Emgality ® (galkanezumab)

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Emgality® ▼ (galcanezumab): Underhåll av effekt vid migränförebyggande

Data från kliniska studier med galcanezumab stöder effektens varaktighet vid minskning av migränhuvudvärldagar under behandling i upp till ett år.

Detailed Information

Efficacy was sustained for up to 1 year in an open-label study in which patients with either episodic or chronic migraine (with an average baseline of 10.6 monthly MHDs) received galcanezumab 120 mg/month (with an initial loading dose of 240 mg for the first month) or galcanezumab 240 mg/month. 77.8 % of patients completed the treatment period.1

The overall mean reduction from baseline in the number of monthly MHDs averaged over the treatment phase was 5.6 days for the 120 mg dose group and 6.5 days for the 240 mg dose group. Over 72 % of patients completing the study reported a 50 % reduction in MHDs at month 12.1

In pooled data from studies EVOLVE-1 and EVOLVE-2, more than 19 % of the patients treated with galcanezumab maintained a ≥ 50 % response from Month 1 to Month 6 versus 8 % of the patients on placebo (p < 0.001).1

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

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.

The treatment benefit should be assessed within 3 months after initiation of treatment. Any further decision to continue treatment should be taken on an individual patient basis. Evaluation of the need to continue treatment is recommended regularly thereafter.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

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.2-4 

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

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

Maintenance of Effect Analysis

Maintenance of effect during the double-blind phase was evaluated based on a comparison of the percentages of galcanezumab- and placebo-treated patients with maintenance of ≥50% reduction from baseline in monthly MHDs

  • for at least 3 and 6 consecutive months for EVOLVE-1 and EVOLVE-2, and

  • 3 months for REGAIN.6

Logistic regression analyses were used for between-treatment group comparisons.6

Maintenance of Effect in Episodic Migraine Studies (EVOLVE-1 and EVOLVE-2)

The recommended dose is 120 mg galcanezumab injected subcutaneously once monthly, with a 240 mg loading dose as the initial dose.1 Please note that the results of a maintenance dose of 240 mg galcanezumab 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 1 shows the percentage of patients in the Episodic Integrated Analysis Set (EVOLVE-1 and EVOLVE-2) with ≥50% response for

  • at least 3 consecutive months until patient’s endpoint, and

  • 6 consecutive months, during the 6-month double-blind treatment phase.6,7

Compared with placebo, statistically significantly higher percentages of patients in each galcanezumab treatment group (120 mg/month and 240 mg/month) maintained ≥50% response for at least 3 or 6 consecutive months.6,7

Table 1. Maintenance of ≥50% Response Rate in Reduction in Number of Migraine Headache Days (for ≥3 Months or 6 Months) Logistic Regression Double-blind Treatment Period: EVOLVE-1 and EVOLVE-26,7

Maintenance of Response

Treatment

N

n (%)

OR

95% CI for OR

p Valuea

50% response maintained for ≥3 consecutive months until patient’s endpoint

Placebo

875

187 (21.4)

---

---

---

GMB 120 mg

436

181 (41.5)

2.6

2.1, 3.4

<.001

GMB 240 mg

428

176 (41.1)

2.6

2.0, 3.3

<.001

50% response maintained from Month 1 to Month 6

Placebo

875

70 (8.0)

--- 

---

---

GMB 120 mg

436

83 (19.0)

2.7

1.9, 3.8

<.001

GMB 240 mg

428

89 (20.8)

3.0

2.2, 4.2

<.001

Abbreviations: GMB = galcanezumab; N = total number of intent-to-treat patients with baseline and ≥1 postbaseline value; n = number of patients within each specific category; OR = Odds Ratio

a   P value from logistic regression in which X-month sustained 50% responder indicator = treatment, study, pooled region/country (study), and baseline. X is either 3 or 6, defined as follows: 3-month sustained 50% responders are defined as patients with ≥50% response for their last 3 months in the treatment phase; everyone else are non-responders, including those discontinued early within 3 months and those continued after 3 months, but did not have ≥50% response for their last 3 months; and 6-month sustained 50% responders are defined as patients with ≥50% response for all 6 months during the treatment phase. All others are non-responders, including those who discontinued early and those who completed 6-month treatment phase, but did not have ≥50% response for one or more of the 6 months.

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

Maintenance of Effect in the Chronic Migraine Study (REGAIN)

The recommended dose is 120 mg galcanezumab injected subcutaneously once monthly, with a 240 mg loading dose as the initial dose.1 Please note that the results of a maintenance dose of 240 mg galcanezumab 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.

Patients who completed the double-blind phase in the REGAIN migraine prevention clinical trial could enter a 9-month open-label treatment phase.4

In patients with chronic migraine, significantly higher percentages of patients in the galcanezumab 120 mg (17%) and 240 mg (15%) groups maintained ≥50% response for all 3 months of the double-blind treatment phase compared with placebo (6%; all p<.001).6

Sustained MHD Reduction in REGAIN Open-label Extension

At Month 3, the beginning of the open-label extension of REGAIN, all patients received a 240 mg loading dose of galcanezumab, followed by a 120 mg dose at Month 4. Starting at Month 5, patients could be dosed flexibly at the discretion of the investigator.4

Starting at Month 5, 64% of patients were switched to the 240 mg galcanezumab dose, with up to 76% of patients receiving the 240 mg dose thereafter.7

Data from the 9-month, open-label extension phase of REGAIN in patients with chronic migraine indicated that

  • reductions in MHD were sustained during this phase, and

  • percentages of patients with clinically meaningful reductions in MHDs increased from the rates observed in the double-blind period.7,8 

As shown in Figure 1, patients previously treated with placebo during double-blind treatment showed a rapid mean reduction in MHDs after their first open-label dose of galcanezumab by catching up with the double-blind treatment groups by Month 4, and then maintaining reduction over time.8

Figure 1. Mean Change From Baseline in Number of MHDs for the Double-blind and Open-label Periods of REGAIN8

 Abbreviations: GMB = galcanezumab; LS = least squares; MHD = migraine headache day; SE = standard error.

*Asterisks refer to the comparison of GMB and placebo during the double-blind phase only.

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

Maintenance of Effect in the Open-Label Safety Study (CGAJ)

The recommended dose is 120 mg galcanezumab injected subcutaneously once monthly, with a 240 mg loading dose as the initial dose.1 Please note that the results of a maintenance dose of 240 mg galcanezumab 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.

Results from CGAJ, the 12-month open-label safety study in patients with episodic or chronic migraine, further support galcanezumab’s durability of effect for up to a year.5

A decrease in the number of monthly MHDs was observed at month 1 (decreases of 4.5 and 5.2 days for the 120 mg and 240 mg doses, though both treatment groups had received 240 mg for the first month), with plateauing of effect several months later and maintenance of effect throughout 12 months (with decreases of 6.4 and 6.5 days at Month 12), see Figure 2.5,7 

In addition, in both galcanezumab treatment groups, the percentage of patients who had a ≥50%, ≥75%, and 100% reduction in MHDs tended to increase over the open-label treatment period.5

Figure 2. Mean Change From Baseline in Number of Monthly MHDs in Study CGAJ5

Abbreviations: LS = least squares; MHD = migraine headache day; SE = standard error.

*=p<.05 vs galcanezumab 120 mg.

**= p<.001 vs galcanezumab 120 mg.

Figure from: Figure 2 in Camporeale A, et al. A phase 3, long-term, open-label safety of galcanezumab in patients with migraine. BMC Neurology. 2018;18(1):188.

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

The percentage of patients in Study CGAJ who met ≥50% response at any time and subsequently maintained ≥40% response until each patient’s endpoint over 3 to 12 consecutive months, including the initial month, by treatment groups is presented in Figure 3.5

Notable percentages of patients treated with galcanezumab 120 mg or galcanezumab 240 mg maintained their response for at least 3 and up to 12 months.5

For patients treated with 120 mg and 240 mg, 49% and 52%, respectively, maintained ≥40% response for at least 6 months; and 24% and 35%, respectively, maintained this level of response for 12 months.5,7

Figure 3. Percentage of Patients Who Had ≥50% Reduction From Baseline in Migraine Headache Days and Maintained ≥40% Reduction Over 3 to 12 Consecutive Months5

Note: Denominator is the number of intent-to-treat patients with nonmissing baseline prior to randomization and with at least 1 postbaseline value for migraine headache days during the open-label treatment phase. 

Figure from: Figure 3 in Camporeale A, et al. A phase 3, long-term, open-label safety of galcanezumab in patients with migraine. BMC Neurology. 2018;18(1):188.

Note: The recommended dose is 120 mg galcanezumab injected subcutaneously once monthly, with a 240 mg loading dose as the initial dose.1 Any other dose described here is not 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.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. Camporeale A, Kudrow D, Sides R, et al. A phase 3, long-term, open-label safety study of galcanezumab in patients with migraine. BMC Neurology. 2018;18(1):188. http://dx.doi.org/10.1186/s12883-018-1193-2

6. Förderreuther S, Zhang Q, Stauffer VL, et al. Preventive effects of galcanezumab in adult patients with episodic or chronic migraine are persistent: data from the phase 3, randomized, double-blind, placebo-controlled EVOLVE-1, EVOLVE-2, and REGAIN studies. J Headache Pain. 2018;19(1):121. http://dx.doi.org/10.1186/s10194-018-0951-2

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

8. Detke HC, Li LQ, Wang S, Aurora SK. One-year treatment with galcanezumab in patients with chronic migraine: results from the open-label phase of the REGAIN study. Poster presented at 17th Biennial Migraine Trust International Symposium (MTIS); September 6-9, 2018; London, United Kingdom.

Glossary

MHD = migraine headache day

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 M01 16


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