Emgality ® (galkanezumab)

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Emgality® ▼ (galcanezumab): Påverkan på funktion

Patienter som behandlades med galcanezumab upplevde kliniskt meningsfulla förbättringar i funktions-, funktionshinder och globala intryck jämfört med placebo.

Overview of Migraine Prevention Phase 3 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

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.

Measures of Functioning and Disability

The instruments used to measure patient global impressions, functioning, and disability in the phase 3 migraine prevention trials were

  • MSQ Version 2.1

  • MIDAS

  • PGI-S, and

  • PGI-I.5

The MSQ Role Function-Restrictive domain was considered the most relevant to measure treatment benefit related to the degree that performance of day-to-day activities is limited by migraine.6 The methods applied to the MSQ Role Function-Restrictive domain align with evidence requirements for an FDA label claim. 

For additional details about the instruments used, see Appendix.

Function and Disability at Baseline

Baseline function and disability are summarized in Table 1.

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

In the episodic migraine studies, the mean baseline scores on the

  • MSQ Role Function-Restrictive represent considerable functional impairment

  • MIDAS represent severe disability, and

  • PGI-S represent moderate illness severity.5

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

In the chronic migraine study, the mean baseline scores on the 

  • MSQ Role Function-Restrictive represents considerable functional impairment

  • MIDAS represents very severe disability, and

  • PGI-S represents marked illness severity.5

Table 1. Function and Disability Measures at Baseline5

Variable, mean (SD)

EVOLVE-1
N=858

EVOLVE-2
N=915

REGAIN
N=1113

Monthly MHD

9.13 (2.97)

9.13 (2.94)

19.41 (4.52)

MSQ Role Function-Restrictive Score

51.52 (16.03)

51.72 (15.62)

38.74 (17.23)

MIDAS Total Score

33.15 (27.66)

33.02 (29.73)

67.24 (57.31)

PGI-S

4.32 (1.12)

4.23 (1.20)

4.87 (1.25)

Abbreviations: MHD = migraine headache days; MIDAS = Migraine Disability Assessment; MSQ = Migraine-Specific Quality of Life Questionnaire Version 2.1; PGI-S = Patient Global Impression of Severity; SD = standard deviation.

Effect on Function and Disability

Changes on measures of function and disability are summarized in

In all 3 studies, patients treated with galcanezumab experienced less

  • functional impairment (measured by MSQ Role Function-Restrictive), and

  • disability (measured by MIDAS) compared with placebo.5,7

In all 3 studies, patient-rated instruments also showed greater

  • improvement in symptoms (PGI-I), and

  • reduction in illness severity (PGI-S).5,7

With the exception of the galcanezumab 240 mg dose in the chronic migraine study on the MIDAS, all doses of galcanezumab showed statistically significant differences compared with placebo on these measures.5

Furthermore, responder analyses were conducted based on the MSQ Role Function-Restrictive domain, MIDAS, and the PGI-S.5 

There were statistically significantly more patients meeting response thresholds for both doses of galcanezumab compared with placebo across all 3 studies on the

  • MSQ Role Function-Restrictive domain (58% to 70% in episodic migraine, and 64% to 65% in chronic migraine), and

  • MIDAS total score (73% to 80% in episodic migraine, and 45% to 49% in chronic migraine).5 

For the PGI-S, both doses of galcanezumab showed statistically significant improvement compared with placebo in both episodic migraine studies and directionally consistent improvement over placebo in the chronic migraine study.5

The consistent results over numerous assessments measuring functioning and disability and on the PGI-S and PGI-I further support the therapeutic benefit of galcanezumab in patients with episodic or chronic migraine.5,7

Episodic Migraine Prevention Studies

Table 2. EVOLVE-1: Measures of Functioning and Disability5,7

 

PBO
N=425

GMB 120 mg
N=210

GMB 240
N=208

LSMean Change from Baseline in:

MSQ Role Function-Restrictivea

24.69

32.43b

32.09b

MSQ Role Function-Preventivea

17.13

22.69b

21.81b

MSQ Emotional Functiona

20.73

29.03b

27.90b

MSQ Total Scorea

21.51

28.85b

28.22b

MIDAS Total Scorec

-14.87

-21.16b

-20.06d

PGI-Sa

-1.27

-1.59d

-1.55d

PGI-Ie

2.65

2.09b

2.11b

Mean % Responders Based on:

MSQ Role Function-Restrictiveaf

47%

63%b

70%b

MIDAS Total Scorecg

55%

80%b

76%b

PGI-Sah

34%

46%d

44%i

Abbreviations: GMB = galcanezumab; LSMean = Least Squares Mean; MIDAS = Migraine Disability Assessment; MSQ = Migraine-Specific Quality of Life Questionnaire Version 2.1; PBO = placebo; PGI-I = Patient Global Impression of Improvement; PGI-S = PGI of Severity.

a Results are for the average of months 4 to 6.

b p<.001 vs placebo.

c Results are at endpoint (ie, month 6).

d p<.01 vs placebo.

e Results are the average across the double-blind period (ie, months 1 to 6).

f Response defined as change from baseline ≥25.

g Response defined as improvement from baseline of 50%.

h Response defined as decrease from baseline of at least 2 points on the 7-point scale at the specific visit.

i p<.05 vs placebo.

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.

Table 3. EVOLVE-2: Measures of Functioning and Disability5,7


PBO
N=450

GMB 120 mg
N=226

GMB 240
N=220

LSMean Change from Baseline in:

MSQ Role Function-Restrictivea

19.65

28.47b

27.04b

MSQ Role Function-Preventivea

12.25

20.09b

18.91b

MSQ Emotional Functiona

15.60

24.10b

23.43b

MSQ Total Scorea

16.58

25.03b

23.88b

MIDAS Total Scorec

-12.02

-12.17b

-20.24b

PGI-Sa

-0.94

-1.22d

-1.17e

PGI-If

2.95

2.28b

2.36b

Mean % Responders Based on:

MSQ Role Function-Restrictiveag

43%

58%b

60%b

MIDAS Total Scorech

56%

73%b

77%b

PGI-Sai

29%

38%d

37%e

Abbreviations: GMB = galcanezumab; LSMean = Least Squares Mean; MIDAS = Migraine Disability Assessment; MSQ = Migraine-Specific Quality of Life Questionnaire Version 2.1; PBO = placebo; PGI-I = Patient Global Impression of Improvement; PGI-S = PGI of Severity.

a Results are for the average of months 4 to 6.

b p<.001 vs placebo.

c Results are at endpoint (ie, month 6).

d p<.01 vs placebo.

e p<.05 vs placebo.

f Results are the average across the double-blind period (ie, months 1 to 6).

g Response defined as change from baseline ≥25.

h Response defined as improvement from baseline of 50%.

i Response defined as decrease from baseline of at least 2 points on the 7-point scale at the specific visit.

Note: The recommended dose for the prophylaxis of migraine in adults who have at least 4 migraine days per month 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.

Chronic Migraine Prevention Study

Table 4. REGAIN: Measures of Functioning and Disability5

 

PBO
N=538

GMB 120 mg
N=273

GMB 240
N=274

LSMean Change from Baseline in:

MSQ Role Function-Restrictivea

16.76

21.81bc

23.05b

MSQ Role Function-Preventivea

10.98

17.98b

16.07b

MSQ Emotional Functiona

14.07

21.03b

20.70b

MSQ Total Scorea

14.55 

20.51b

20.49b

MIDAS Total Scorea

-11.53

-20.27d

-17.02

PGI-Sa

-0.62

-0.76

-0.91e

PGI-If

3.43

3.05b

2.99b

Mean % Responders Based on:

MSQ Role Function-Restrictiveag

54%

64%e

65%e

MIDAS Total Scoreah

36%

49%b

45%d

PGI-Sai

20%

24%

25%

Abbreviations: GMB = galcanezumab; LSMean = Least Squares Mean; MIDAS = Migraine Disability Assessment; MSQ = Migraine-Specific Quality of Life Questionnaire Version 2.1; PBO = placebo; PGI-I = Patient Global Impression of Improvement; PGI-S = PGI of Severity.

a Results at month 3.

b p<.001 vs placebo.

c Result not statistically significant after adjustment for multiplicity.

d p<.05 vs placebo.

e p<.01 vs placebo.

f Results are the average across the double-blind period (ie, months 1 to 3).

g Response defined as change from baseline ≥17.14.

h Response defined as improvement from baseline of 50%.

i Response defined as decrease from baseline of at least 2 points on the 7-point scale at the specific visit.

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. Jhingran P, Osterhaus JT, Miller DW, et al. Development and validation of the Migraine‐Specific Quality of Life Questionnaire. Headache. 1998;38(4):295-302. https://doi.org/10.1046/j.1526-4610.1998.3804295.x

7. Ford JH, Ayer DW, Zhang Q, et al. Changes in patient functioning and disability: results from two phase 3 double-blind placebo-controlled clinical trials evaluating galcanezumb for episodic migraine prevention (EVOLVE-1 and EVOLVE-2). Poster presented at: American Headache Society 60th Annual Scientific Meeting; June 27 - July 1, 2018; San Francisco, California.

8. Stewart WF, Lipton RB, Kolodner K, et al. Reliability of the Migraine Disability Assessment score in a population-based sample of headache sufferers. Cephalalgia. 1999;19(2):107-114. https://doi.org/10.1046/j.1468-2982.1999.019002107.x

9. Stewart WF, Lipton RB, Dowson AJ, Sawyer J. Development and testing of the Migraine Disability Assessment (MIDAS) Questionnaire to assess headache-related disability. Neurology. 2001;56 (suppl 1):S20-S28. http://dx.doi.org/10.1212/WNL.56.suppl_1.S20

10. Blumenfeld A, Varon S,Wilcox TK, et al. Disability, HRQoL and resource use among chronic and episodic migraineurs: results from the International Burden of Migraine Study (IBMS). Cephalalgia. 2011;31(3):301-315. http://dx.doi.org/10.1177/0333102410381145

11. Guy W. ECDEU assessment manual for psychopharmacology, revised 1976. Rockville (MD): National Institute of Mental Health, Psychopharmacology Research Branch; 1976:p 217-222. Available at: https://archive.org/details/ecdeuassessmentm1933guyw. Accessed August 1, 2018.

Glossary

FDA = Food and Drug Administration

MHD = migraine headache day

MIDAS = Migraine Disability Assessment

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

PGI-I = Patient Global Impression of Improvement

PGI-S = Patient Global Impression of Severity

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

MSQ

The MSQ instrument includes a 14-item questionnaire that measures 3 independent domains including

  • Role Function-Restrictive

  • Role Function-Preventive, and

  • Emotional Function.6

The MSQ measures the impact of migraine on

  • work or daily activities

  • relationships with family and friends

  • leisure time

  • productivity

  • concentration

  • energy

  • tiredness, and

  • emotional well-being.6

Scoring on each domain ranges from 0 to 100, with higher scores indicating better functioning.6 In other words, patients with higher scores on the MSQ experience fewer restrictions on the performance of day-to-day activities.

MIDAS

The MIDAS is a patient-rated scale that was designed to quantify migraine-related disability associated with missed or reduced productivity at work or home and social events.8,9

A higher value is indicative of more disability.8,9

Migraine-related disability categories derived from the total MIDAS score are

  • minimal or infrequent disability” for scores 0 to 5

  • mild or infrequent disability” for scores 6 to 10

  • moderate disability” for scores 11 to 20

  • severe disability” for scores 21 to 40, and

  • very severe disability” for scores 41 to 270.9,10

PGI-S and PGI-I

The PGI-S is a patient-rated instrument that measures the patient's global impression of the severity of their illness.11 Patients rated the question, “Considering migraine as a chronic illness, how would you rate the level of your illness,” on a scale ranging from 1 (“normal, not at all ill”) to 7 (“extremely ill”).

The PGI-I is a patient-rated instrument that measures the patient's global impression of symptom improvement.11 Patients were asked to respond to the prompt “Mark the box that best describes your migraine headache condition since you started taking this medicine using a range of responses from 1 (“very much better”) to 4 (“no change”) to 7 (“very much worse”).

Datum fӧr senaste ӧversyn 2018 M07 30


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