Emgality ® (galkanezumab)

För fullständig produktresumé för Emgality® se FASS.

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Emgality® ▼ (galcanezumab): Ändringar i biomarkörer vid migrän

Det finns för närvarande inga kommersiellt accepterade biomarkörer för att diagnostisera migrän eller övervaka behandlingseffektivitet.

CGRP Plasma Levels in the Phase 3 Migraine Prevention Clinical Trials

Although CGRP levels were measured during the galcanezumab phase 3 migraine prevention trials, there are currently no

  • accepted biomarkers for chronic or episodic migraine

  • commercial assays available to detect CGRP levels, or

  • recommendations in the galcanezumab prescribing information to measure CGRP levels at baseline or during treatment with galcanezumab .1-3

In the phase 3 placebo-controlled, double-blind migraine prevention studies,4-6 total CGRP concentrations increased after galcanezumab administration in patients with episodic or chronic migraine compared to placebo. This indicated that the antibody was

  • binding to CGRP, and

  • slowing the clearance of the CGRP that was bound to the antibody,Table 1.1,7

Higher total CGRP concentrations were associated with a greater change from baseline in reduction of monthly MHDs for patients with episodic or chronic migraine compared to patients that received placebo.1

CGRP Plasma Concentration

Galcanezumab is a humanised IgG4 monoclonal antibody that binds calcitonin gene-related peptide (CGRP) thus preventing its biological activity. Elevated blood concentrations of CGRP have been associated with migraine attacks. Galcanezumab binds to CGRP with high affinity (KD = 31 pM) and high specificity (> 10,000-fold vs related peptides adrenomedullin, amylin, calcitonin and intermedin).8

A drug-tolerant CGRP assay was used in the clinical program for migraine prevention to measure total CGRP concentrations (total CGRP = galcanezumab-bound CGRP + free CGRP).1,9

When galcanezumab is administered, the premise is that

  • CGRP will bind to galcanezumab, and

  • the amount of free CGRP that is available to interact with the CGRP receptors will be reduced.1,9

Upon galcanezumab administration, galcanezumab-bound CGRP is expected to take on the disposition characteristics of galcanezumab resulting in

  • a lower clearance than free CGRP, and

  • an increase in total CGRP concentration.1,9

Table 1. Total CGRP Plasma Mean Concentrations (ng/mL) at End of Double-Blind Treatment in the Phase 3 Migraine Prevention Studies1

 

PBO

GMB 120 mg

GMB 240 mg

EVOLVE-1a

0.89

4.25

5.13

EVOLVE-2a

0.54

3.93

4.98

REGAINb

0.53

4.02

4.85

Abbreviations: CGRP = calcitonin gene-related peptide; GMB = galcanezumab; PBO = placebo.

a Represents total CGRP plasma concentrations at month 6.

b Represents total CGRP plasma concentrations at month 3.

Note: Galcanezumab is indicated for the prophylaxis of migraine in adults who have at least 4 migraine days per month. The recommended dose is 120 mg galcanezumab injected subcutaneously once monthly, with a 240 mg loading dose as the initial dose .8 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.

References

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

2. Durham P, Papapetropoulos S. Biomarkers associated with migraine and their potential role in migraine management. Headache. 2013;53(8):1262-77. http://dx.doi.org/10.1111/head.12174.

3. Emgality [package insert]. Indianapolis, IN: Eli Lilly and Company; 2019.

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. Kielbasa W. Assessment of pharmacokinetics, target engagement and immunogenicity in patients with migraine administered galcanezumab, and anti-CGRP antibody. Poster presented at: 60th Annual Meeting of the American Headache Society (AHS): June 28 - July 1, 2018; San Francisco, CA.

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

9. Kielbasa W, Helton DL. A new era for migraine: Pharmacokinetic and pharmacodynamic insights into monoclonal antibodies with a focus on galcanezumab, an anti-CGRP antibody. Cephalalgia. 2019;39(10):1284-1297. http://dx.doi.org/10.1177/0333102419840780

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 2020 M01 09


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