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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).
Were hypersensitivity events / allergic reactions reported in patients treated with Emgality® (galcanezumab)?
Serious hypersensitivity reactions, including anaphylaxis, angioedema and urticaria, have been reported. The reactions may occur within 1 day or with a delayed onset ranging from more than 1 day to 4 weeks after administration.
Content overview
Hypersensitivity events from Emgality summary of product characteristics
Galcanezumab is contraindicated in patients with hypersensitivity to the active substance or to any of the excipients.1
Serious hypersensitivity
Serious hypersensitivity reactions including cases of anaphylaxis, angioedema and urticaria have been reported. 1
Serious hypersensitivity reactions may occur within 1 day after galcanezumab administration, however cases with a delayed onset (ranging from more than 1 day to 4 weeks after administration) have also been reported. In some cases, hypersensitivity reactions had a prolonged duration.1
If a serious hypersensitivity reaction occurs, administration of galcanezumab should be discontinued immediately and appropriate therapy initiated. Patients should be informed on the possibility of a delayed onset hypersensitivity reaction and instructed to contact their physician.1
Relevant adverse reactions listed in the SmPC
The system organ class "Immune system disorders" lists anaphylaxis and angioedema that have been reported in clinical studies and post-marketing reports (Frequency estimand rare, ≥ 1/10,000 to < 1/1,000).1
Furthermore both, pruritus and rash, are a common adverse reaction of galcanezumab (frequency estimand common, ≥ 1/100 to < 1/10) . Pruritus was reported by 0.7 % and 1.2 % of patients with 120 mg and 240 mg galcanezumab in migraine clinical trials, respectively.1
Urticaria has been reported by 0.3 % and 0.1 % of patients with 120 mg and 240 mg galcanezumab in migraine clinical trials. While urticaria is uncommon, serious cases have been reported in galcanezumab clinical studies.1
Read the full Summary of Product Characteristics for Emgality for full prescribing information and further details about adverse drug reactions reported in galcanezumab clinical trials and post-marketing reports.
Hypersensitivity events in the phase 3 migraine prevention studies
Galcanezumab has been studied in migraine prevention studies.2-6 A brief overview of the phase 3 migraine prevention is provided in the Summary of Study Design in the Migraine Prevention Studies. Hypersensitivity events from the migraine prevention studies are summarized separately below.
Characterization of hypersensitivity events
Most events
The time course of hypersensitivity events did not appear different in the galcanezumab-treated patients compared to placebo and there was no trend for an increase in hypersensitivity events with increasing treatment duration up to 12 months.7
Incidence of hypersensitivity events in the phase 3 migraine prevention studies
Likely hypersensitivity events in EVOLVE-1, EVOLVE-2, and REGAIN studies
Hypersensitivity events occurred more frequently in patients treated with galcanezumab than with placebo in
- EVOLVE-1
- EVOLVE-2, and
- REGAIN (Overview of Likely Hypersensitivity Events After Medical Review: Phase 3, Double-Blind, Placebo-Controlled Migraine Prevention Studies (EVOLVE-1, EVOLVE-2, and REGAIN)).8
When considering all galcanezumab-treated patients during all treatment phases, the frequency of hypersensitivity events was comparable to the frequencies observed during the double-blind treatment phase.7
Preferred Terma |
PBO
N=1451 n (%) |
GMB 120 mg
N=705 n (%) |
GMB 240 mg
N=730 n (%) |
Immediate (on day of drug administration) |
|||
Dermatitis contact |
1 (0.07) |
0 (0.00) |
0 (0.00) |
Injection site hypersensitivity |
0 (0.00) |
1 (0.14) |
1 (0.14) |
Injection site rash |
2 (0.14) |
3 (0.43) |
3 (0.41) |
Injection site urticaria |
1 (0.07) |
1 (0.14) |
1 (0.14) |
Pruritus allergic |
0 (0.00) |
1 (0.14) |
0 (0.00) |
Rash |
1 (0.07) |
0 (0.00) |
1 (0.14) |
Urticaria |
0 (0.00) |
0 (0.00) |
|
Nonimmediate (beyond day of drug administration) |
|||
Bronchospasm |
1 (0.07) |
0 (0.00) |
0 (0.00) |
Conjunctivitis allergic |
1 (0.07) |
0 (0.00) |
0 (0.00) |
Dermatitis allergic |
0 (0.00) |
3 (0.43)b |
0 (0.00) |
Dermatitis atopic |
1 (0.07) |
0 (0.00) |
1 (0.14) |
Dermatitis contact |
3 (0.21) |
3 (0.43) |
4 (0.55) |
Drug hypersensitivity |
1 (0.07) |
0 (0.00) |
0 (0.00) |
Eczema |
3 (0.21) |
1 (0.14) |
2 (0.27) |
Eye allergy |
0 (0.00) |
1 (0.14) |
0 (0.00) |
Hypersensitivity |
0 (0.00) |
3 (0.43)b |
2 (0.27)b |
Injection site hypersensitivity |
0 (0.00) |
0 (0.00) |
2 (0.27)b |
Injection site rash |
0 (0.00) |
4 (0.57)b |
2 (0.27)b |
Rash |
14 (0.96) |
5 (0.71) |
6 (0.82) |
Rash erythematous |
1 (0.07) |
0 (0.00) |
1 (0.14) |
Rash generalized |
1 (0.07) |
1 (0.14) |
1 (0.14) |
Rash maculopapular |
1 (0.07) |
1 (0.14) |
0 (0.00) |
Rash papulosquamous |
0 (0.00) |
1 (0.14) |
1 (0.14) |
Rash pruritic |
0 (0.00) |
2 (0.28)b |
1 (0.14) |
Rhinitis allergic |
3 (0.21) |
3 (0.43) |
4 (0.55) |
Urticaria |
5 (0.34) |
1 (0.14) |
1 (0.14) |
Abbreviations: GMB = galcanezumab; MedDRA = Medical Dictionary for Regulatory Activities; PBO = placebo.
aIdentified by a standardized MedDRA query (version 19.1) narrow term search.
bp≤.05 vs PBO.
cCases reported as nonserious urticaria.
Incidence of likely hypersensitivity events in the CONQUER study
The frequency of treatment-emergent likely hypersensitivity events was not significantly different between the galcanezumab and placebo treatment groups during double-blind treatment in the CONQUER study: Overview of Likely Hypersensitivity Events After Medical Review: Double-Blind Treatment Phase of the CONQUER Study.5
Preferred Terma |
PBO |
GMB 120 mg |
Within 24 hours |
||
Rash |
1 (0.43) |
0 (0.00) |
Urticaria |
1 (0.43) |
0 (0.00) |
After 24 hours |
||
Eczema |
1 (0.43) |
0 (0.00) |
Injection site hypersensitivity |
0 (0.00) |
1 (0.43) |
Rash |
2 (0.87) |
3 (1.29) |
Rash generalized |
0 (0.00) |
1 (0.43) |
Rash macular |
1 (0.43) |
0 (0.00) |
Rhinitis allergic |
2 (0.87) |
1 (0.43) |
Toxic skin eruption |
0 (0.00) |
1 (0.43) |
Abbreviations: GMB = galcanezumab; MedDRA = Medical Dictionary for Regulatory Activities; PBO = placebo.
aIdentified by a standardized MedDRA query (version 22.0) narrow term search.
Incidence of likely hypersensitivity events in the open-label safety study
The incidence of treatment-emergent adverse events related to hypersensitivity events was similar between galcanezumab dose groups during open-label treatment in the 12-month open-label safety study: Overview of Likely Hypersensitivity Events After Medical Review: Open-Label Safety Study.7
Preferred Termb |
GMB 120 mg |
GMB 240 mg |
Dermatitis allergic |
2 (1.55) |
0 (0.00) |
Hypersensitivity |
1 (0.78) |
0 (0.00) |
Injection site rash |
1 (0.78) |
1 (0.71) |
Injection site urticaria |
1 (0.78) |
0 (0.00) |
Pruritus allergic |
0 (0.00) |
1 (0.71) |
Rash |
1 (0.78) |
1 (0.71) |
Rash generalized |
0 (0.00) |
1 (0.71) |
Rash maculo-papular |
0 (0.00) |
1 (0.71) |
Rhinitis allergic |
1 (0.78) |
1 (0.71) |
Skin reaction |
0 (0.00) |
1 (0.71) |
Urticaria |
1 (0.78) |
1 (0.71) |
Abbreviations: GMB = galcanezumab; MedDRA = Medical Dictionary for Regulatory Activities.
aOf the 10 treatment-emergent hypersensitivity events where reaction timing was available, events that occurred on the day of injection included rash (n=2), injection site urticaria (n=1), and pruritus (n=1). All other events occurred after the day of injection.
bIdentified by a standardized MedDRA query (version 19.1) narrow term search.
Serious adverse events
No patient in any treatment group had an immediate or a nonimmediate hypersensitivity-related serious adverse event (SAE) during the double-blind treatment period in the EVOLVE-1, EVOLVE-2, REGAIN, and CONQUER studies.5,7
Two serious cases of urticaria occurred during the open-label and posttreatment phase of REGAIN. Neither patient
- reported other associated symptoms, or
- was positive for treatment-emergent antidrug antibodies.8
Hypersensitivity related treatment-emergent adverse events leading to study discontinuations
In the EVOLVE-1, EVOLVE-2, and REGAIN studies, no event leading to discontinuation was reported by >1 patient, and all events resolved with supportive care. Patients discontinued because of:
- generalized rash and pruritic rash in the galcanezumab 120-mg group, and
- dyspnea and hypersensitivity in the galcanezumab 240-mg group.8
Discontinuations due to a hypersensitivity event during CONQUER were reported by
One patient discontinued due to a hypersensitivity event of rash in the open-label safety study.6
Postmarketing spontaneous reports related to angioedema, anaphylactic reaction and rash
Based on postmarketing spontaneous reports from the Eli Lilly and Company spontaneous adverse event (AE) database received through September 27, 2022,
- angioedema and anaphylactic reaction were very rarely reported (<0.01%), and
- rash was rarely reported (≥0.01% and <0.1%).7
Through September 27, 2022, there were reported postmarketing cases consistent with hypersensitivity in the Eli Lilly and Company spontaneous AE database. There have been no fatal cases of serious hypersensitivity.7
Postmarketing cases consistent with anaphylaxis, angioedema, and rash through March 27, 2019 are summarized in Galcanezumab Postmarketing Cases Consistent With Anaphylaxis, Angioedema, and Rash (Through March 27, 2019). This specific information is not available from the reporting period through September 27, 2022.
|
Timing |
Details |
Anaphylaxis |
The timing of the event was immediatea in a majority of cases. |
In a majority of cases, patients went to the emergency room or urgent care, or were hospitalized. |
Angioedema |
The timing of the event was nonimmediate,b in a majority of cases.
|
The majority of cases were nonserious and several cases were serious (throat swelling and facial swelling). |
Rash |
The information on timing was not reported or undetermined in a majority of cases.
|
All rashes were reported as nonserious.
|
aImmediate = occurring within 24 hours of galcanezumab administration.
bNonimmediate = occurring greater than 24 hours after galcanezumab administration.
Postmarketing data do not necessarily represent the rate of occurrence of an AE in a treated population, but they represent a reporting rate of a particular AE to the company. Spontaneous reporting of AEs 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.9
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.9
References
1Emgality [summary of product characteristics]. Eli Lilly Nederland B.V., The Netherlands.
2Stauffer 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
3Skljarevski 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
4Detke 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
5Mulleners WM, Kim BK, Láinez MJA, et al. Safety and efficacy of galcanezumab in patients for whom previous migraine preventive medication from two to four categories had failed (CONQUER): a multicentre, randomised, double-blind, placebo-controlled, phase 3b trial. Lancet Neurol. 2020;19(10):814-825. http://dx.doi.org/10.1016/S1474-4422(20)30279-9
6Camporeale A, Kudrow D, Sides R, et al. A phase 3, long-term, open-label safety study of galcanezumab in patients with migraine. BMC Neurol. 2018;18(1):188. http://dx.doi.org/10.1186/s12883-018-1193-2
7Data on file, Eli Lilly and Company and/or one of its subsidiaries.
8Bangs 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):25. https://doi.org/10.1186/s12883-020-1609-7
9Goldman 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
10Levin M, Silberstein SD, Gilbert R, et al. Basic considerations for the use of monoclonal antibodies in migraine. Headache. 2018;58(10):1689-1696. http://dx.doi.org/10.1111/head.13439
Appendix
Background information
Therapeutic proteins, including monoclonal antibodies, have been associated with hypersensitivity events.10 Therefore, these events were closely monitored in the phase 3 studies, in order to understand the potential for hypersensitivity with the use of galcanezumab.7
Galcanezumab is a self-administered medication. The package labeling contains no requirements to monitor the patient after administration for hypersensitivity reactions.7
It is not known if previous hypersensitivity to another biological product constitutes a risk factor for treatment with galcanezumab since galcanezumab studies excluded patients with a history of hypersensitivity to
- monoclonal antibodies, or
- therapeutic proteins.7
Hypersensitivity is neither predictable nor preventable. No correlation with antibody formation has been observed.7
Overview of Phase 3 double-blind, placebo-controlled migraine prevention studies
Galcanezumab has been studied in phase 3 randomized, double-blind, placebo-controlled studies in adult patients for the prevention of
Galcanezumab has also been studied in a phase 3, open-label, 12-month safety study for the prevention of episodic or chronic migraine.6
The galcanezumab doses used and duration of the migraine prevention studies are summarized in Summary of Study Design in the Migraine Prevention Studies.
Study Name |
Treatments |
Study Duration |
EVOLVE-12 EVOLVE-23 |
PBO, GMB 120 mg monthly,b |
6-month double-blind |
REGAIN4 |
PBO, GMB 120 mg monthly,b |
3-month double-blind, |
CONQUER5 |
PBO or GMB 120 mg SQ monthlyb |
3-month double-blind, |
CGAJ6 |
GMB 120 mgb |
12-month open-label |
Abbreviations: GMB = galcanezumab; PBO = placebo; SQ = subcutaneous.
aWith the exception of study CGAJ, all studies were randomized, double-blind, and placebo-controlled.
bThe initial dose was administered as a 240-mg loading dose, followed by subsequent monthly doses of 120 mg.
▼ 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: 13 January 2023