Galcanezumab

Emgality is indicated for the prophylaxis of migraine in adults who have at least 4 migraine days per month.

Treatment should be initiated by physicians experienced in the diagnosis and treatment of migraine. Posology The recommended dose is 120 mg galcanezumab injected subcutaneously once monthly, with a 240 mg loading dose as the initial dose.

Patients should be instructed to inject a missed dose as soon as possible and then resume monthly dosing. 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. Elderly (> 65 years) There is limited information in subjects aged ≥ 65 years. No dose adjustment is required as the pharmacokinetics of galcanezumab are not affected by age.

2). Paediatric population The safety and efficacy of galcanezumab in children aged 6 to 18 years have not yet been established. No data are available. There is no relevant use of galcanezumab in children below the age of 6 years for the prevention of migraine.

Method of administration Subcutaneous use. A patient may self-inject galcanezumab by following the Instructions for Use. Galcanezumab is to be injected subcutaneously in the abdomen, thigh, back of the upper arm, or in the gluteal region.

After training, patients may self-inject galcanezumab if a healthcare professional determines that it is appropriate. Comprehensive instructions for administration are given in the Package Leaflet.

Summary of the safety profile Over 2 500 patients were exposed to galcanezumab in migraine prophylaxis studies supporting the initial registration of galcanezumab. Over 1 400 patients were exposed to galcanezumab during the double-blind treatment phase of the placebo-controlled phase 3 studies.

279 patients were exposed for 12 months. 1 %). Most of the reactions were mild or moderate in severity. 5 % of patients in these studies discontinued due to adverse reactions. Tabulated list of adverse reactions Table 1. List of adverse reactions in clinical studies and post-marketing reports Frequency estimate: Very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1 000 to < 1/100), rare (≥ 1/10 000 to < 1/1 000).

System organ class Very common Common Uncommon Rare Immune system disorders Anaphylaxis Angioedema Ear and labyrinth disorders Vertigo Gastrointestinal disorders Constipation Skin and subcutaneous tissue disorders Pruritus Rash Urticaria General disorders and administration site conditions Injection site pain Injection site reactionsa a Most frequently reported terms (≥ 1 %) were: Injection site reaction, Injection site erythema, Injection site pruritus, Injection site bruising, Injection site swelling.

5 % of patients exposed to galcanezumab during the phase 3 studies discontinued the treatment due to an injection site reaction. The majority of injection site reactions were reported within 1 day and on average resolved within 5 days.

In 86 % of the patients reporting injection site pain, the reaction occurred within 1 hour of injection and resolved on average in 1 day. One percent of the patients exposed to galcanezumab during the phase 3 studies experienced severe pain at the injection site.

Urticaria While urticaria is uncommon, serious cases of urticaria have been reported in galcanezumab clinical studies. 8 % in patients receiving galcanezumab once monthly (all but one of whom had in vitro neutralizing activity). 5 % of galcanezumab-treated patients developed anti-drug antibodies, most of which were of low titre and tested positive for neutralising activity in vitro.

However, the presence of anti-drug antibodies did not affect the pharmacokinetics, efficacy, or safety of galcanezumab. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

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EMGALITY® (galcanezumab) is indicated for: • the prevention of migraine in adults who have at least 4 migraine days per month. • the reduction in the frequency of attacks throughout a cluster period in adults with episodic cluster headache with prior cluster headache periods lasting at least 6 weeks and who have had an inadequate response to, or tolerated poorly, or had contraindications to conventional preventive therapies established by Canadian practice guidelines.

For patients with episodic cluster headache, the treatment benefit should be assessed within 3 weeks after initiation of the treatment. In patients with no improvement within this time period, continuation of the treatment should be carefully considered based on individual patient basis and clinical judgement (see PART I: DOSAGE AND ADMINISTRATION and PART II: CLINICAL TRIALS).

EMGALITY should be initiated by physicians experienced in the diagnosis and treatment of migraine or episodic cluster headache. 1 Pediatrics Pediatrics (<18 years of age): No data are available to Health Canada; therefore, Health Canada has not authorized an indication for pediatric use.

2 Geriatrics Geriatrics (≥ 65 years of age): The safety and efficacy of EMGALITY has not been studied in patients aged 65 or older.

1 Dosing Considerations EMGALITY is administered subcutaneously through a single-use prefilled syringe or prefilled pen. EMGALITY is intended for patient self-administration. Administration should be performed by an individual who has been trained to administer the product (see ADMINISTRATION and INSTRUCTIONS FOR USE).

2 Recommended Dose and Dosage Adjustment Migraine The recommended dose is an initial (loading) dose of 240 mg (administered as two consecutive subcutaneous injections of 120 mg), followed by once monthly doses of 120 mg (one injection).

EMGALITY® Product Monograph Page 5 of 51 Episodic Cluster Headache The recommended dose is 300 mg once a month (administered as three consecutive subcutaneous injections of 100 mg each) at the onset of the cluster period. The dose regimen must be followed as prescribed.

The treatment benefit should be assessed within 3 weeks after initiation of the treatment. In patients with no improvement within this time period, any further decisions for continuation of the treatment during the current cluster period or initiation of the treatment for subsequent cluster periods should be carefully considered based on individual patient basis and clinical judgement (see PART II: CLINICAL TRIALS).

If further dosing is warranted, EMGALITY should not be administered more than once a month during a cluster period. EMGALITY should not be used after the end of a cluster period and during the remission time. Health Canada has not authorized an indication for pediatric use (see INDICATIONS).

3 Administration EMGALITY is for subcutaneous use only. EMGALITY may be administered by healthcare professionals, patients, and/or caregivers. Prior to use, provide proper training to patients and/or caregivers on the preparation and administration of EMGALITY prefilled syringe or prefilled pen, including aseptic technique (see INSTRUCTIONS FOR USE).

• Remove EMGALITY from the refrigerator. Prior to use, allow EMGALITY to sit at room temperature for 30 minutes protected from direct sunlight. Do not warm by using a heat source such as hot water or a microwave. • Follow aseptic injection technique every time EMGALITY is administered.

• Inspect EMGALITY visually for particles or discolouration prior to administration. Do not use if the solution is cloudy, discoloured, or contains particles (see DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING). • Do not shake the product.

• Administer EMGALITY by subcutaneous injection into areas of the abdomen, thigh, upper arm, or buttocks that are not tender, bruised, red, or indurated. • For multiple injections, you may use the same body site, but not the exact location of the previous injection.

• Do not co-administer EMGALITY with other injectable drugs at the same injection site. Migraine EMGALITY for migraine is available both as a 120 mg/mL prefilled syringe and 120 mg/mL prefilled pen. Two prefilled syringes or pens will deliver the initial 240 mg loading dose.

One prefilled syringe or pen will deliver the monthly 120 mg dose. Deliver the entire contents of the prefilled syringe or pen. Episodic Cluster Headache EMGALITY® Product Monograph Page 6 of 51 EMGALITY for episodic cluster headache is only available as a 100 mg/mL prefilled syringe.

Patients should be advised that one dose consists of three consecutive injections of 100 mg. Three prefilled syringes will deliver the 300 mg dose. Deliver the entire contents of each prefilled syringe. 4 Missed Dose Migraine Instruct patients to inject a missed dose as soon as possible.

Thereafter, resume monthly dosing. Episodic Cluster Headache The treatment benefit should be assessed within 3 weeks after initiation of the treatment. In patients with no improvement within this time period, any further decisions for continuation of the treatment during the current cluster period or initiation of the treatment for subsequent cluster periods should be carefully considered based on individual patient basis and clinical judgement (see PART II: CLINICAL TRIALS).

If patients administer a partial dose (inject only 1 or 2 of the three syringes), they should be instructed to inject the missed injection(s) as soon as possible. If further dosing is warranted and required, inject the next complete dose one month from the date of administering the missed injection(s).

1 Adverse Reaction Overview A total of 3459 patients and healthy volunteers were exposed to EMGALITY, representing more than 1807 patient years of exposure. Of these, 2129 patients were exposed to EMGALITY once monthly for at least 6 months and 750 patients were exposed for 12 months.

In the migraine and cluster headache studies, patients who had myocardial infarction, unstable angina, percutaneous coronary intervention, coronary artery bypass graft, stroke, certain ECG abnormalities or deep vein thrombosis/pulmonary embolism within 6 months of screening, or had planned cardiovascular surgery or percutaneous coronary angioplasty, and BMI ≥ 40 kg/mg2 were excluded.

In the cluster headache studies only, patients who had uncontrolled high blood pressure, characterized by systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg, and evidence of peripheral vascular disease or a diagnosis of Raynaud’s phenomenon were also excluded.

In three controlled migraine trials, 705 patients received at least one dose of EMGALITY (120 mg) once monthly. 8% of patients treated with EMGALITY discontinued double-blind treatment because of adverse events. In the two controlled cluster headache trials, 166 patients received at least one dose of EMGALITY (300 mg) once monthly.

8% treated with EMGALITY discontinued double-blind treatment because of adverse events. Adverse drug reactions (ADRs) were identified based on findings across Phase 3 efficacy and safety clinical studies in migraine and cluster headache.

The most common adverse reaction reported in ≥ 10% of patients in any study receiving galcanezumab were injection site reactions, and less frequent (≤ 2%) adverse reactions EMGALITY® Product Monograph Page 9 of 51 included constipation, vertigo, pruritus and urticaria.

Injection site reactions included multiple preferred terms, such as injection site pain, injection site erythema, injection site pruritus, injection site bruising, injection site swelling, and injection site induration. 2 Clinical Trial Adverse Reactions Because clinical trials are conducted under very specific conditions, the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.

Adverse reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates. Migraine The data described below reflect exposure to EMGALITY in 1435 patients. In the pivotal studies, the following adverse events listed in Tables 2 and 3 were observed to occur at or above 1% during the double-blind treatment phase.

2) a Denominator adjusted for female-specific event. 2) […]

EMGALITY is contraindicated in patients with known serious hypersensitivity to galcanezumab or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see DOSAGE FORMS, STRENGTHS, COMPOSITION and PACKAGING.

Emgality is indicated for the prophylaxis of migraine in adults who have at least 4 migraine days per month.

Treatment should be initiated by physicians experienced in the diagnosis and treatment of migraine. Posology The recommended dose is 120 mg galcanezumab injected subcutaneously once monthly, with a 240 mg loading dose as the initial dose.

Patients should be instructed to inject a missed dose as soon as possible and then resume monthly dosing. 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. Elderly (≥ 65 years) There is limited information in subjects aged ≥ 65 years. No dose adjustment is required as the pharmacokinetics of galcanezumab are not affected by age.

2). Paediatric population The safety and efficacy of galcanezumab in children aged 6 to 18 years have not yet been established. No data are available. 3 There is no relevant use of galcanezumab in children below the age of 6 years for the prevention of migraine.

Method of administration Subcutaneous use. A patient may self-inject galcanezumab by following the Instructions for Use. Galcanezumab is to be injected subcutaneously in the abdomen, thigh, back of the upper arm, or in the gluteal region.

After training, patients may self-inject galcanezumab if a healthcare professional determines that it is appropriate. Comprehensive instructions for administration are given in the Package Leaflet.

Summary of the safety profile Over 2 500 patients were exposed to galcanezumab in migraine prophylaxis studies supporting the initial registration of galcanezumab. Over 1 400 patients were exposed to galcanezumab during the double-blind treatment phase of the placebo-controlled phase 3 studies.

279 patients were exposed for 12 months. 1 %). Most of the reactions were mild or moderate in severity. 5 % of patients in these studies discontinued due to adverse reactions. 5 Tabulated list of adverse reactions Table 1. List of adverse reactions in clinical studies and post-marketing reports Frequency estimate: Very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1 000 to < 1/100), rare (≥ 1/10 000 to < 1/1 000).

System organ class Very common Common Uncommon Rare Immune system disorders Anaphylaxis Angioedema Ear and labyrinth disorders Vertigo Gastrointestinal disorders Constipation Skin and subcutaneous tissue disorders Pruritus Rash Urticaria General disorders and administration site conditions Injection site pain Injection site reactionsa a Most frequently reported terms (≥ 1 %) were: Injection site reaction, Injection site erythema, Injection site pruritus, Injection site bruising, Injection site swelling.

5 % of patients exposed to galcanezumab during the phase 3 studies discontinued the treatment due to an injection site reaction. The majority of injection site reactions were reported within 1 day and on average resolved within 5 days.

In 86 % of the patients reporting injection site pain, the reaction occurred within 1 hour of injection and resolved on average in 1 day. One percent of the patients exposed to galcanezumab during the phase 3 studies experienced severe pain at the injection site.

Urticaria While urticaria is uncommon, serious cases of urticaria have been reported in galcanezumab clinical studies. 8 % in patients receiving galcanezumab once monthly (all but one of whom had in vitro neutralizing activity). 5 % of galcanezumab-treated patients developed anti-drug antibodies, most of which were of low titre and tested positive for neutralising activity in vitro.

However, the presence of anti-drug antibodies did not affect the pharmacokinetics, efficacy, or safety of galcanezumab. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V. 6

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