Emgality® ▼ (galcanezumab): Use With Migraine Preventives

Additional Information

Study REGAIN had a 3 month, double-blind, placebo-controlled treatment period followed by a 9 month open-label extension. Approximately 15 % of the patients continued concurrent treatment with topiramate or propranolol as allowed by the protocol for prophylaxis of migraine.¹

Please note that the results of a maintenance dose of 240 mg galcanezumab once monthly are also included in this response. Even though this dose has been tested in pivotal studies, it has not been approved and therefore is not recommended.

Concomitant Use With Migraine Preventives in a Phase 3 Study for Chronic Migraine

An overview of migraine phase 3 clinical trials are provided in Appendix: Clinical Trial Information

In general, patients were not allowed to continue on prior migraine prophylactic therapies.^2,3 However, up to 33% of patients in the chronic migraine prevention trial were allowed to continue migraine prophylactic treatment with either topiramate or propranolol if

• the patient has been on a stable dose for at least 2 months prior to the prospective baseline period, and

• dosing will remain stable throughout the double-blind treatment period.^2,3

In this study, 14.6% of patients were concomitantly using either topiramate (10.1%) or propranolol (4.5%) for migraine prophylaxis.^2,3

Safety Analysis for Concomitant Prophylaxis Subgroups

The safety profile, including common TEAEs, vital signs, and weight, by baseline concurrent prophylaxis use subgroup (yes/no) was analyzed to assess whether there was a differential treatment effect of galcanezumab compared to placebo among the subgroup of patients with concurrent prophylaxis use versus the subgroup of patients without concurrent prophylaxis use.²

Vital Sign Changes by Concomitant Prophylaxis Subgroup

Analysis of vital signs and weight by concurrent prophylaxis subgroups (yes/no) found no interaction between concurrent prophylaxis use and treatment group on

• pulse,

• temperature, or

• weight.²

There was a statistically significant interaction between concomitant prophylaxis and treatment group on both SBP and DBP.²

For SBP, the difference in overall least squares mean change between the galcanezumab 240-mg dose group and placebo were

• -3.62 mm Hg for the “yes” concurrent prophylaxis use group (p=.026 vs placebo), and

• -0.03 mm Hg for the “no” concurrent prophylaxis group.²

A similar pattern was observed for DBP, with a least squares mean difference between the galcanezumab 240-mg dose group and placebo of

• -4.26 mm Hg for the “yes” concurrent prophylaxis use group (p<.001 vs placebo), and

• 0.20 mm Hg for the “no” concurrent prophylaxis group.²

Results should be interpreted with caution due to the relatively small sample size for the concurrent prophylaxis use "yes" group (n=157).²

Although the SBP and DBP decreases in patients with concomitant prophylaxis was statistically significant for the group mean change analysis, only 3 of the 80 galcanezumab-treated patients (all received galcanezumab 240 mg) had a treatment-emergent decrease in either SBP or DBP or both at 1 time point. Of the 3 patients,

• 2 were receiving concomitant propranolol, and

• 1 was receiving concomitant topiramate.²

The decrease was not sustained and did not result in an AE of hypotension being reported. Therefore, these findings were likely not clinically meaningful.²

Treatment-Emergent Adverse Events  by Concomitant Prophylaxis Subgroup

Subgroup analysis of common TEAEs by baseline concurrent prophylaxis use did not indicate any clinically meaningful differences in incidence of these AEs in patients with or without concurrent prophylaxis use.^2,4 

Based on these results, concomitant use of prophylaxis does not have an effect on the safety of galcanezumab.²

Efficacy Analysis for Concomitant Prophylaxis Subgroups

An analysis of mean change from baseline in the number of monthly migraine headache days by concomitant prophylaxis use for the subset of patients who were using concomitant topiramate or propranolol showed an overall mean reduction in the number of monthly migraine headache days across months 1 to 3 (Table 1).²

Table 1. Change From Baseline in Number of Monthly Migraine Headache Days^a by Concurrent Prophylaxis Use²

Abbreviations: GMB = galcanezumab; N/A = not applicable; PBO = placebo.

^a Across months 1 to 3.

^b Least squares mean change from baseline.

There was no statistically significant treatment-by-subgroup interaction in concurrent prophylaxis users.² This subgroup was small, with insufficient power to detect a difference versus placebo. However, the differences observed between galcanezumab and placebo were directionally consistent, although smaller in magnitude, than those observed in patients not receiving concomitant prophylaxis.²

For patients not using concomitant topiramate or propranolol, the overall mean reduction in the number of monthly migraine headache days across months 1 to 3 is also summarized in Table 1.²

Although galcanezumab did not seem to provide as much benefit to patients receiving concomitant prophylaxis as it did to those given monotherapy, some improvements were observed. However, this subgroup was small, and these results may be confounded by selection bias. This population comprised patients who were already taking concomitant prophylaxis and yet agreed to participate in a clinical trial, which may signal that they were more difficult to treat.²

A review of this population at baseline showed that they had had migraine diagnoses for longer than the rest of the population (average of 23.0 years for patients taking concomitant prophylaxis versus 20.8 years for patients not taking it), also indicating that they may be a difficult to treat group.²

Concomitant Use With Migraine Preventives in Phase 3 Studies for Episodic Migraine

Use of migraine preventive medications was not allowed in the episodic migraine clinical trials.^5,6

The decision to administer galcanezumab in combination with migraine preventives must be based on the clinical judgment of the prescribing healthcare practitioner after careful consideration of the patient's risk factors as well as the risks and benefits of treatment. The decision remains at the discretion of the prescribing physician.

Therapeutic Indication

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

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

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. 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

4. Bangs ME, Kudrow D, Wang S, et al. Safety and tolerability of monthly galcanezumab injections in patients with migraine: integrated results from migraine studies. BMC Neurology. 2020;20(1):25. http://dx.doi.org/10.1186/s12883-020-1609-7. Published correction appears in BMC Neurology. 2020;20(1):90. http://dx.doi.org/10.1186/s12883-020-01675-7

5. 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

6. 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

Glossary

AE = adverse event

DBP = diastolic blood pressure

SBP = systolic blood pressure

TEAE = treatment-emergent adverse event

▼ 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.

Appendix: Clinical Trial Information

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),^5,6 and

• chronic migraine (REGAIN).³

The studies had a duration of

• 6 months for prevention of episodic migraine,^5,6 and

• 3 months for prevention of chronic migraine, with an optional 9-month open-label extension phase.³ 

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.^3,5,6 

The primary endpoint was the overall mean change from baseline in the number of monthly migraine headache days over

• 6 months for episodic migraine, and

• 3 months for chronic migraine.^3,5,6

In these studies, the 240 mg galcanezumab dose was not observed to be more efficacious overall than the 120 mg dose.² Therefore, the recommended dose is 120 mg injected subcutaneously once monthly, with a 240 mg loading dose as the initial dose.