Emgality ® (galkanezumab)

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Emgality®▼ (galcanezumab): Effekt och säkerhet med avseende på ålder i migränförebyggande prövningar

Effekt och säkerhet av galcanezumab var jämförbar mellan åldersgrupper upp till 65 år, i migränförebyggande fas 3-studier.

Detailed 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.

No dose adjustment is needed on the basis of age (18 to 65 years), sex, weight, race or ethnicity as there was no clinically meaningful effect of these factors on the apparent clearance or apparent volume of distribution of galcanezumab.1

There is limited information in subjects aged ≥ 65 years.1

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).4

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.4 

Patients in EVOLVE-1, EVOLVE-2, and REGAIN were required to be between the ages of 18 to 65 years, inclusive, at the time of screening.2-4 

Patients > 65 years of age were also excluded.1

Efficacy by Age - Phase 3 Double-blind, Placebo-controlled Studies

Across the 3 studies, patients were predominantly female (> 83 %) with a mean age of 41 years, and an average migraine history of 20 to 21 years.1

The efficacy of galcanezumab was evaluated across 4 age categories (years) including

  • 40

  • >40 to ≤50

  • >50 to ≤55, and

  • >55 to ≤65.5

Baseline MHDs

No pattern suggesting that frequency of monthly MHDs increases with age was observed. The number of baseline MHDs across age groups was similar, with

  • about 9 MHDs in episodic migraine, and

  • about 19 MHDs in chronic migraine: Table 1.2

Table 1. Baseline Number of Monthly Migraine Headache Days by Age - Phase 3 Double-Blind, Placebo-Controlled Migraine Prevention Trials5

Age (years)

N

Monthly MHD Mean

N

Monthly MHD Meana


EVOLVE-1 and EVOLVE-2

REGAIN

40

820

9.3

524

19.8

>40 - ≤50

536

9.1

313

19.3

>50 - ≤55

208

8.9

128

18.4

>55 - ≤65

209

8.8

148

19.2

Abbreviation: MHD = migraine headache day.

a Significant difference between age groups for monthly MHD in REGAIN (p value=.006), for which patients in the >50 to ≤55 group appeared to have a lower mean baseline monthly migraine headache days.

Analyses of Primary and Secondary Outcome Measures

The galcanezumab clinical trial data were examined for the effects of age within the age range enrolled in the studies. Overall, findings demonstrated that age, up to 65 years, did not have an effect on galcanezumab efficacy.5

Age was not a stratification factor in the phase 3 migraine prevention studies, resulting in some imbalances of age subgroups across the treatment arms in the pooled analysis of EVOLVE-1 and EVOLVE-2. However, the subgroup analysis appropriately accounts for the age main effect in the model to adjust for potential confounding.6 

The only statistically significant treatment-by-subgroup interaction was in change from baseline in MHDs with acute medication use in the episodic migraine studies, for which older patients appeared to have a larger reduction than younger patients ( ).5

Safety by Age - Phase 3 Double-blind, Placebo-controlled Studies

The safety of galcanezumab was evaluated across 4 age categories (years), including

  • <42

  • 42 to <50

  • 50 to <60, and

  • 60 to ≤65.5

Frequency of SAEs and Discontinuations Due to an AE

Data do not indicate an increased frequency in galcanezumab-treated patients 60 to ≤65 years of age in

  • TEAEs

  • SAEs overall, or in CV SAEs in particular

  • discontinuations due to AEs overall, or

  • discontinuations due to AEs likely to be CV in nature ( ).5,6

Exposure-Adjusted Incidence Rates of TEAEs

Exposure-adjusted incidence rates are a measure of whether TEAEs occur at an increased frequency with increased treatment duration.6

In EVOLVE-1, EVOLVE-2, and REGAIN, no treatment-by-age subgroup interaction was observed for EAIRs for TEAEs. When compared with a larger pool of galcanezumab-treated patients from phase 2 and phase 3 studies, the EAIRs for TEAEs were consistent across age groups and there was no trend of an increase with increased treatment duration.6

Cardiovascular Safety

No galcanezumab-treated patient in the 60 to ≤65 years age group

  • experienced a CV SAE, or

  • discontinued due to an AE likely to be CV in nature.6

Increasing age among patients treated with galcanezumab versus placebo was not associated with greater frequencies of hypertension or high blood pressure:  .5,6

Exposure-Adjusted Incidence Rates Related to Cardiovascular Safety

There was not a significant treatment-by-age subgroup interaction for TEAEs likely to be CV in nature in EVOLVE-1, EVOLVE-2, and REGAIN. When compared with a larger pool of galcanezumab-treated patients from phase 2 and phase 3 studies, the EAIRs for each age subgroup were consistent with or slightly less than the respective incidence rates for the age groups in EVOLVE-1, EVOLVE-2, and REGAIN.6

There were not significant treatment-by-age subgroup interactions for increase in

  • systolic blood pressure (any post-baseline measurement ≥140 mmHg and ≥20 mmHg increase from baseline), or

  • diastolic blood pressure (any post-baseline measurement ≥90 mmHg and ≥10 mmHg increase from baseline).5

Pharmacokinetics by Age

Pharmacokinetic data were obtained from patients in

  • EVOLVE-1 (N=422)

  • EVOLVE-2 (N=447)

  • REGAIN (N=545),  and

  • a phase 2 study, CGAB (N=266).5

Age (18 to 65 years) did not affect galcanezumab clearance (CL/F) in patients with migraine.5

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. 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

3. 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

4. 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

5. Stauffer VL, Turner I, Kemmer P, et al. Effect of age on efficacy and safety of galcanezumab treatment in adult patients with migraine. Poster presented at: 71st Annual Meeting of the American Academy of Neurology (AAN); May 4-10, 2019; Philadelphia, PA.

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

Glossary

AE = adverse event

CV = cardiovascular

EAIR = exposure-adjusted incidence rate

MHD = migraine headache day

SAE = serious adverse event

SMQ = standard MedDRA query

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.

Datum fӧr senaste ӧversyn 2019 M05 21


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