (0.0)

Palpitation

1 (0.0)

Angina unstable

1 (0.0)

Cardiac failure congestive

1 (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; SAE = serious adverse event; TEAE = treatment-emergent adverse event.

aEach preferred term represents the narrow scope terms only.

bOne event each of myocardial infarction and unstable angina occurred in the same patient.

Postmarketing Reports of Adverse Events 

Postmarketing spontaneous reports in the Eli Lilly and Company spontaneous adverse events database through 27 March 2021 have the following definitions of incidence

  • Very Rarely reported, defined as an estimated reporting rate of <0.01% 
  • Rarely reported, defined as an estimated reporting rate of ≥0.01% and <0.1% 3

We would like to make you aware that postmarketing data do not necessarily represent the rate of occurrence of an adverse event in a treated population, but they represent a reporting rate of a particular adverse event to the company. Spontaneous reporting of adverse events 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.4

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.4

Postmarketing Reports Related to Increased Blood Pressure

  • Blood pressure increased and hypertension were rarely reported, and
  • Blood pressure abnormal, blood pressure fluctuation, blood pressure diastolic increased, and blood pressure systolic increased were very rarely reported.3

Postmarketing Reports Related to Increased Heart Rate or Palpitations

  • Palpitations and heart rate increased were rarely reported, and
  • Heart rate abnormal, heart rate irregular, sinus tachycardia, supraventricular tachycardia, tachycardia, and ventricular tachycardia were very rarely reported.3

Phase-3-Trials: Description of Analysis of Cardiovascular Adverse Events

We evaluated the CV adverse event profile of galcanezumab with integrated data from a total of 5 placebo-controlled studies with up to 6 months of galcanezumab exposure (573.4 patient-years).1

We pooled galcanezumab doses prior to the analysis, as they were different across the studies.1

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.

This integrated analysis found that the incidence of cardiovascular treatment-emergent adverse events and serious adverse events was low and did not differ between the galcanezumab and placebo groups.1 These findings were consistent with, and expand upon, an earlier analysis of cardiovascular safety based on data from 3 placebo-controlled studies.5

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://n.neurology.org/content/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.

4Goldman 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

5Oakes 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

Evaluation of Cardiovascular Safety - Definitions and Search Strategy

Potential treatment-emergent cardiovascular 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 treatment-emergent adverse event potentially cardiovascular in nature was generated from these SMQs.3

Medical Dictionary for Regulatory Activities SMQ ‘narrow’ terms included preferred terms that are highly likely to represent the condition of interest.3

The SMQs analyzed to identify potential treatment-emergent cardiovascular events were3,5

  • 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 cardiovascular treatment-emergent adverse events identified by these preferred terms was then medically reviewed to determine if the terms identified represented likely cardiovascular treatment-emergent adverse events. 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 cardiovascular treatment-emergent adverse events are discussed herein unless otherwise specified.3,5

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: 30 January 2020


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