Emgality ® (galkanezumab)

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Har allergiska reaktioner observerats med Emgality® ▼ (galcanezumab)?

Allvarliga överkänslighetsreaktioner, inklusive fall av anafylax, angioödem och urticaria, har rapporterats. Om en allvarlig överkänslighetsreaktion inträffar, avbryt omedelbart galcanezumab och initiera lämplig behandling.

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Most Common Hypersensitivity Events from Emgality Label

Injection site reactions

Injection site reaction is a very common adverse reaction of galcanezumab. It was reported by 9.9 % and 14.5 % of patients with 120 mg and 240 mg galcanezumab, respectively.

The most frequently reported injection site reactions were:

  • injection site reaction
  • injection site erythema
  • injection site pruritus
  • injection site bruising, and
  • injection site swelling.1

Most of them were mild to moderate and less than 0.5 % of patients exposed to galcanezumab during the phase 3 studies discontinued the treatment due to an injection site reaction.1

Most injection site reactions were reported within 1 day and on average resolved within 5 days.1

Pruritus

Pruritus is a common adverse reaction of galcanezumab. It was reported by 0.7 % and 1.2 % of patients with 120 mg and 240 mg galcanezumab, respectively.1

Urticaria

Urticaria is an uncommon adverse reaction of galcanezumab reported in galcanezumab clinical trials. Urticaria was reported by 0.3 % and 0.1 % of patients with 120 mg and 240 mg galcanezumab, respectively. Some cases were reported as serious.1

Hypersensitivity events in the phase 3 migraine preventive studies

Characterization of Hypersensitivity Events

Most events

  • were non-serious
  • were mild or moderate in severity, and
  • did not lead to discontinuation of galcanezumab.2,3 

The time course of hypersensitivity events was similar between galcanezumab and placebo and there was no trend for an increase in hypersensitivity events with increasing treatment duration up to 12 months.2

Incidence of Hypersensitivity Events

There were no anaphylaxis events reported in the phase 3 migraine prevention studies.2,3

In EVOLVE-1, EVOLVE-2, and REGAIN, hypersensitivity events occurred more frequently in patients treated with galcanezumab than with placebo (Overview of Likely Hypersensitivity Events After Medical Review: Phase 3 Double-Blind, Placebo-Controlled Migraine Prevention Studies (EVOLVE-1, EVOLVE-2, REGAIN)).3 The frequency of hypersensitivity events of galcanezumab-treated patients was comparable between all treatment phases.2

Overview of Likely Hypersensitivity Events After Medical Review: Phase 3 Double-Blind, Placebo-Controlled Migraine Prevention Studies (EVOLVE-1, EVOLVE-2, REGAIN)2

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)

2 (0.28)bc

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 placebo.

cCases reported as nonserious urticaria.

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 and during open-label treatment in the 12-month open-label safety studies and during open-label treatment in the 12-month open-label safety studies: Overview of Likely Hypersensitivity Events After Medical Review: Double-Blind Treatment Phase of the CONQUER Study and Overview of Likely Hypersensitivity Events After Medical Review: Open-Label Safety Study.2,4 

Overview of Likely Hypersensitivity Events After Medical Review: Double-Blind Treatment Phase of the CONQUER Study2,4

Preferred Terma

PBO
N=230
n (%)

GMB 120 mg
N=232
n (%)

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.

Overview of Likely Hypersensitivity Events After Medical Review:a Open-Label Safety Study2

Preferred Termb

GMB 120 mg
N=129
n (%)

GMB 240 mg
N=141
n (%)

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.

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.

Serious Adverse Events

In the double-blind treatment period of the EVOLVE-1, EVOLVE-2, REGAIN, and CONQUER studies there was no hypersensitivity-related serious adverse events (SAE) reported.2,4

In the open-label and posttreatment phase of REGAIN, two serious cases of urticaria were reported. Neither patient

  • reported other associated symptoms, or
  • was positive for treatment-emergent anti-drug-antibodies.3 

Hypersensitivity Related Treatment-Emergent Adverse Events Leading to Study Discontinuations

There were 5 patients who discontinued due to a likely hypersensitivity event:

  • 2 patients receiving 120 mg galcanezumab
  • 2 patients receiving 240 mg galcanezumab, and
  • 1 patient in placebo.2

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.3

Discontinuations due to a hypersensitivity event during CONQUER were reported by

  • 1 galcanezumab-treated patient during double-blind treatment (rash generalized),4 and
  • 1 galcanezumab-treated patient during open-label treatment (upper body rash).2

One patient discontinued due to a hypersensitivity event of rash in the open-label safety study.5

Postmarketing Spontaneous Reports

Based on postmarketing spontaneous reports through March 27, 2021

  • angioedema was very rarely reported (<0.01%)
  • anaphylactic reaction was very rarely reported (<0.01%), and
  • rash was rarely reported (≥0.01% and <0.1%).2

Through March 27, 2021, there were reported postmarketing cases consistent with hypersensitivity in the Eli Lilly and Company spontaneous adverse event (AE) database. There have been no fatal cases of serious hypersensitivity.2

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 March 27, 2021.

Galcanezumab Postmarketing Cases Consistent With Anaphylaxis, Angioedema, and Rash (Through March 27, 2019)2

 

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.

 

In several cases, the patient had a history of allergies.

Angioedema

The timing of the event was nonimmediate,b in a majority of cases.


In several cases, the time to onset was unknown.

The majority of cases were nonserious and several cases were serious (throat swelling and facial swelling).

 

Some cases were confounded by underlying inflammatory/infectious conditions or a possible insect bite.

Rash

The information on timing was not reported or undetermined in a majority of cases.


In some cases, the rash was reported to occur on the same day of either the initial or loading dose (minutes or hours after injections) or during the following days.


In a few other cases, the rash occurred at the time of the subsequent monthly doses.

All rashes were reported as nonserious.


Most events were reported simply as rash, but generalized, pruritic, erythematous, macular, vesicular, and papular rashes were also reported in a few cases.

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.6

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.6

References

1Emgality [summary of product characteristics]. Eli Lilly Nederland B.V., The Netherlands.

2Data on file, Eli Lilly and Company and/or one of its subsidiaries.

3Bangs 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

4Mulleners 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

5Camporeale 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

6Goldman 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

7Levin 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

8Stauffer 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

9Skljarevski 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

10Detke 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

Appendix

Background information

Therapeutic proteins, including monoclonal antibodies, have been associated with hypersensitivity events.7 Therefore, these events were closely monitored in the phase 3 studies, in order to understand the potential for hypersensitivity with the use of galcanezumab.2 

Galcanezumab is a self-administered medication. The package labeling contains no requirements to monitor the patient after administration for hypersensitivity reactions.2

Galcanezumab is contraindicated in patients with hypersensitivity to the active substance or to any of the excipients (L-histidine, L-histidine hydrochloride monohydrate, Polysorbate 80, Sodium chloride, Water for injections).1

Patients with a history of hypersensitivity to monoclonal antibodies or therapeutic proteins were excluded from the clinical development program, therefore it is not known if previous hypersensitivity to another biological product constitutes a risk factor for treatment with galcanezumab.2 Hypersensitivity is neither predictable nor preventable. No correlation with antibody formation has been observed.

Serious hypersensitivity reactions, including cases of anaphylaxis, angioedema, and urticaria, have been reported with galcanezumab. If a serious hypersensitivity reaction occurs, discontinue galcanezumab immediately and initiate appropriate therapy.1

Serious hypersensitivity reactions may occur within 1 day after galcanezumab administration, however cases with a delayed onset have also been reported.1

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

  • episodic migraine (EVOLVE-1 and EVOLVE-2)8,9
  • chronic migraine (REGAIN),10 and
  • episodic or chronic migraine that has not benefited from 2 to 4 previous migraine prevention medication categories (CONQUER).4

Galcanezumab has also been studied in a phase 3, open-label, 12-month safety study for the prevention of episodic or chronic migraine.5

The galcanezumab doses used and duration of the migraine prevention studies are summarized in Summary of Study Design in the Migraine Prevention Studies.

Summary of Study Design in the Migraine Prevention Studiesa

 

GMB Doses Studied

Study Duration

EVOLVE studies8,9

120 mg monthlyb
or
240 mg monthly

6-month double-blind

REGAIN10

120 mg monthlyb
or
240 mg monthly

3-month double-blind,
with optional 9-month open-label extension

CONQUER4

120 mg monthlyb

3-month double-blind, 
with optional 3-month open-label extension

CGAJ5

120 mg monthlyb
or
240 mg monthly

12-month open-label

Abbreviation: GMB = galcanezumab.

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.

Datum fӧr senaste ӧversyn July 30, 2021


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