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

Management of Missed or Delayed Doses

Patients should be instructed to inject a missed dose as soon as possible and then resume monthly dosing.¹

Do not take a double dose to make up for forgotten injection.²

 If you have forgotten to inject a dose of Emgality, inject the missed dose as soon as possible and then inject the next dose after a month from that date.²

Dose Administration 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 and

• chronic migraine (REGAIN).⁵

In the phase 3 clinical trials, injections were allowed to be administered within ±2 days of the scheduled visit.⁶

The recommended dose is 120 mg injected subcutaneously once monthly, with a 240 mg loading dose as the initial dose.⁶

Considerations for Repeating a Loading Dose After Missed Doses

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

The 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.⁶ It may require some time to re-establish steady-state galcanezumab plasma concentrations when dosing is resumed. Please consider the t_1/2 and PK characteristics of galcanezumab to determine whether a repeat loading dose is warranted.

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

• T_max of 5 days, and

• t_1/2 of 27 days.^1,7

Steady state concentrations are achieved by month 1 for the 120-mg monthly dose with a 240-mg loading dose.⁷ 

After missing 3 consecutive monthly doses, approximately 12% of the galcanezumab concentration relative to steady-state will be remaining (Table 1).⁶ 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.

Table 1. Effect of Missed Monthly Doses on Galcanezumab Steady State Concentrations⁶

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

^a Assuming 1 month for galcanezumab half-life.

Management of Missed or Incomplete Loading Dose

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

In the phase 2 dose-ranging study, a loading dose was not implemented.⁸ In that study, the galcanezumab 120 mg dose did not achieve statistically significant separation from placebo in mean change from baseline migraine headache days until month 3.

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/month dose regimen.⁶

In the event of a missed or incomplete loading dose, complete the loading dose as soon as possible. Then continue with the monthly maintenance dose from the date of last dose.

Therapeutic Indication

Galcanezumab is indicated for the prophylaxis of migraine in adults who have at least 4 migraine days per month.¹

References

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

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

3. 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

4. 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

5. 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

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

7. 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

8. Skljarevski V, Oakes TM, Zhang Q, et al. Effect of different doses of galcanezumab vs placebo for episodic migraine prevention: a randomized clinical trial. JAMA Neurol. 2018;75(2):187-193. http://dx.doi.org/10.1001/jamaneurol.2017.3859

Glossary

PK = pharmacokinetics

t_1/2 = elimination half-life

T_max = time of maximum observed drug concentration

▼ 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.