Consumer medicine information

Emgality

Galcanezumab

BRAND INFORMATION

Brand name

Emgality

Active ingredient

Galcanezumab

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Emgality.

What is in this leaflet

This leaflet answers some common questions about EMGALITY. It does not contain all the available information. It should not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking EMGALITY against the benefits they expect it will have for you.

If you have any concerns about taking this medicine, talk to your doctor or pharmacist.

Keep this leaflet with the medicine. You may need to read it again.

What EMGALITY is used for

EMGALITY is used to prevent migraine in adult patients.

Migraine is a disease affecting the nervous system where patients suffer with repeated headaches, often only affecting one side of the head. The headaches are commonly associated with feeling nauseous, or actually vomiting, and patients can also be very sensitive to light and sound.

The active ingredient in EMGALITY is galcanezumab. Galcanezumab belongs to a group of preventative medicines that stop the activity of a naturally occurring substance in the body called calcitonin-gene-related peptide (CGRP). Increased levels of CGRP have been associated with migraine.

EMGALITY has been shown to improve quality of life by significantly reducing the frequency of migraine headache, with an onset of effect as early as one week after starting treatment.

Ask your doctor if you have any questions about why EMGALITY has been prescribed for you. Your doctor may have prescribed it for another reason.

EMGALITY is available only with a doctor's prescription.

EMGALITY could have a minor effect on your ability to drive and use machines. Some patients have had vertigo whilst using EMGALITY.

EMGALITY has not been studied in patients under 18 years of age.

Before you take EMGALITY

When you must not take it

Do not take EMGALITY if you have an allergy to:

  • Galcanezumab
  • Any of the ingredients listed at the end of this leaflet.

Some of the symptoms of an allergic reaction may include:

  • shortness of breath
  • wheezing or difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives on the skin.

Do not give this medicine to children and adolescents under 18 years of age. EMGALITY is not recommended for children and adolescents under 18 years of age because it has not been studied in this age group.

Do not take this medicine after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering. If it has expired or is damaged, return it to your pharmacist for disposal.

If you are not sure whether you should start taking this medicine, talk to your doctor.

Before you start to take it

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you are pregnant or plan to become pregnant or are breast-feeding. If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine. It is preferable to avoid the use of EMGALITY in pregnancy, as the effects of this medicine in pregnant women are not known.

Your doctor will advise the most appropriate contraceptive method for you to take while using EMGALITY.

If you are breast-feeding or are planning to breast-feed, talk to your doctor before using this medicine. You and your doctor should decide if you should breast-feed and use EMGALITY.

If you have not told your doctor about any of the above, tell him/ her before you start taking EMGALITY.

Taking other medicines

Tell your doctor or pharmacist if you are taking any other medicines, including any that you get without a prescription from your pharmacy, supermarket or health food shop. Some medicines and EMGALITY may interfere with each other.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking this medicine.

How to take EMGALITY

Follow all directions given to you by your doctor or pharmacist carefully. They may differ from the information contained in this leaflet.

If you do not understand the instructions on the box, ask your doctor or pharmacist for help.

EMGALITY is given by injection under your skin (subcutaneous injection). You and your doctor or nurse should decide if you should inject EMGALITY yourself.

It is important not to try to inject yourself until you have been trained by your doctor, pharmacist or nurse. A caregiver may also give you your EMGALITY injection after proper training.

Comprehensive instructions for administration are given in the Instructions For Use in the package insert.

How much to take

Each pen and syringe contains one dose of EMGALITY (120 mg). Each pen or syringe delivers only one dose.

  • The first dose is 240 mg (two 120 mg injections) by subcutaneous injection.
  • After the first dose, you will use a 120 mg dose (one injection) every month.

How to take it

The pen and syringe must not be shaken.

Read the "Instructions for Use" for the pen or syringe carefully before using EMGALITY.

When to take it

Take your medicine at about the same time each month.

Taking it at the same time each month will have the best effect. It will also help you remember when to take it.

How long to take it

Your doctor will decide how long you should use EMGALITY.

This medicine helps to control your condition, but does not cure it. It is important to keep taking your medicine even if you feel well.

If you forget to take it

Do not take a double dose to make up for the forgotten injection when you next inject.

If you have forgotten to inject a dose of EMGALITY, inject the missed dose as soon as possible and then resume monthly dosing.

If you are not sure what to do, ask your doctor or pharmacist.

If you have trouble remembering to take your medicine, ask your pharmacist for some hints.

If you take too much (overdose)

If, after the initial dose of 240 mg, you have injected twice in a single monthly period, then you should inform your doctor.

While you are using EMGALITY

Things you must do

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are taking EMGALITY.

If you become pregnant while taking this medicine, tell your doctor immediately.

Keep all of your doctor’s appointments so that your progress can be checked.

Things you must not do

Do not take EMGALITY to treat any other complaints unless your doctor tells you to.

Do not give your medicine to anyone else, even if they have the same condition as you.

Do not stop taking your medicine, or change the dosage, without checking with your doctor.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking EMGALITY.

This medicine helps most people with migraine, but it may have unwanted side effects in a few people. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

Do not be alarmed by the following list of side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor or pharmacist if you notice any of the following and they worry you:

  • Injection site reactions e.g. red skin, pain.
  • Vertigo (a feeling of dizziness or 'spinning').
  • Constipation.
  • Itching.
  • Rash

The above list includes the more common side effects of your medicine. They are usually mild and short-lived.

Tell your doctor as soon as possible if you notice:

  • Sudden signs of allergy such as rash, itching, hives on the skin, swelling of the face, lips, tongue or other parts of the body, shortness of breath, wheezing or trouble breathing
  • swelling of the face, lips, mouth, tongue or throat which may be rapid and may cause difficulty in swallowing or breathing.

The above list includes serious side effects that may require medical attention. Serious side effects are rare.

Although the allergic reactions usually seen with EMGALITY are mild to moderate (such as rash or itching), it is possible that more serious reactions could occur, so it is important for you to stop using EMGALITY and tell your doctor if you think that you have had an allergic reaction.

Tell your doctor or pharmacist if you notice anything that is making you feel unwell.

Other side effects not listed above may also occur in some people.

After taking EMGALITY

Storage

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the label and on the carton after 'EXP'. The expiry date refers to the last day of that month.

Store in a refrigerator (2°C to 8°C). Do not freeze.

Store in original packaging in order to protect from light.

EMGALITY can be left out of the fridge for up to 7 days at a temperature not above 30°C. If these conditions are exceeded, then EMGALITY must be thrown away. Once EMGALITY has been stored out of refrigeration, do not place it back in the refrigerator.

Do not use this medicine if you notice that the pen or syringe is damaged, or that the medicine is cloudy or has particles in it.

This medicine is for single use only.

Disposal

If your doctor tells you to stop taking this medicine or the expiry date has passed, ask your pharmacist what to do with any medicine that is left over.

Do not throw away any medicines via wastewater or household waste. Ask your doctor, nurse or pharmacist how to throw away medicines you no longer use. This will help protect the environment.

Product Description

What it looks like

Prefilled Pen:

EMGALITY is a solution in a clear glass syringe. Its colour may vary from colourless to slightly yellow. The syringe is encased in a disposable, single-dose pen.

Prefilled pens may be available in pack sizes of 1, 2, or 3.

Prefilled Syringe:

EMGALITY is a solution in a clear glass syringe. Its colour may vary from colourless to slightly yellow.

Prefilled syringes may be available in pack sizes of 1, 2 or 3.

Note: all presentations or pack sizes may not be available.

Ingredients

EMGALITY contains 120 mg of galcanezumab as the active ingredient.

  • Histidine
  • Histidine hydrochloride monohydrate
  • Polysorbate 80
  • Sodium chloride
  • Water for injections

This medicine does not contain lactose, sucrose, gluten, tartrazine or any other azo dye.

Supplier

EMGALITY is supplied in Australia by:

Eli Lilly Australia Pty Ltd
Level 9, 60 Margaret Street
Sydney NSW 2000
AUSTRALIA

®= Registered Trademark

If you have any questions about EMGALITY, contact Eli Lilly at 1800 454 559 (Australia) or your healthcare professional for assistance.

Australian Registration Numbers

EMGALITY 120 mg/mL prefilled pen – AUST R 302146

EMGALITY 120 mg/mL prefilled syringe – AUST R 302145

Further Information

© Copyright

This leaflet was prepared in March 2023

vA2.0

Published by MIMS May 2023

BRAND INFORMATION

Brand name

Emgality

Active ingredient

Galcanezumab

Schedule

S4

 

1 Name of Medicine

Galcanezumab.

2 Qualitative and Quantitative Composition

Each prefilled pen (autoinjector) or prefilled syringe contains 120 mg of galcanezumab in 1 mL.
Emgality solution is sterile and preservative-free.
Galcanezumab is a humanised monoclonal antibody (IgG4) produced in Chinese Hamster Ovary (CHO) cells by recombinant DNA technology. It is composed of two identical immunoglobulin kappa light chains and two identical immunoglobulin gamma heavy chains (molecular weight = 144,084 Da non-glycosylated, disulfide linked).
Emgality is administered as a subcutaneous injection.

Excipient with known effect.

Each 1 mL of product contains approximately 3.5 mg sodium.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Solution for injection in pre-filled pen (autoinjector).
Solution for injection in pre-filled syringe.
The solution is clear and colourless to slightly yellow.

4 Clinical Particulars

4.1 Therapeutic Indications

Emgality is indicated for the prophylaxis of migraine in adults.

4.2 Dose and Method of Administration

Dosage.

Emgality should be initiated by physicians experienced in the diagnosis and treatment of migraine.
The recommended dose is 120 mg galcanezumab injected subcutaneously once monthly, with a 240 mg loading dose as the initial dose.
Treatment response should be evaluated by the prescriber after 8-12 weeks as recommended by the current Australian treatment guideline. 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.
Instruct patients to inject a missed dose as soon as possible. Thereafter, resume monthly dosing.

Method of administration.

Emgality is for subcutaneous administration.
A patient may self-inject Emgality by following the instructions for use.
Sites for injection include the abdomen, thigh, back of the upper arm and buttocks.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use Emgality if it is cloudy, or there are visible particles.
Emgality is for single use in one patient only. Discard any residue.
Comprehensive instructions for administration are given in the Instructions For Use in the package insert.

4.3 Contraindications

Emgality is contraindicated in patients with known serious hypersensitivity to galcanezumab or to any of the excipients.

4.4 Special Warnings and Precautions for Use

Serious hypersensitivity.

Serious hypersensitivity reactions, including cases of anaphylaxis, angioedema and urticaria have been reported. If a serious hypersensitivity reaction occurs, discontinue galcanezumab immediately and initiate appropriate therapy. Serious hypersensitivity reactions could occur days after administration and may be prolonged.

Use in the elderly.

Dose adjustments for patients aged 65 years and older are not recommended due to insufficient data to determine whether they respond differently from younger subjects.

Paediatric use.

No data available.

Effects on laboratory tests.

Data available but there is no evidence of clinically meaningful effect on any particular test.

4.5 Interactions with Other Medicines and Other Forms of Interactions

No studies have assessed galcanezumab in combination with other agents targeting CGRP or the CGRP receptor, and it is not known whether such combinations are safe.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data are available of the effect of Emgality on human fertility. No effects on fertility parameters such as reproductive organs, oestrous cycle, sperm analysis, or mating and fertility were observed in male and female rats that were administered galcanezumab at subcutaneous doses of 250 mg/kg every 3 to 7 days that are 8 to 38 times the systemic exposure [based on AUC] in patients given an initial loading dose of 240 mg followed by the recommended dose of 120 mg monthly.
(Category B1)
There are insufficient human data to establish the safety of Emgality during pregnancy.
In embryofetal development toxicity studies in pregnant rabbits and rats, galcanezumab was administered subcutaneously every 3 to 7 days throughout pregnancy at doses up to 100 to 250 mg/kg, respectively (approximately 64 and 38 times the systemic exposure [AUC] in patients, respectively). Galcanezumab did not cause any maternal toxicity or embryofetal harm. In a separate rat pre- and postnatal development study, galcanezumab given subcutaneously at doses up to 250 mg/kg once every 3 days did not cause any adverse developmental effects on neonates (approximately 34 times the exposure in patients, based on AUC).
Galcanezumab, like other IgG antibodies, was shown in rats and rabbits to cross the placental barrier. It is not known whether Emgality can cause fetal harm when administered to pregnant women. Emgality should be used in pregnancy only if the potential benefit justifies the potential risk to the mother or fetus.
 There are no data on the presence of galcanezumab in human milk, the effects on the breastfed infant, or the effects on milk production. Human IgG is known to be excreted in breast milk; therefore, galcanezumab may be transmitted from the mother to the breastfed infant. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Emgality and any potential adverse effects on the breastfed infant.

4.7 Effects on Ability to Drive and Use Machines

There are no known effects on the ability to drive or use machines associated with the use of Emgality. Vertigo may occur following the administration of galcanezumab (see Section 4.8).

4.8 Adverse Effects (Undesirable Effects)

Over 2500 patients were exposed to galcanezumab in clinical studies in migraine prophylaxis. Over 1400 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.
The reported adverse drug reactions for 120 mg and 240 mg were injection site pain (10.1%/11.6%), injection site reactions (9.9%/14.5%), vertigo (0.7%/1.2%), constipation (1.0%/1.5%), pruritus (0.7%/1.2%) and urticaria (0.3%/0.1%). Most of the reactions were mild or moderate in severity. Less than 2.5% of patients in these studies discontinued due to adverse events. See Table 1.
While the data are limited for a comprehensive assessment of withdrawal and rebound effects, there is no evidence of such an effect based on review of migraine adverse events.
Review of adverse events open-label extension/active treatment period combined over a minimum period of 1 year did not reveal any signals or trends that would suggest a potential safety concern with long-term exposure to Emgality.

Injection site reactions.

Injection site pain was the most frequently (≥ 10%) reported event. Other adverse reactions at the injection site reported ≥ 1% were: Injection site reaction, Injection site erythema, Injection site pruritus, Injection site bruising, Injection site swelling. The majority of events related to the injection site were mild to moderate and less than 0.5% 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 event 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.

Immunogenicity.

In the clinical studies, the incidence of anti-drug antibody development during the double blind treatment phase was 4.8% in patients receiving galcanezumab once monthly (all but one of whom had in vitro neutralising activity). With 12 months of treatment, up to 12.5% of Emgality-treated patients developed treatment-emergent 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.

Postmarketing data.

The following adverse effects (undesirable effects) are based on postmarketing spontaneous reports:

Immune system disorders.

Anaphylaxis: rare (≥ 0.01% - < 0.1%).
Angioedema: rare (≥ 0.01% - < 0.1%).

Skin and subcutaneous tissue disorders.

Rash: common (≥ 1% - < 10%).

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration 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 at http://www.tga.gov.au/reporting-problems.

4.9 Overdose

Doses up to 600 mg have been administered subcutaneously to humans without dose-limiting toxicity. In case of an overdose, it is recommended that the patient be monitored for any signs or symptoms of adverse reactions and appropriate symptomatic treatment be instituted immediately.
For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Calcitonin gene-related peptide (CGRP) is a key mediator of capsaicin-induced dermal blood flow. Single doses of galcanezumab (75, 200, or 600 mg) resulted in attenuation of capsaicin-induced dermal blood flow by Day 3. Galcanezumab at 150 mg every 2 weeks for 6 weeks (4 total doses) resulted in an inhibition of capsaicin-induced dermal blood flow for at least 134 days after the last dose was given.

Mechanism of action.

Galcanezumab is a humanised IgG4 monoclonal antibody that binds CGRP and prevents its biological activity without blocking the CGRP receptor. Elevated blood concentrations of CGRP have been associated with migraine. In addition, CGRP infusions can induce migraine-like attacks in some individuals with a history of migraine.
Galcanezumab targets CGRP and binds with high affinity (KD = 31 picoM) and high specificity (> 10,000-fold versus related peptides adrenomedullin, amylin, calcitonin and intermedin).

Clinical trials.

Clinical efficacy and safety. The efficacy and safety of galcanezumab has been studied in 3 phase 3, randomized, placebo-controlled, double blind studies in adult patients (N = 2886). The 2 episodic migraine studies (EVOLVE-1 and EVOLVE-2) enrolled patients who met International Classification of Headache Disorders (ICHD) criteria for a diagnosis of migraine with or without aura with 4-14 migraine headache days per month. The chronic migraine study (REGAIN) enrolled patients who met ICHD criteria for chronic migraine with ≥ 15 headache days per month, of which at least 8 had the features of migraine. Patients with recent acute cardiovascular events (including MI, unstable angina, CABG, stroke, DVT) and/or those deemed to be at serious cardiovascular risk were excluded from the galcanezumab clinical trials. Patients > 65 years of age were also excluded.
Patients received placebo, galcanezumab 120 mg/month (with an initial loading dose of 240 mg for the first month) or galcanezumab 240 mg/month and were allowed to use medication for the acute treatment of migraine. 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. Approximately one-third of patients across the studies had at least 1 prior failure on a migraine prophylactic treatment for efficacy reasons and approximately 16% of patients across the studies had at least 2 prior failures on a prophylactic treatment for efficacy reasons.
In all 3 studies, the overall mean change from baseline in number of monthly Migraine Headache Days (MHDs) was the primary efficacy measure. Response rate is the mean percentage of patients meeting a defined threshold in the reduction of the number of monthly MHDs (≥ 50%, ≥ 75% and 100%) across the double blind treatment period. The impact of migraine on functioning was assessed by the Role Function-Restrictive domain of the Migraine-Specific Quality of Life Questionnaire (MSQ) version 2.1, and by the Migraine Disability Assessment (MIDAS) Questionnaire. The MSQ measures impact of migraine on work or daily activities, relationships with family and friends, leisure time, productivity, concentration, energy, and tiredness. Scoring ranges from 0 to 100, with higher scores indicating less impairment, that is, patients experience fewer restrictions on the performance of day-to-day activities. For the MIDAS, higher scores indicate more disability. The baseline scores of the MIDAS reflected severe migraine related disability of patients in EVOLVE-1 and EVOLVE-2 (mean of 33.1) and a very severely disabled population (mean of 67.2) in REGAIN.

Episodic migraine.

Studies EVOLVE-1 and EVOLVE-2 had a 6 month, double blind, placebo controlled treatment period. Completion rate of the double blind treatment phase for patients who received galcanezumab ranged from 82.8% to 87.7%.
Both galcanezumab 120 mg and 240 mg treatment groups demonstrated statistically significant and clinically meaningful improvements from baseline compared to placebo on mean change in MHD (see Table 2). Patients treated with galcanezumab had greater response rates and greater reductions in the number of monthly MHDs for which acute medication was taken compared with placebo-treated patients. Galcanezumab-treated patients had a greater improvement in functioning (as measured by the MSQ Role Function-Restrictive domain score) compared with placebo-treated patients, beginning at month 1. More patients treated with galcanezumab achieved clinically significant levels of improvement in functioning (responder rate based on MSQ Role Function Restrictive domain) compared with those treated with placebo. Galcanezumab was associated with a statistically significant reduction in disability over placebo.
Compared with placebo-treated patients, patients treated with galcanezumab 120 mg or 240 mg had significantly greater mean decreases from baseline in the number of monthly MHDs at month 1 and at all subsequent months up to month 6 (see Figure 1). Additionally, in month 1, patients treated with galcanezumab (loading dose of 240 mg) demonstrated significantly fewer weekly MHDs compared with placebo-treated patients, at week 1 and each subsequent week.
In pooled data from studies EVOLVE-1 and EVOLVE-2, in patients who failed one or more prophylactic treatments for efficacy reasons, the treatment difference for the reduction of mean monthly MHDs observed between galcanezumab 120 mg and placebo was -2.69 days (p < 0.001) and between galcanezumab 240 mg and placebo -2.78 days (p < 0.001). In patients failing two or more prophylactic treatments, the treatment difference was -2.64 days (p < 0.001) between 120 mg and placebo and -3.04 days (p < 0.001) between 240 mg and placebo.

Chronic migraine.

Study REGAIN had a 3 month, double blind, placebo-controlled treatment period followed by a 9 month open-label extension. Approximately 15% of the patients continued concurrent treatment with topiramate or propranolol as allowed by the protocol for prophylaxis of migraine. Completion rate of the double blind treatment phase for patients who received galcanezumab was 95.3%.
Both galcanezumab 120 mg and 240 mg treatment groups demonstrated statistically significant and clinically meaningful improvements from baseline compared to placebo on mean change in MHD (see Table 3). Patients treated with galcanezumab had greater response rates and greater reductions in the number of monthly MHDs for which acute medication was taken compared with placebo-treated patients. Galcanezumab-treated patients had a greater improvement in functioning (as measured by the MSQ Role Function-Restrictive domain score) compared with placebo-treated patients, beginning at month 1. More patients treated with galcanezumab achieved clinically significant levels of improvement in functioning (responder rate based on MSQ Role Function Restrictive domain) compared with those treated with placebo. The 120 mg dose was associated with a statistically significant reduction in disability over placebo.
Compared with placebo-treated patients, patients treated with galcanezumab 120 mg or 240 mg had significantly greater mean decreases from baseline in the number of monthly MHDs at the first month and at all subsequent months up to month 3 (see Figure 2). Additionally, in month 1, patients treated with galcanezumab (loading dose of 240 mg) demonstrated significantly fewer weekly MHDs compared with placebo-treated patients, at week 1 and each subsequent week.
In patients who failed one or more prophylactic treatments for efficacy reasons, the treatment difference for the reduction of mean monthly MHDs observed between galcanezumab 120 mg and placebo was -3.54 days (p < 0.001) and between galcanezumab 240 mg and placebo -1.37 days (p < 0.05). In patients failing two or more prophylactic treatments, the treatment difference was -4.48 days (p < 0.001) between 120 mg and placebo and -1.86 days (p < 0.01) between 240 mg and placebo.
Sixty-four percent of the patients had acute headache medication overuse at baseline. In these patients, the treatment difference observed between galcanezumab 120 mg and placebo and between galcanezumab 240 mg and placebo for the reduction of MHDs in these patients was respectively -2.53 days (p < 0.001) and -2.26 days (p < 0.001).

Long term efficacy.

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. 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. 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).

5.2 Pharmacokinetic Properties

Absorption.

Based on a population pharmacokinetic (PK) analysis, following a loading dose of 240 mg the maximum serum concentration (Cmax) of galcanezumab was approximately 30 microgram/mL (27% coefficient of variation [CV]) and the time to Cmax was 5 days postdose.
Monthly doses of 120 mg or 240 mg achieved a steady-state Cmax (Cmax,ss) of approximately 28 microgram/mL (35% CV) or 54 microgram/mL (31% CV), respectively. The galcanezumab Cmax,ss at monthly doses of 120 mg is achieved after the 240 mg loading dose.
Injection site location did not significantly influence the absorption of galcanezumab.

Distribution.

Based on a population PK analysis, the apparent volume of distribution (V/F) of galcanezumab was 7.3 L.

Metabolism.

As a humanised IgG4 monoclonal antibody, galcanezumab is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG.

Excretion.

Based on a population PK analysis, the apparent clearance (CL/F) of galcanezumab was approximately 0.008 L/h and the half-life of galcanezumab was 27 days.

Dose linearity.

Galcanezumab exposure increases proportionally with dose.
Based on a population PK analysis that included doses ranging from 5 - 300 mg, the rate of absorption, CL/F and V/F was independent of dose.

Special populations.

Age, sex, weight, race, ethnicity.

No dose adjustment is needed on the basis of age, sex, weight, race or ethnicity as there was no clinically meaningful effect of these factors on the CL/F or V/F of galcanezumab.

Renal or hepatic impairment.

Specific clinical pharmacology studies to evaluate the effects of renal impairment and hepatic impairment on the PK of galcanezumab were not conducted. Renal elimination of IgG monoclonal antibodies is low. Similarly, IgG monoclonal antibodies are mainly eliminated via intracellular catabolism and hepatic impairment is not expected to influence clearance of galcanezumab. Based on a population PK analysis, bilirubin concentration or creatinine clearance did not significantly influence the CL/F of galcanezumab.

5.3 Preclinical Safety Data

Genotoxicity.

No genotoxicity studies have been conducted. As a monoclonal antibody, galcanezumab is not expected to interact with DNA or other chromosomal material.

Carcinogenicity.

Nonclinical studies have not been conducted to evaluate the carcinogenic potential of galcanezumab. There is no nonclinical evidence to suggest that chronic treatment with galcanezumab would increase the risk of carcinogenesis based on data from pharmacology and chronic toxicology studies with galcanezumab as well as an assessment of the literature regarding CGRP.

6 Pharmaceutical Particulars

6.1 List of Excipients

Histidine, histidine hydrochloride monohydrate, polysorbate 80, sodium chloride, water for injections.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

The shelf life is 2 years when stored at 2°C to 8°C.
May be stored unrefrigerated for up to 7 days when stored at temperatures up to 30°C. If these conditions are exceeded, Emgality must be discarded. Once Emgality has been stored out of refrigeration, do not place it back in the refrigerator.

6.4 Special Precautions for Storage

Store refrigerated at 2°C to 8°C.
Protect Emgality from light until use.
Do not freeze.
Do not shake.

6.5 Nature and Contents of Container

Emgality is available in a single-dose prefilled pen (autoinjector). Pack sizes of 1, 2, 3.
Emgality is available in a single-dose prefilled syringe. Pack sizes of 1, 2, 3.
Note: not all presentations or pack sizes may be available.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Chemical structure.


CAS number.

The CAS number for galcanezumab is 1578199-75-3.

7 Medicine Schedule (Poisons Standard)

Schedule 4 - Prescription Only Medicine.

Summary Table of Changes