Emgality ® (galkanezumab)

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Emgality® ▼ (galcanezumab): Överkänslighetsreaktioner vid migränförebyggande

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

Further Information from Summary of Product Characteristics

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

Serious hypersensitivity reactions including cases of anaphylaxis, angioedema and urticaria have been reported. If a serious hypersensitivity reaction occurs, administration of galcanezumab should be discontinued immediately and appropriate therapy initiated.1

Based on post-marketing reports

  • anaphylaxis and angioedema were both rarely reported adverse reactions to galcanezumab (≥0.01% - (0.1%),

  • rash was a common adverse reaction to galcanezumab (≥1% - <10%) .1 

Injection site pain or reactions

Injection site pain and Injection site reactions are very common adverse reactions of galcanezumab.

  • Injection site pain was reported by 10.1 % and 11.6 % of patients with 120 mg and 240 mg galcanezumab, respectively.

  • Injection site reactions were reported by 9.9 % and 14.5 % of patients  with 120 mg and 240 mg galcanezumab, respectively.1

With regard to Injection site reactions, the most frequently reported terms (≥ 1 %) were:

  • Injection site reaction

  • Injection site erythema

  • Injection site pruritus

  • Injection site bruising

  • Injection site swelling.1

The majority of events related to the injection site 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

The majority of injection site reactions were reported within 1 day and on average resolved within 5 days.1

In 86 % of the patients reporting injection site pain, the event occurred within 1 hour of injection and resolved on average in 1 day. One percent of the patients exposed to galcanezumab during the phase 3 studies experienced severe pain at the injection site.1

Pruritus

Pruritus is a common adverse reaction of galcanezumab. Pruritus 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. Urticaria was reported by 0.3 % and 0.1 % of patients with 120 mg and 240 mg galcanezumab, respectively.1

While urticaria is uncommon, serious cases of urticaria have been reported in galcanezumab clinical studies.1

Summary of Hypersensitivity Events

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

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. Serious hypersensitivity reactions could occur days after administration and may be prolonged.3

Galcanezumab has been studied in migraine prevention.4-6A brief overview of the phase 3 double-blind, placebo-controlled studies is provided in theAppendix. Hypersensitivity events from the double-blind treatment phase for each population are summarized separately below. 

Additionally, postmarketing reports of hypersensitivity are summarized separately in the Postmarketing Spontaneous Reports section.

Hypersensitivity Events in the Phase 3 Migraine Prevention Studies

Summary of Hypersensitivity Events in Migraine Prevention Studies

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.

Hypersensitivity events occurred more frequently in patients treated with galcanezumab than with placebo (Table 1).7 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.3

Most events

  • were non-serious

  • were mild or moderate in severity, and

  • did not lead to discontinuation of galcanezumab.3,7 

There were no anaphylaxis events reported in the migraine prevention studies.7

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.3

Table 1. Overview of Likely Hypersensitivity Events After Medical Review: Phase 3 Double-Blind, Placebo-Controlled Migraine Prevention Studies3

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)

Non-Immediate (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.

a Identified by a standardized MedDRA query (version 19.1) narrow term search.

b p≤.05 vs placebo.

c Cases reported as non-serious urticaria.

Serious Adverse Events in Migraine Prevention Studies

No patient in any treatment group had an immediate nor a non-immediate hypersensitivity related SAE during the double-blind treatment period in the phase 3 migraine prevention studies.3

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 anti-drug-antibodies.7 

Discontinuations Due to Hypersensitivity Adverse Events in Migraine Prevention Studies

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

  • 2 each with galcanezumab 120-mg and 240-mg dose groups, and

  • 1 patient in placebo.3

The events resulting in treatment discontinuation in galcanezumab-treated patients were

  • generalized rash and pruritic rash in the galcanezumab 120 mg group, and

  • dyspnea and hypersensitivity in the galcanezumab 240 mg group.3

No event leading to discontinuation was reported by >1 patient, and all events resolved. Supportive care was implemented for all events.3

Postmarketing Spontaneous Reports

Based on postmarketing spontaneous reports

  • anaphylaxis and angioedema were both rarely reported (≥0.01% to <0.1%), and

  • rash was commonly reported (≥1% to <10%).3

Through 27 March 2019, there were reported postmarketing cases consistent with hypersensitivity in the Eli Lilly and Company spontaneous AE database. None of these cases reported a fatal outcome.3

Postmarketing cases consistent with anaphylaxis, angioedema, and rash through 27 March 2019 are provided in Table 2.

Table 2. Galcanezumab Postmarketing Cases Consistent With Anaphylaxis, Angioedema, and Rash (Through 27 March 2019)3

 

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 non-immediate,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.

a Immediate = occurring within 24 hours of galcanezumab administration.

b Non-immediate = 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.8

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.8

References

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

2. Levin 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

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

4. 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

5. 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

6. 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

7. Bangs ME, Kudrow D, Wang S, et al. Safety and tolerability of monthly galcanezumab injections in patients with migraine: integrated results from migraine studies. BMC Neurology. 2020;20(1):25. http://dx.doi.org/10.1186/s12883-020-1609-7. Published correction appears in BMC Neurology. 2020;20(1):90. http://dx.doi.org/10.1186/s12883-020-01675-7

8. Goldman SA. Limitations and strengths of spontaneous reports data. Clin Ther. 1998;20(suppl 3):C40-44. http://dx.doi.org/10.1016/S0149-2918(98)80007-6

Glossary

AE = adverse event

SAE = serious adverse event

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.

Appendix

Overview of Phase 3 Migraine 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),4,5 and

  • chronic migraine (REGAIN).6

The studies had a duration of

  • 6 months for prevention of episodic migraine,4,5 and

  • 3 months for prevention of chronic migraine, with an optional 9-month open-label extension phase.6 

Patients were randomized at the beginning of double-blind treatment in a 2:1:1 ratio to receive monthly subcutaneous injections of 

  • placebo

  • galcanezumab 120 mg with a loading dose of 240 mg, or

  • galcanezumab 240 mg.4-6 

Datum fӧr senaste ӧversyn 2020 M01 09


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