Emgality ® (galkanezumab)

För fullständig produktresumé för Emgality® se FASS.

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Försvinner effekten av Emgality® ▼ (galcanezumab) mot slutet av doseringsintervallet på 1 månad?

Posthoc -analyser av fas 3 -migränförebyggande studier visade att galcanezumab fungerar konsekvent under hela månaden och inte försvinner vid slutet av doseringsintervallet.

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Evaluating Consistency of Efficacy and Wearing Off

The recommended dose is 120 mg galcanezumab injected subcutaneously once monthly, with a 240 mg loading dose as the initial dose.1

Anecdotal reports suggest that some patients, more commonly those with high-frequency episodic migraine or chronic migraine, may experience an increase in migraine headache frequency toward the end of their calcitonin gene-related peptide monoclonal antibody dosing cycle.2

Dosing galcanezumab sooner than monthly in a patient that is experiencing increases in migraine headache frequency toward the end of the month has not been systematically studied.

Post hoc analyses from the phase 3 migraine prevention studies were conducted to

  • explore the consistency of galcanezumab 120 mg efficacy at each week throughout the monthly dosing interval at the treatment-population level3
  • define a threshold for wearing off of galcanezumab efficacy at the end of the month at the individual patient level,2 and
  • determine the incidence of wearing off in the galcanezumab migraine prevention studies (120 mg and 240 mg).2

Data from the

  • EVOLVE-1, EVOLVE-2, and REGAIN studies were used in the consistency of response analysis,3 and
  • EVOLVE-1, EVOLVE-2, REGAIN, and CONQUER studies were used in the wearing off analysis.2

  describes the clinical trials used in these post hoc analyses.

Consistent Efficacy Throughout the Monthly Dosing Interval

A post hoc analysis was conducted with pooled data from the EVOLVE-1, EVOLVE-2, and REGAIN phase 3 migraine prevention trials4-6 to evaluate the consistency of galcanezumab 120 mg (with an initial 240-mg loading dose) efficacy throughout the monthly dosing interval.3

Patients treated with galcanezumab 120 mg showed a statistically significantly greater average reduction from baseline in migraine headache days compared with placebo at each week of every month throughout double-blind periods of the studies (Change From Baseline in Weekly Migraine Headache Days Across All 6 Months: Episodic Migraineand Change From Baseline in Weekly Migraine Headache Days Across All 3 Months: Chronic Migraine ).3

In a day-by-day analysis, the estimated probability of having a migraine headache day on each day, averaged across all months was significantly lower in patients treated with galcanezumab 120 mg compared with placebo 

  • for all days 2 through 30 (p≤.001) in episodic migraine, and
  • on most days (p<.05) except for days 10, 23, and 29 (p=.091, p=.096, p=.125) in chronic migraine.3

In patients with episodic and chronic migraine treated with galcanezumab 120 mg,

  • there was no difference in weekly migraine headache days when the first week was compared to the fourth week of the month (episodic migraine p=.740; chronic migraine, p=.231), and
  • the estimated probability of having a migraine headache on days 2 and 30 were not different (episodic migraine, p=.61; chronic migraine, p=.616).3

Overall, according to a population-based analysis, which does not account for individual-level variations within a month, galcanezumab 120 mg efficacy was consistent throughout the dosing interval in patients with episodic or chronic migraine.3

Change From Baseline in Weekly Migraine Headache Days Across All 6 Months: Episodic Migraine3,7

Abbreviations: GMB = galcanezumab; LS = least squares; MMRM = mixed-model repeated measures.
* p<.001 vs placebo based on MMRM analysis.

Change From Baseline in Weekly Migraine Headache Days Across All 3 Months: Chronic Migraine3,7 

Abbreviations: GMB = galcanezumab; LS = least squares; MMRM = mixed-model repeated measures.
* p<.001 vs placebo based on MMRM analysis.

Efficacy Did Not Wear Off in Phase 3 Migraine Prevention Clinical Trials

An exploratory post hoc analysis of galcanezumab-treated patients in phase 3 migraine prevention clinical trials (EVOLVE-1, EVOLVE-2, REGAIN, and CONQUER) was conducted to

  • define a threshold of wearing off of efficacy at the end of the month at the individual patient level, and
  • determine the percentage of patients with high-frequency episodic migraine and chronic migraine who met the threshold of wearing off.2

Wearing off was defined as an increase in ≥2 migraine headache days per week in week 4 compared to week 2 of a treatment month for at least 2 months at the individual patient level.2

Individuals that were more likely to experience wearing off were included in this exploratory population-based analysis. This included those with

  • high-frequency episodic migraine (8 to <15 migraine headache days per month), or
  • chronic migraine (≥8 migraine headache days and ≥15 headache days per month).2

The rates of patients meeting the threshold of wearing off were not statistically significantly different between the

  • galcanezumab 120-mg and 240-mg treatment groups, and
  • placebo and either galcanezumab treatment groups.2

The percentage of patients who met the threshold of wearing off in the final week of the treatment cycle across treatment groups was

Less than 1% of patients experienced wearing off for at least 3 months (Percentage of Patients Meeting the Threshold of Wearing Off).2

Percentage of Patients Meeting the Threshold of Wearing Off2

Abbreviations: CM = chronic migraine; GMB = galcanezumab; HFEM = high-frequency episodic migraine; PBO = placebo.
*Patients with HFEM with an increase in 2 months were calculated out of 2 months for CONQUER (months 2 and 3) and out of 3 months for EVOLVE-1 and EVOLVE-2 (months 4, 5, and 6).

This post hoc analysis was in phase 3 clinical trials and therefore may not reflect real-world clinical experience. Other limitations of this post hoc analysis include

  • no consensus definition of wearing off, and
  • natural variation in migraine headache day frequency over time.2,7

References

1Emgality [summary of product characteristics]. Eli Lilly Nederland B.V., The Netherlands.

2Ailani J, Kuruppu DK, Rettiganti M, et al. Does wearing off of efficacy occur in galcanezumab-treated patients at the end of the monthly treatment cycle: a post hoc analysis of four phase 3 randomized trials. Cephalalgia. 2020;40(suppl 1):70. Migraine Trust Virtual 2020 - Digital presentations abstract MTV20-DP-058. https://doi.org/10.1177/0333102420962305

3Pozo-Rosich P, Samaan KH, Schwedt TJ, et al. Galcanezumab provides consistent efficacy throughout the dosing interval among patients with episodic and chronic migraine: a post hoc analysis. Adv Ther. Published online May 5, 2021. https://doi.org/10.1007/s12325-021-01708-8

4Detke 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

5Skljarevski 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

6Stauffer 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

7Data on file, Eli Lilly and Company and/or one of its subsidiaries.

8Mulleners WM, Kim BK, 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

Appendix: Phase 3 Migraine Prevention Studies

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)5,6
  • chronic migraine (REGAIN),4 and
  • episodic or chronic migraine that has not benefited from 2 to 4 previous migraine prevention medication categories (CONQUER).8
Summary of Study Design in the Migraine Prevention Studiesa

 

GMB Doses Studied

Study Duration

EVOLVE Studies5,6

120 mg monthlyb
or
240 mg monthly

6-month double-blind

REGAIN4

120 mg monthlyb
or
240 mg monthly

3-month double-blind,
with optional 9-month open-label extension

CONQUER8

120 mg monthlyb

3-month double-blind,
with optional 3-month open-label extension

Abbreviation: GMB = galcanezumab.

aAll studies were randomized, double-blind, and placebo-controlled.

bThe initial dose was administered as a 240-mg loading dose, followed by subsequent monthly doses of 120 mg.

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 2021 M03 23


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