Emgality ® ▼ (galcanezumab)

This information is intended for UK registered healthcare professionals only as a scientific exchange in response to your search for information.For current prescribing information for all Lilly products, including Summaries of Product Characteristics, Patient Information Leaflets and Instructions for Use, please visit: www.medicines.org.uk (England, Scotland, Wales) or www.emcmedicines.com/en-GB/northernireland/ (Northern Ireland).

Should Emgality® ▼ (galcanezumab) loading dose be repeated following missed doses or treatment interruption?

From a pharmacokinetic perspective, consider repeating a loading dose if 3 consecutive monthly doses are missed.

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How are missed or delayed galcanezumab doses managed?

Patients should be instructed to

  • inject a missed dose as soon as possible and then resume their monthly dosing
  • not to take a double dose to make up for forgotten injection, and
  • inject a forgotten dose of galcanezumab as soon as possible and then inject the next dose after a month from that date. 1,2

Dose Administration and Timing Parameters in 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)3,4
  • chronic migraine (REGAIN),5 and
  • episodic or chronic migraine that has not benefited from 2 to 4 previous migraine prevention medication categories (CONQUER).6

In the phase 3 clinical trials, injections were allowed to be administered within ±2 days of the scheduled visit.7

The recommended dose is 120 mg injected subcutaneously once monthly, with a 240-mg loading dose as the initial dose.1

Considerations for Repeating a Loading Dose After Missed Doses

The pharmacokinetic (PK) profile of galcanezumab enables some flexibility with regard to when doses are administered. Prolonged dosing delays will

  • decrease galcanezumab concentrations, and
  • potentially reduce efficacy.7

It may require some time to re-establish steady-state galcanezumab plasma concentrations when dosing is resumed. To determine whether a repeat loading dose is warranted, please consider the

  • elimination half-life (t1/2), and
  • other PK characteristics of galcanezumab.

In healthy subjects and patients with episodic or chronic migraine, galcanezumab has a

  • time of maximum observed drug concentration of 5 days, and
  • elimination half-life of 27 days.7,8

Steady-state concentrations are achieved by month 1 for the 120-mg monthly dose with a 240-mg loading dose.8

After missing 3 consecutive monthly doses, approximately 12% of the galcanezumab concentration relative to steady state will be remaining (Effect of Missed Monthly Doses on Galcanezumab Steady-State Concentrations).7

Therefore, after missing 3 consecutive monthly doses, repeating a loading dose should be considered from a PK perspective.

Clinicians should use their judgment to determine whether a repeat loading dose is needed.

Effect of Missed Monthly Doses on Galcanezumab Steady-State Concentrations7

Number of Consecutive
Missed Monthly Doses

Time Since Last Dose
Administration (Months)

Concentration Relative to
Steady State (%)a

1

2

50

2

3

25

3

4

12.5

4

5

6.3

aAssuming 1 month for galcanezumab half-life.

Management of Missed or Incomplete Loading Dose

The galcanezumab steady-state Cmax (Cmax, ss) at monthly doses of 120 mg is achieved after the 240 mg loading dose.1

Pharmacokinetic modeling of phase 3 data confirmed that

  • the 240-mg loading dose achieved steady-state galcanezumab concentrations by month 1 for the 120-mg monthly dose regimen, and
  • without a loading dose, the 120-mg monthly dose did not achieve steady state until 4 to 5 months.7,9

References

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

2Emgality [package leaflet]. Eli Lilly Nederland B.V., The Netherlands.

3Stauffer 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

4Skljarevski 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

5Detke 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

6Mulleners 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

7Data on file, Eli Lilly and Company and/or one of its subsidiaries.

8Kielbasa 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

9Kielbasa W, Quinlan T. Population pharmacokinetics of galcanezumab, an anti-CGRP antibody, following subcutaneous dosing to healthy individuals and patients with migraine. J Clin Pharmacol. 2020;60(2):229-239. http://dx.doi.org/10.1002/jcph.1511

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.

Date of Last Review: 12 May 2022


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