Emgality ® (galkanezumab)

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Emgality® ▼ (galcanezumab): Behandlingsrelaterad viktminskning

Procentandelen av galcanezumab-behandlade patienter i fas 3-studier med viktminskning var antingen lika med eller lägre än placebo, utan några statistiskt signifikanta eller kliniskt signifikanta skillnader mellan grupperna.

Description of Analyses

Galcanezumab has been studied in migraine prevention.1-5 Treatment-emergent weight loss during the double-blind treatment phases of the migraine prevention are summarized separately below.

Note: Galcanezumab is indicated for the prophylaxis of migraine in adults who have at least 4 migraine days per month. The recommended dose is 120 mg galcanezumab injected subcutaneously once monthly, with a 240 mg loading dose as the initial dose.6 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.

Additional details on the studies are available in the  .

Information from the SmPC

Weight loss is not mentioned in the list of adverse reactions in clinical studies and post-marketing reports of the summary of product characteristics of Emgality.6

Summary of Treatment-Emergent Weight Loss in Phase 3 Migraine Prevention Studies

The EVOLVE-1, EVOLVE-2, and REGAIN studies were the pivotal studies and safety results have been integrated resulting in a pooled analysis of 2886 adult patients, comprised of a total of 1435 patients that received monthly doses of galcanezumab (120 mg or 240 mg) administered subcutaneously.7

Results from CONQUER and the phase 3 open-label safety study are provided to supplement the primary integrated safety analysis. In the CONQUER study, there was a total of 462 adult patients enrolled, with 232 patients that received monthly doses of galcanezumab 120 mg.4 In the 12-month open-label safety study, a total of 270 adult patients received monthly doses of galcanezumab (120 or 240 mg).5

Treatment-emergent low weight is defined as categorical changes of ≥7.0% loss of body weight from baseline.8 This parameter was evaluated in all studies.

Weight Loss in the Placebo-Controlled Studies

The mean changes in weight were small and not clinically meaningful in the

  • integrated safety analysis of the EVOLVE-1, EVOLVE-2, and REGAIN studies, and

  • CONQUER study.8

The mean weight change from baseline was

  • -0.03 kg (-0.07 lb) for both galcanezumab dose groups in the EVOLVE-1, EVOLVE-2 and REGAIN studies and -0.02 kg (-0.04 lb) for placebo, and

  • 0.15 kg (0.33 lb) for galcanezumab 120 mg in the CONQUER study and was 0.21 kg (0.46 lb) for placebo.8

These changes were small and not clinically meaningful.

A similar proportion of galcanezumab-treated patients and placebo lost ≥7.0% of their baseline weight, with no statistically significant changes observed between treatment groups ( ).7,8 

Table 1. Categorical Decrease in Weighta During Double-Blind Treatment in the EVOLVE-1, EVOLVE-2, REGAIN, and CONQUER Studies7,8

 

N

Frequency
n (%)

EVOLVE-1, EVOLVE-2, REGAIN Integrated Safety Analysis

   PBO

1333

34 (2.6)

   GMB 120 mg

669

26 (3.9)

   GMB 240 mg

684

23 (3.4)

CONQUER

   PBO

225

3 (1.3)

   GMB 120 mg

226

1 (0.4)

Abbreviations: GMB = galcanezumab; PBO = placebo.

a Defined as a ≥7.0% decrease in body weight from baseline.

Weight Decrease in the 12-Month, Open-Label Study: CGAJ

In study CGAJ, the mean changes from baseline to last-observation-carried-forward endpoint in weight were small for both treatment groups combined (≤1 kg) and were not considered to be clinically meaningful across the 1-year of treatment.5,8

The percentage of galcanezumab-treated patients who met the categorical criteria for treatment-emergent low weight was 9.8% (Table 2).8

There were no meaningful differences between the 120-mg and 240-mg treatment groups.8 There does not appear to be any clinically meaningful impact of galcanezumab on weight given that

  • weight changes may be anticipated over the course of a 12-month study 

  • the observed categorical weight changes occurred in both directions (weight loss and weight gain), and

  • there was an observed plateau effect on weight in the 6 to 12 month period.8

Table 2. Categorical Decreasesa in Weight: CGAJ Study5,8

 

GMB 120 mg
N=123
n (%)

GMB 240 mg
N=131
n (%)

GMB Pooled
N=254
n (%)

Frequency, n (%)

13 (10.6)

12 (9.2)

25 (9.8)

Abbreviations: GMB = Galcanezumab; GMB Pooled = GMB 120 mg and GMB 240 mg pooled.

a Defined as a ≥7.0% decrease in body weight from baseline.

Discontinuation Due to Weight Loss

No patients discontinued due to weight loss in any of these studies.8

Postmarketing Spontaneous Reports

Based on postmarketing spontaneous reports in the Eli Lilly and Company spontaneous AE database through 27 March 2020, the MedDRA terms of

  • weight decreased was rarely reported, and

  • weight fluctuation was very rarely reported.8

Rarely reported is defined as an AE that has been reported at an estimated rate of ≥0.01% and <0.1% according to the reporting system information.8 Very rarely reported is defined as an AE that has been reported at an estimated rate of <0.01% according to the reporting system information.

Postmarketing data do not necessarily represent the rate of occurrence of an AE in a treated population, but they represent a reporting rate of a particular AE to the company. Spontaneous reporting of AEs can be highly variable and is not appropriately controlled clinical information on which to base an assessment of whether a particular drug product is the causal agent of an event.9

Spontaneous reporting has limited use due to

  • lack of control population

  • under-reporting or reporting bias, and

  • missing or incomplete information regarding medical history or concomitant medications.9

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. Mulleners 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

5. Camporeale A, Kudrow D, Sides R, et al. A phase 3, long-term, open-label safety study of galcanezumab in patients with migraine. BMC Neurol. 2018;18(1):188. http://dx.doi.org/10.1186/s12883-018-1193-2

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

7. Bangs ME, Kudrow D, Wang S, et al. Safety and tolerability of monthly galcanezumab injections in patients with migraine: integrated results from migraine clinical studies. BMC Neurol. 2020;20(1):90. http://dx.doi.org/10.1186/s12883-020-01675-7

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

9. Goldman SA. Limitations and strengths of spontaneous reports data. Clin Ther. 1998;20(suppl 3):C40-C44. http://dx.doi.org/10.1016/S0149-2918(98)80007-6

Glossary

AE = adverse event

MedDRA = Medical Dictionary for Regulatory Activities

SmPC = Summary of Product Characteristics

Appendix

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)1,2

  • chronic migraine (REGAIN),3 and

  • episodic or chronic migraine that has not benefited from 2 to 4 previous migraine prevention medication categories (CONQUER).4

Galcanezumab has also been studied in a phase 3, open-label, 12-month safety study for the prevention of episodic or chronic migraine.5

The galcanezumab doses used and duration of the migraine prevention studies are summarized in Table 3.

Table 3. Summary of Study Design in the Migraine Prevention Studiesa

 

GMB Doses Studied

Study Duration

EVOLVE Studies1,2

120 mg monthlyb

or
240 mg monthly

6 months double-blind

REGAIN3

120 mg monthlyb

or
240 mg monthly

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

CONQUER4

120 mg monthlyb

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

CGAJ5

120 mg monthlyb

or
240 mg monthly

12 months open-label

Abbreviation: GMB = galcanezumab.

a With the exception of study CGAJ, all studies were randomized, double-blind, and placebo-controlled. 

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

Datum fӧr senaste ӧversyn 2020 M07 24


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