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

Detailed Information

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 and

• chronic migraine (REGAIN).³

The studies had a duration of

• 6 months for prevention of episodic migraine,^1,2 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.^1-3 

• The recommended dose is 120 mg galcanezumab injected subcutaneously once monthly, with a 240 mg loading dose as the initial dose.⁴ 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 MHDs over

• 6 months for episodic migraine, and

• 3 months for chronic migraine.^1-3

Response Rates Analysis

Response rates were

• a key secondary endpoint in all 3 studies, and

• defined as the mean percentage of patients meeting pre-specified monthly MHD reduction from baseline thresholds of ≥50%, ≥75%, or 100% on an average month, across the double-blind treatment period.⁵

A 50% response rate is viewed as clinically significant for episodic migraine.⁶

A response threshold of ≥30% was included as an additional secondary analysis because 30% is viewed as clinically significant response rate for chronic migraine.⁷

Response Rates

Patients in the episodic migraine studies, EVOLVE-1 and EVOLVE-2, had a baseline mean of 9.1 MHDs per month.⁵

Patients in the chronic migraine study, REGAIN, had baseline mean of 19.4 MHDs per month.⁵

All 3 studies demonstrated that both doses of galcanezumab are superior to placebo in the mean percentage of patients experiencing clinically meaningful reductions from baseline, on an average month, in monthly MHDs at thresholds of

• ≥50%, ≥75%, and 100% over 6 months for patients with episodic migraine, and

• ≥30% and ≥50% over 3 months for patients with chronic migraine (Table 1).⁵

Note that 30% response rate was not included in the multiple testing procedure.⁵

In the chronic migraine study, only the 240-mg dose of galcanezumab was statistically significantly superior to placebo for ≥75% response after the multiplicity adjustment, and neither dose separated from placebo for rates of 100% response over 3 months.⁵

Table 1. Mean Percentages of Patients With Reductions in Number of Monthly Migraine Headache Days - Phase 3 Placebo-controlled Analysis Set^1-3,5

	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

Abbreviations: GMB = galcanezumab; RR = response rate.

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

^b Months 1 to 6.

^c p<.001 vs. placebo.

^d Months 1 to 3.

^e p<.05 vs. placebo.

^f Not significant after adjustment for multiplicity.

Note: The recommended dose is 120 mg galcanezumab injected subcutaneously once monthly, with a 240 mg loading dose as the initial dose .⁴ 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.

Therapeutic Indication

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

The recommended dose is 120 mg galcanezumab injected subcutaneously once monthly, with a 240 mg loading dose as the initial dose.⁴

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

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

6. 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

7. 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

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.