Emgality ® (galkanezumab)

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Emgality® ▼ (galcanezumab): Effekt på CGRP-nivåer

De totala CGRP-nivåerna i serum ökade efter administrering av galcanezumab vilket indikerar att CGRP binder till galcanezumab och reducerar fri CGRP.

Detailed Information

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).1

CGRP Plasma Concentration

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).2,3

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.2,3

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.2,3

In the phase 3 double-blind, placebo-controlled migraine prevention studies,4-6 total CGRP concentrations increased after galcanezumab administration 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 as shown in Table 1 .2,3

Higher total CGRP concentrations in galcanezumab-treated patients were associated with a greater change from baseline compared to placebo in reduction of

  • monthly migraine headache days for patients with episodic or chronic migraine.3 

Table 1. Total CGRP Plasma Mean Concentrations (ng/mL) at End of Double-Blind Treatment in the Phase 3 Migraine Prevention Studies2

 

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

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

3. 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

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

Glossary

CGRP = calcitonin gene-related peptide

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 M02 06


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