Emgality ® ▼ (galcanezumab)

This information is intended for UK registered healthcare professionals only as a scientific exchange in response to your search for information. Please refer to the link for full prescribing information: Emgality Summary of Product Characteristics (SmPC)

Emgality® ▼ (galcanezumab): Use in Patients With Comorbid Hypertension

Treatment with galcanezumab did not result in changes in cardiovascular TEAEs that were greater than placebo in patients with baseline cardiovascular disease risk factors or elevated blood pressure and pulse.

Information from the label

Patients with recent acute cardiovascular events (including MI, unstable angina, CABG, stroke, DVT) and/or those deemed to be at serious cardiovascular risk were excluded from the galcanezumab clinical trials. Patients > 65 years of age were also excluded.1

No safety data are available in these patients.1

Clinical Trial Experience

Galcanezumab has been studied in migraine prevention.2-4

Patients with comorbid CV conditions and CV risk were included in the galcanezumab phase 3 studies. However, to minimize confounding at the case level and improve interpretation of the CV data, patients with acute CV events and/or serious CV risk were excluded from the clinical studies.5

A patient had a baseline CV disease risk of

  • "yes" if they had 1 or more conditions that were part of the patients’ medical history or preexisting conditions using narrow terms from MedDRA SMQs, and 

  • "no" if they did not have any of the PTs in the MedDRA SMQs as a preexisting condition or medical history event.6

The MedDRA SMQs included: Ischemic heart disease (sub-SMQs: Myocardial infarction and Other ischemic heart disease), Hypertension, Cardiac failure, Cardiomyopathy, Ischemic central nervous system vascular conditions, Dyslipidemia, and Hyperglycemia/new-onset diabetes mellitus.6  

Hypertension was evaluated using the MedDRA SMQ Hypertension (SMQ narrow terms).5

Use in Patients With Comorbid Hypertension or Elevated Baseline Blood Pressure and Pulse

The CV safety profile of galcanezumab was evaluated in phase 3 randomized, double-blind, placebo-controlled studies in adult patients for the prevention of

  • episodic migraine (EVOLVE-1 and EVOLVE-2; 6 months),2,3 and

  • chronic migraine (REGAIN; 3 months).4

Note: The recommended dose is 120 mg galcanezumab injected subcutaneously once monthly, with a 240 mg loading dose as the initial dose.1 Any other dose described here is not approved and therefore is not recommended.

Baseline Cardiovascular Disease Risk

Between 17% and 19% of all patients across the galcanezumab and placebo treatment groups in the phase 3 placebo-controlled studies were in the CV disease risk "yes" subgroup, or had a comorbid CV condition or risk factor at baseline. Of those, hypertension was the most common condition in the CV disease risk "yes" subgroup for this pooled analysis set, occurring in 41.7% of the galcanezumab pooled group and 50.2% of placebo.6 

At baseline, the percentage of patients taking antihypertensive medications in EVOLVE-1, EVOLVE-2, and REGAIN was approximately

  • 6.7% to 8.8% across all treatment groups, and

  • 30.7% to 41.6% in the CV disease risk group "yes".5,6 

Patients With a CV TEAE of Hypertension by CV Disease Risk Group

Overall, there was no significant difference between galcanezumab- and placebo- treatment groups for the hypertension SMQ. No statistically significant differences by subgroup (CV disease risk groups) were observed for the hypertension SMQ, as shown in Table 1.6 One patient treated with placebo discontinued due to a TEAE of hypertension.6,7     

Table 1. CV TEAE Hypertension - Phase 3, Double-Blind, Placebo-Controlled Migraine Prevention Trials5,6

Hypertension SMQ

Treatment Group

All Patients
n/N (%)

CV Disease Risk Group - YES
n/N (%)

CV Disease Risk Group - NO
n/N (%)

Patients with ≥1 narrow scope PT

PBO

18/1451 (1.2)

6/269 (2.2)

12/1182 (1.0)

GMB 120 mg

9/705 (1.3)

2/123 (1.6)

7/582 (1.2)

GMB 240 mg

7/730 (1.0)

3/124 (2.4)

4/606 (0.7)

GMB Pooled

16/1435 (1.1)

5/247 (2.0)

11/1188 (0.9)

Abbreviations: CV = cardiovascular; GMB = galcanezumab; GMB pooled = GMB 120 mg and GMB 240 mg pooled; MedDRA = Medical Dictionary for Regulatory Activities; PBO = placebo; PT = preferred term; SMQ = standardized MedDRA query; TEAE = treatment-emergent adverse event.

Changes in Use of CV Concomitant Medications by CV Disease Risk Group

A similar proportion of galcanezumab- and placebo-treated patients in the CV disease risk “yes” subgroup had an increased dose of or started new antihypertensive medications. More patients in the CV disease risk "yes" group increased dose of or started new antihypertensive medications as shown in Table 2.6

Table 2. Dose Increase or New Start of Concomitant Antihypertensive Medications - Phase 3, Double-Blind, Placebo-Controlled Migraine Prevention Trials5,6

Medication Group

All Patients PBO (%)

All Patients
GMB Pooled (%)

CV Disease Risk "Yes" Group PBO (%)

CV Disease Risk "Yes" Group GMB Pooled (%)

CV Disease Risk "No" Group PBO (%)

CV Disease Risk "No" Group GMB Pooled (%)

Antihypertensives

2.3

1.6

7.8

4.1

1.1

1.1

Abbreviations: CV = cardiovascular; GMB = galcanezumab; GMB Pooled = GMB 120 mg and GMB 240 mg pooled; PBO = placebo.

Categorical Increases in Blood Pressure and Pulse in Patients With Elevated Baseline Values

Among patients with elevated blood pressure (systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg) or elevated pulse rate (>100 beats per minute) at baseline, the percentages that experienced a categorical increase in systolic blood pressure, diastolic blood pressure, or pulse rate from baseline were not significantly different between the placebo and galcanezumab treatment groups: Table 3.6

Table 3. Categorical Increases in Blood Pressurea and Pulseb in Patients With Elevated SBP, DBP, or Pulsec at Baseline: Phase 3, Double-Blind, Placebo-Controlled Migraine Prevention Trials6

Vital Signs

PBO
n/N (%)

GMB 120 mg
n/N (%)

GMB 240 mg
n/N (%)

SBP

2/78 (2.6)

2/33 (6.1)

0/35 (0)

DBP

16/118 (13.6)

3/52 (5.8)

8/57 (14.0)

Pulse

1/12 (8.3)

0/3 (0.0)

0/4 (0.0)

Abbreviations: bpm = beats per minute; DBP = diastolic blood pressure; GMB = galcanezumab; PBO = placebo; SBP = systolic blood pressure.

a A categorical increase (high) postbaseline was defined as ≥140 mmHg for SBP or ≥90 mmHg for DBP at any time postbaseline with a concomitant increase ≥20 mmHg (SBP) or ≥10 mmHg (DBP) from the baseline value.

b Defined as >100 bpm at any time postbaseline with a concomitant increase ≥15 bpm from baseline.

c Defined as SBP ≥140 mm Hg, DBP ≥90 mm Hg, or pulse >100 bpm at baseline.

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. 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

3. 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

4. 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

5. Data on file, Eli Lilly and Company and/or one of its subsidiaries.

6. Oakes 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

7. Bangs ME, Kudrow D, Wang S, et al. Safety and tolerability of monthly galcanezumab injections in patients with migraine: integrated results from migraine clinical studies. BMC Neurol. 2020;20(1):90. http://dx.doi.org/10.1186/s12883-020-01675-7

Glossary

CV = cardiovascular

MedDRA = Medical Dictionary for Regulatory Activities

PT = preferred term

SMQ = standard MedDRA query

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.

Date of Last Review: October 02, 2020


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