Emgality® ▼ (galcanezumab): Respons i kliniska studier av migränförebyggande

Description of Phase 3 Migraine Prevention Program

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)^1,2

• chronic migraine (REGAIN),³ and

• episodic or chronic migraine that has not benefited from 2 to 4 previous migraine prevention medication categories (CONQUER).⁴

Galcanezumab has also been studied in a phase 3, open-label, 12-month safety study (CGAJ) for the prevention of episodic or chronic migraine.⁵

The galcanezumab doses used and duration of the migraine prevention studies are summarized in Table 1.

Table 1. Summary of Study Design in the Migraine Prevention Studies^a

	GMB Doses Studied	Study Duration
EVOLVE Studies1,2	120 mg monthlyb or 240 mg monthly	6 months double-blind
REGAIN3	120 mg monthlyb or 240 mg monthly	3 months double-blind, with optional 9-month open-label extension
CONQUER4	120 mg monthlyb	3 months double-blind,  with optional 3-month open-label extension
CGAJ5	120 mg monthlyb or 240 mg monthly	12 months open-label

Abbreviation: GMB = galcanezumab.

^a With the exception of study CGAJ, all studies were randomized, double-blind, and placebo-controlled.

^b The initial dose was administered as a 240 mg loading dose, followed by subsequent monthly doses of 120 mg.

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

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

• 6 months for the EVOLVE-1 and EVOLVE-2 studies,^1,2 and

• 3 months for the REGAIN and CONQUER studies.^3,4

In the 12-month, open-label, safety study, the primary endpoint was the long-term safety and tolerability of galcanezumab for up to 12 months of treatment.⁵

Response Rates Analysis

Response rates were a key secondary endpoint in all studies, and defined as the mean percentage of patients meeting prespecified monthly migraine headache day reductions from baseline at thresholds of ≥50%, ≥75%, or 100% on an average month, across

• months 1 to 6 in the EVOLVE studies^1,2

• months 1 to 3 in the REGAIN and CONQUER studies,^3,4 and

• months 1 to 12 in study CGAJ.⁵

A 50% response rate is viewed as clinically significant for episodic migraine.⁷

A response threshold of ≥30% was included as an additional secondary analysis because 30% is viewed as clinically significant response rate for chronic migraine.⁸

Percentage of Patients Achieving Response Rate Thresholds

Baseline monthly migraine headache days experienced by patients were

• 9.1 days in the EVOLVE studies⁹

• 19.4 days in the REGAIN study,³ and

• 13.2 days in the CONQUER study.⁴

The baseline monthly migraine headache days were comparable between treatment groups in those studies.^1-4

In study CGAJ, at baseline, patients in the galcanezumab 240-mg group had a greater number of monthly migraine headache days compared with the galcanezumab 120-mg group (11.4 vs 9.7 days, p<.05).⁵

In the placebo-controlled studies, galcanezumab was superior to placebo in the mean percentage of patients experiencing clinically meaningful reductions from baseline, on an average month, in monthly migraine headache days at thresholds of

• ≥50%, ≥75%, and 100% in the EVOLVE-1, EVOLVE-2, and CONQUER studies,^1,2,4 respectively, and

• ≥30% and ≥50% in the REGAIN study (Table 2).^3,10

Note that 30% response rate was not included in the multiple testing procedure.¹⁰

Response rates for CGAJ are also summarized in Table 2, although there was no placebo-comparison in that study.⁵

Table 2. Mean Percentages of Patients With Reductions in Number of Monthly Migraine Headache Days^1-5,10

	Estimated RR ≥30%a	Estimated RR ≥50%	Estimated RR ≥75%	Estimated RR 100%
EVOLVE-1b
Placebo (N=425)	56.8	38.6	19.3	6.2
GMB 120 mg (N=210)	77.1c	62.3c	38.8c	15.6c
GMB 240 mg (N=208)	74.3c	60.9c	38.5c	14.6c
EVOLVE-2b
Placebo (N=450)	52.7	36.0	17.8	5.7
GMB 120 mg (N=226)	73.4c	59.3c	33.5c	11.5c
GMB 240 mg (N=220)	72.6c	56.5c	34.3c	13.8c
REGAINd
Placebo (N=538)	32.3	15.4	4.5	0.5
GMB 120 mg (N=273)	44.8c	27.6c	7.0ef	0.7
GMB 240 mg (N=274)	46.4c	27.5c	8.8c	1.3
CONQUERdg
Placebo (N=228)	NAh	13.3	3.3	0.0
GMB 120 mg (N=230)	NAh	37.7i	14.5i	4.9i
CGAJjk
GMB 120 mg (N=135)	76.1	65.6	44.5	21.4
GMB 240 mg (N=135)	80.9	73.7	52.5	21.8

Abbreviations: GMB = galcanezumab; NA = not applicable; RR = response rate.

^a The ≥30% RR was not part of the multiple testing procedure, so none of the p values for this RR were adjusted for multiplicity; the other 3 RR were part of the multiple testing procedure. Multiplicity protects against inadvertent findings of significance due to multiple comparisons.

^b Months 1-6.

^c p<.001 vs placebo.

^d Months 1-3.

^e p<.05 vs placebo.

^f Not significant after adjustment for multiplicity.

^g Overall results combined for patients with episodic or chronic migraine.

^h A 30% RR was not measured for the overall population that included patients with episodic or chronic migraine. 

ⁱ p<.0001 vs placebo.

^j Months 1-12.

^k No multiplicity adjustment was conducted for this study.

Monthly Response Rate Analyses for ≥50%

Response rate at each month was defined as the percentage of patients meeting a defined threshold in the reduction from baseline in the number of migraine headache days for that month.¹⁰ These rates are shown below for

• EVOLVE-1 (Figure 1)

• EVOLVE-2 (Figure 2)

• REGAIN (Figure 3)

• CONQUER (Figure 4), and

• CGAJ (Figure 5).

Figure 1. EVOLVE-1: Monthly ≥50% Response Rates¹⁰

Abbreviation: GMB = galcanezumab.
*** p<.001 vs placebo.
^a For a specific month, represents the number of intent-to-treat subjects who have nonmissing baseline value and at least one postbaseline value.
Note: No multiplicity adjustment was conducted for response rate at a specific month.

Figure 2. EVOLVE-2: Monthly ≥50% Response Rates¹⁰

Abbreviation: GMB = galcanezumab.
*** p<.001 vs placebo.
^a For a specific month, represents the number of intent-to-treat subjects who have nonmissing baseline value and at least one postbaseline value.
Note: No multiplicity adjustment was conducted for response rate at a specific month.

Figure 3. REGAIN: Monthly ≥50% Response Rates¹⁰

Abbreviation: GMB = galcanezumab.
** p<.01 vs placebo.
*** p<.001 vs placebo.
^a For a specific month, represents the number of intent-to-treat subjects who have nonmissing baseline value and at least one postbaseline value.
Note: No multiplicity adjustment was conducted for response rate at a specific month.

Figure 4. CONQUER: Monthly ≥50% Response Rates¹⁰

Abbreviation: GMB = galcanezumab.
*** p<.0001 vs placebo.
^a For a specific month, represents the number of intent-to-treat subjects who have nonmissing baseline value and at least one postbaseline value.
Note: No multiplicity adjustment was conducted for response rate at a specific month.

Figure 5. CGAJ: Monthly ≥50% Response Rates¹⁰

Abbreviation: GMB = galcanezumab.
* p≤.05 vs GMB 120 mg.
^a For a specific month, represents the number of intent-to-treat subjects who have nonmissing baseline value and at least one postbaseline value.
Note: No multiplicity adjustment was conducted for response rate at a specific month.

Therapeutic Indication

Galcanezumab is indicated for the prophylaxis of migraine in adults who have at least 4 migraine days per month.⁶

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

References

1. 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

2. 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

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. Mulleners WM, Kim B-K, 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

5. Camporeale A, Kudrow D, Sides R, et al. A phase 3, long-term, open-label safety study of galcanezumab in patients with migraine. BMC Neurol. 2018;18(1):188. http://dx.doi.org/10.1186/s12883-018-1193-2

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

7. Tfelt-Hansen P, Block G, Dahlof C, et al. Guidelines for controlled trials of drugs in migraine: second edition. Cephalalgia. 2000;20(9):765-786. http://dx.doi.org/10.1046/j.1468-2982.2000.00117.x

8. Silberstein S, Tfelt-Hansen P, Dodick DW, et al. Guidelines for controlled trials of prophylactic treatment of chronic migraine in adults. Cephalalgia. 2008;28(5):484-495. http://dx.doi.org/10.1111/j.1468-2982.2008.01555.x

9. Detke HC, Millen BA, Zhang Q, et al. Rapid onset of effect of galcanezumab for the prevention of episodic migraine: analysis of the EVOLVE studies. Headache. 2020;60(2):348-359. http://dx.doi.org/10.1111/head.13691

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

Glossary

CM = Chronic Migraine

EM = Episodic Migraine

MHD = migraine headache day

▼ 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.