Emgality ® (galkanezumab)

För fullständig produktresumé för Emgality® se FASS.

Denna information är endast avsedd för sjukvårdspersonal verksam i Sverige och som svar på din fråga. Informationen nedan är på engelska

Emgality® ▼ (galcanezumab): Effektivitet hos patienter som misslyckades med tidigare migränförebyggande behandling

Galcanezumab visade signifikant större minskningar av månatliga migrändagar jämfört med placebo, både hos patienter som misslyckades och inte misslyckades med ≥2 tidigare preventiva behandlingar av migrän.

Detailed Information

Galcanezumab has been studied in migraine prevention.1-3 A brief overview of the phase 3 double-blind, placebo controlled studies is provided in:Galcanezumab Clinical Trial Information.

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.

Subgroup Analyses in Patients Who Failed Prior Preventive Treatments For Migraine

Subgroup analyses of the primary outcomes and key secondary outcomes in EVOLVE-1, EVOLVE-2, and REGAIN were conducted among patients who

  • failed ≥2 prior preventives for efficacy and/or safety reasons

  • failed ≥1 prior preventive for efficacy and/or safety reasons, and

  • never failed preventives previously (including patients who had not taken any preventive previously and those who had taken a preventive but did not fail for efficacy reasons, safety reasons, or both).4,5

The number of preventive failures referred to the number of individual medications failed in the past 5 years and did not refer to classes of medications. Additionally, there was no restriction as to which types of medications could count as a treatment failure.4,5

Additional subgroups included

  • patients with 1 prior preventive failure for efficacy reasons, safety reasons, or both in EVOLVE-1 and EVOLVE-2,5 and

  • patients with ≥3 prior preventive failures for efficacy reasons, safety reasons, or both in REGAIN.4

Baseline disease characteristics in the episodic and chronic migraine studies are provided in: Table 1 and Table 2.

Table 1. Baseline Disease Characteristics: EVOLVE-1, EVOLVE-2 (Episodic Migraine)5

 

PBO
N=894

GMB 120 mg
N=444

GMB 240 mg
N=435

Migraine headache days per month, mean

9.1

9.0

9.0

Never failed prior preventives, mean

9.1

9.0

9.0

Failure of ≥1 medication, mean

9.2

9.5

9.4

Failure of ≥2 medications, mean

9.1

9.3

9.9

Failure of ≥3 medications, mean

---

---

---

Used Prior Preventive Treatment, %

62.1

65.3

61.8

Failure of ≥1 medication, %

24.8

28.8

23.9

Failure of ≥2 medications, %

10.3

11.5

10.3

Failure of ≥3 medications, %

4.0

6.8

4.1

Abbreviations: GMB = galcanezumab; PBO = placebo.

Table 2. Baseline Disease Characteristics: REGAIN (Chronic Migraine)1,4

 

PBO
N=558

GMB 120 mg
N=278

GMB 240 mg
N=277

Migraine headache days per month, mean

19.6

19.4

19.2

Never failed prior preventives, mean

19.6

18.8

19.3

Failure of ≥1 medication, mean

19.5

20.0

19.1

Failure of ≥2 medications, mean

19.6

20.0

19.0

Failure of ≥3 medications, mean

19.7

20.4

19.3

Used Prior Preventive Treatment, %

78.0

75.9

79.4

Failure of ≥1 medication, %

51.8

48.2

54.2

Failure of ≥2 medications, %

31.7

26.6

37.9

Failure of ≥3 medications, %

18.5

13.0

21.7

Abbreviations: GMB = galcanezumab; PBO = placebo.

In EVOLVE-1, EVOLVE-2, and REGAIN, antiepileptics, antidepressants, beta blockers, and calcium channel blockers were the most common preventive classes failed in the past 5 years.4,5

In EVOLVE-1 and EVOLVE-2, a majority of preventive failures were for topiramate (54.3%) followed by propranolol (20.8%) and amitriptyline (20.3%).5

In REGAIN, among individual medications failed, the most common included topiramate (57.6%), amitriptyline (31.4%), propranolol (26.7%), and botulinum toxin (17.3%).4

Change in Monthly Migraine Headache Days by Prior Preventive Failure Status

Across the EVOLVE-1 and EVOLVE-2 studies, both doses of galcanezumab were associated with statistically significantly higher reductions in mean monthly migraine headache days than placebo regardless of prior preventive failure subgroup: Table 3.5

In the REGAIN study, treatment with galcanezumab versus placebo resulted in statistically significant improvements in the number of monthly migraine headache days in patients with prior failures and for the 240 mg group in the subgroup with no prior preventive failures: Table 3.4 

In all 3 subgroups in EVOLVE-1 and EVOLVE-2, treatment with both doses of galcanezumab led to significantly (p<.05) larger reductions from baseline in the number of monthly migraine headache days at each month (1 to 6) versus placebo. Subgroup-by-treatment interactions were significant (p<0.05) for both galcanezumab doses versus placebo for comparison of subgroup with ≥1 prior failure versus no prior failure. This interaction was significant only for galcanezumab 240 mg versus placebo for comparison of subgroup with ≥2 prior failures versus no prior failure.5

In patients with ≥2 or ≥1 prior preventive failure in REGAIN, treatment with galcanezumab 120 mg versus placebo led to statistically significantly (p<.001) larger reductions in the number of monthly migraine headache days at each month of the treatment period (1 through 3). In patients treated with galcanezumab 240 mg, monthly migraine headache day reductions were significantly (p<0.05) larger versus placebo at months 1 and 3. In the subgroup of patients with no prior preventive failures, galcanezumab 240 mg versus placebo led to significant reductions (p<.01) at each month (1 through 3).4 Subgroup-by-treatment interactions were significant for the galcanezumab 120 mg versus placebo for the comparison of subgroups with ≥1 and ≥2 prior failures versus no prior failure.6

A larger placebo response in the no prior failure subgroup appeared to drive the smaller differences in this subgroup of patients in both the episodic and chronic migraine studies.4,5

Table 3. Overall Mean Change in Monthly Migraine Headache Days From Baseline4-6a

Treatment Subgroup

Failed ≥2 Prior Preventives

Failed ≥1 Prior Preventives

Never Failed Prior Preventivesb

EVOLVE-1 & EVOLVE-2 (Episodic Migraine)

PBO

N=90
-0.46

N=218
-1.30

N=657
-3.02

GMB 120 mg

N=51
-3.06c

N=126
-4.04cd

N=310
-4.72c

GMB 240 mg

N=45
-3.83ce

N=104
-4.21cd

N=324
-4.46c

REGAIN (Chronic Migraine)

PBO

N=174
-1.01

N=283
-2.02

N=254
-4.28

GMB 120 mg

N=72
-5.35cf

N=130
-5.53cg

N=142
-4.88

GMB 240 mg

N=104
-2.77h

N=146
-3.53h

N=127
-6.58c

Abbreviations: GMB = galcanezumab; PBO = placebo.

a Baseline migraine headache days per month are provided in the previous table.

b Includes patients who had not taken any preventive previously as well as those who had taken a preventive but did not fail for efficacy reasons, safety reasons, or both.

c p<.001 vs placebo.

d p<.05 vs placebo for comparison of subgroup with ≥1 prior failure vs no prior failure.

e p<.05 vs placebo for comparison of subgroup with ≥2 prior failures vs no prior failure.

f p<.001 vs placebo for comparison of subgroup with ≥2 prior failures vs no prior failure.

g p<.001 vs placebo for comparison of subgroup with ≥1 prior failure vs no prior failure.

h p<.01 vs placebo.

Key Secondary Outcomes by Prior Preventive Failure Status

Across all 3 studies, among patients with ≥1 or ≥2 prior preventive failures, a statistically significant greater proportion of galcanezumab-treated patients versus placebo (p<.001) experienced

  • 50% and ≥75% reduction in monthly migraine headache days on an average month

  • reductions in migraine headache days with acute medication use, and

  • improvements in patient functioning (Role Function-Restrictive domain score of the MSQ).4,5

These data are summarized in Table 4 and Table 5.

In EVOLVE-1 and EVOLVE-2, similar results were observed in patients with no prior preventive failures, however, there was a larger placebo response in this subgroup.5

In REGAIN, In the subgroup with no prior preventive failures, results were statistically significant for the

  • 240 mg galcanezumab dose versus placebo on all outcome measures, and

  • 120 mg galcanezumab dose versus placebo in the reduction in migraine headache days with acute medication use.4

Table 4. Key Secondary Outcomes by Prior Preventive Failure Status: EVOLVE-1 and EVOLVE-25

 

Failed ≥2 Prior Preventives

Failed ≥1 Prior Preventive

Never Failed Prior Preventivesa

Mean Percentage With ≥50% Reduction in Monthly Migraine Headache Daysbc

PBO

22.4%

26.5%

40.8%

GMB 120 mg

53.5%d

56.3%d

62.7%d

GMB 240 mg

61.0%d

60.5%d

58.1%d

Mean Percentage With ≥75% Reduction in Monthly Migraine Headache Daysbc

PBO

8.8%

11.5%

20.8%

GMB 120 mg

33.5%d

33.2%d

37.2%d

GMB 240 mg

39.2%d

36.2%d

36.3%d

LS Mean Change in Overall Monthly Migraine Headache Days With Acute Medication Use During the Treatment Periodc

PBO

-1.16

-1.04

-2.38

GMB 120 mg

-3.18e

-3.47d

-4.00d

GMB 240 mg

-3.86d

-3.63d

-3.77d

LS Mean Change From Baseline in MSQ RF-R Domain From Months 4-6

PBO

n=78
11.41

n=191
16.29

n=582
24.18

GMB 120 mg

n=50
24.38d

n=121
29.21d

n=281
31.05d

GMB 240 mg

n=43
24.89d

n=96
28.51d

n=298
29.74d

Abbreviations: GMB = galcanezumab; LS = least squares; MSQ RF-R = Migraine-Specific Quality of Life Questionnaire Role Function-Restrictive; PBO = placebo.

a Patients who had not taken any preventive previously and those who had taken a preventive but did not fail for efficacy reasons, safety reasons, or both.

b On an average month (30-day period within the 6-month treatment period).

c The number of patients is the same as provided above in "Overall Mean Change in Monthly Migraine Headache Days From Baseline."

d p<.001 vs placebo.

e p<.01 vs placebo.

Table 5. Key Secondary Outcomes by Prior Preventive Failure Status: REGAIN4

 

Failed ≥2 Prior Preventives

Failed ≥1 Prior Preventive

Never Failed Prior Preventivesa

Mean Percentage With ≥50% Reduction in Monthly Migraine Headache Daysb

PBO

9.4 %

11.3%

19.9%

GMB 120 mg

29.6%c

31.2%c

23.9%

GMB 240 mg

18.7%d

20.5%d

35.4%c

Mean Percentage With ≥75% Reduction in Monthly Migraine Headache Daysb

PBO

2.3%

2.7%

6.4%

GMB 120 mg

6.3%e

7.0%d

6.8%

GMB 240 mg

5.0%

6.0%e

11.7%e

LS Mean Change in Overall Monthly Migraine Headache Days With Acute Medication Use During the Treatment Periodb

PBO

-1.35

-1.94

-3.50

GMB 120 mg

-5.81c

-5.60c

-4.78e

GMB 240 mg

-3.40c

-3.66d

-5.83c

LS Mean Change From Baseline in MSQ RF-R Domain at Month 3

PBO

n=160
10.67

n=247
13.64

n=233
20.79

GMB 120 mg

n=64
19.13d

n=115
21.63c

n=133
23.45

GMB 240 mg

n=94
19.24d

n=131
19.22e

n=117
26.91d

Abbreviations: GMB = galcanezumab; LS = least squares; MSQ RF-R = Migraine-Specific Quality of Life Questionnaire Role Function-Restrictive; PBO = placebo.

a Patients who had not taken any preventive previously and those who had taken a preventive but did not fail for efficacy reasons, safety reasons, or both.

b The number of patients is the same as provided above in "Overall Mean Change in Monthly Migraine Headache Days From Baseline."

c p<.001 vs placebo.

d p<.01 vs placebo.

e p<.05 vs placebo.

Exploratory Outcomes

In EVOLVE-1 and EVOLVE-2, results in subgroup of patients with 1 prior failure were consistent with results observed in subgroups with ≥1 or ≥2 prior failure across outcomes.5

In REGAIN, results in a subgroup of patients with ≥3 prior preventive failures were consistent with results discussed above, with the exception of ≥75% response rate, which could not be evaluated.4

References

1. 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

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. 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. Ruff DD, Ford JH, Tockhorn-Heidenreich A, et al. Efficacy of galcanezumab in patients with chronic migraine and a history of preventive treatment failure. Cephalalgia. 2019;39(8):931-944. http://dx.doi.org/10.1177/0333102419847957

5. Ruff DD, Ford JH, Tockhorn-Heidenreich A, et al. Efficacy of galcanezumab in patients with episodic migraine and a history of preventive treatment failure: results from two global randomized clinical trials [published online November 6, 2019]. Eur J Neurol. http://dx.doi.org/10.1111/ene.14114

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

Glossary

MSQ = Migraine-Specific Quality of Life Questionnaire, Version 2.1

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

Galcanezumab 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),2,3 and

  • chronic migraine (REGAIN).1

The studies had a duration of

  • 6 months for prevention of episodic migraine,2,3 and

  • 3 months for prevention of chronic migraine, with an optional 9-month open-label extension phase.1 

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.1-3

Datum fӧr senaste ӧversyn 2019 M10 29


Kontakta Medicinsk Information på Lilly

Kontakta oss på telefon

Kontorstid vardagar 9.00-17.00

Eller så kan du

Klicka för att chatta är tillgänglig

Skriv din fråga till oss