Emgality ® (galkanezumab)

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Emgality® ▼ (galcanezumab): Yrsel i kliniska prövningar

Yrsel förekom hos 1% av patienterna i galcanezumab-armarna jämfört med 0,2% i placebo-armen. De flesta händelser var milda eller måttliga i svårighetsgrad och försvann under ≤7 dagar.

Vertigo General Information

Dizziness is a non-specific term that is also sometimes used to describe vertigo.1 The 4 recognized types of dizziness are

  • vertigo

  • disequilibrium

  • presyncope, or

  • lightheadedness.

Vertigo refers to the illusion of environmental motion (typically with a rotational component) or a disorientation in space.1 Vertigo reflects some level of dysfunction of the vestibular system. It is classically described as

  • spinning

  • whirling

  • like getting off a merry-go-round, or

  • the ground tilts up and down, like being on a boat at sea.

Patients with migraine often have audiovestibular symptoms including vertigo, tinnitus, phonophobia, and hearing loss.2,3

Summary of Vertigo in the Phase 3 Migraine Prevention Studies

Overview of Phase 3 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),4,5 and

  • chronic migraine (REGAIN).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 

  • The recommended dose is 120 mg galcanezumab injected subcutaneously once monthly, with a 240 mg loading dose as the initial dose.7 Please note that the results of a maintenance dose of 240 mg galcanezumab once monthly are also described here. Even though this dose has been tested in pivotal studies, it has not been approved and therefore is not recommended.

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 

Incidence and Characterization of Vertigo Events

Vertigo is a common adverse reaction of galcanezumab. Vertigo was reported by 0.7 % and 1.2 % of patients with 120 mg and 240 mg galcanezumab, respectively.7

The incidence and severity of vertigo during the double-blind treatment phase of the galcanezumab studies for migraine prevention are summarized in Table 1.

The vertigo reports in galcanezumab-treated patients were mild or moderate in severity in the majority of reports.8

A total of 14 patients in the galcanezumab groups reported 17 events of vertigo.8 Of those, 12 patients reported a single event of vertigo each, with 6 of 12 events reported following the first dose. Of the 2 patients reporting multiple vertigo events

  • 1 patient reported 3 events of vertigo, each occurring after the first, second, and third doses, respectively, and

  • another patient reported 2 events of vertigo, each occurring the day after the first, and second doses, respectively. 

Both patients were from the 6-month episodic migraine prevention studies and completed the rest of their dosing visits without recurrence.8

The onset of vertigo in the 17 events in galcanezumab-treated patients was

  • within 7 days in 10 events, of which 6 were reported the day of or the day after a dose, and

  • between 8 and 32 days after a dose in the remaining 7 cases.8

No galcanezumab-treated patients discontinued due to vertigo.8 One placebo-treated patient discontinued due to severe vertigo 2 days after receiving the third dose.

Galcanezumab may have a minor influence on the ability to drive and use machines. Vertigo may occur following the administration of galcanezumab.7

Since vertigo may occur following the administration of galcanezumab, it may have a minor influence on the ability to drive and use machines.7

No galcanezumab-treated patients who reported vertigo reported a(n)

  • road traffic accident

  • accident at home, or 

  • fall.8

Table 1. Summary of Treatment-Emergent Vertigo Events: Migraine Prevention Double-Blind Treatment Phase8

 

PBO
N=1451
n (%)

GMB 120 mg
N=705
n (%)

GMB 240 mg
N=730
n (%)

Frequency

3 (0.2)

5 (0.7)

9 (1.2)

Severity

---

---

---

   Mild

0 (0.0)

2 (0.3)

7 (1.0)

   Moderate

2 (0.1)

1 (0.1)

2 (0.3)

   Severe

1 (0.1)

2 (0.3)

0 (0.0)

Abbreviations: GMB = galcanezumab; PBO = placebo.

Note: The recommended dose is 120 mg galcanezumab injected subcutaneously once monthly, with a 240 mg loading dose as the initial dose .7 The results of a maintenance dose of galcanezumab 240 mg once monthly are also described here. Even though this dose has been tested in pivotal studies, it has not been approved and therefore is not recommended.

Duration of Treatment-Emergent Vertigo Events

The duration of vertigo events by treatment group is summarized in Table 2.

Table 2. Durationa of Treatment-Emergent Vertigo Events: Double-Blind Treatment Phase8

TEAE duration

N

PBO
(n)

GMB 120 mg
(n)

GMB 240 mg
(n)

7 days

13

1

5

7

>7 to ≤30 days

1

0

0

1

>30 to ≤60 days

2

0

1b

1c

Not resolved

1

1d

0

0

Abbreviation: GMB = galcanezumab; PBO = placebo; TEAE = treatment-emergent adverse event.

a Duration for treatment-emergent vertigo events were calculated only for those events with a documented start and end date.

b Patient received all planned study doses. Event occurred on day of the first dose with a duration of 32 days; 5 additional monthly doses received with no recurrence.

c Patient received all planned study doses. Event occurred 8 days after the second dose with a duration of 35 days; 4 additional monthly doses received with no recurrence.

d Patient received all planned study doses. Event occurred 8 days after the fifth dose and was not resolved by the end of study follow-up.

Note: The recommended dose is 120 mg galcanezumab injected subcutaneously once monthly, with a 240 mg loading dose as the initial dose .7 The results of a maintenance dose of galcanezumab 240 mg once monthly are also described here. Even though this dose has been tested in pivotal studies, it has not been approved and therefore is not recommended.

Biological Plausibility

Vertigo has been identified by Eli Lilly and Company as an adverse drug reaction.8 An adverse drug reaction is a clinical event that is considered related to exposure to a drug. Adverse drug reaction determination is based on the review of

  • all the planned summaries or analyses

  • any additional ad-hoc displays, and

  • case reviews needed to assist Lilly Medical in such determination.

In addition to the data presented here, results of human ex-vivo studies in both cochlear and vestibular efferent systems provide evidence of the role of calcitonin gene-related peptide in the neurotransmission and neuroregulation of these systems, supporting the biological plausibility of an association between the inhibition of calcitonin gene-related peptide and interference with vestibular function.9,10

Therapeutic Indication

Galcanezumab is indicated for the prophylaxis of migraine in adults who have at least 4 migraine days per month.7

The recommended dose is 120 mg galcanezumab injected subcutaneously once monthly, with a 240 mg loading dose as the initial dose.7

References

1. Reilly BM. Dizziness. In: Walker HK, Hall WD, Hurst JW, editors. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition. Boston: Butterworths; 1990. Chapter 212. Available from: https://www.ncbi.nlm.nih.gov/books/NBK325/

2. Lempert T,Neuhauser H. Epidemiology of vertigo, migraine and vestibular migraine. J Neurol. 2009;256(3):333-338. http://dx.doi.org/10.1007/s00415-009-0149-2

3. Dash AK, Panda N, Khandelwal G, et al. Migraine and audiovestibular dysfunction: is there a correlation? Am J Otolaryngol. 2008;29(5):295-299. http://dx.doi.org/10.1016/j.amjoto.2007.09.004

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

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

9. Kong WJ, Scholtz AW, Kammen-Jolly K, et al. Ultrastructural evaluation of calcitonin gene-related peptide immunoreactivity in the human cochlea and vestibular endorgans. Eur J Neurosci. 2002;15(3):487-497. https://doi.org/10.1046/j.0953-816x.2001.01880.x

10. Schrott-Fischer A, Kammen-Jolly K, Scholtz A, et al. Efferent neurotransmitters in the human cochlea and vestibule. Acta Otolaryngol. 2007;127(1):13-19. http://dx.doi.org/10.1080/00016480600652123

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.

Datum fӧr senaste ӧversyn 2019 M02 14


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