- On 1 June 2021, galcanezumab injection (Emgality) was listed on the PBS for chronic migraine.
It is the first PBS-listed calcitonin gene-related peptide (CGRP) inhibitor.
- The listing defined chronic migraine as an average of 15 or more headaches per month, with at least 8 days of migraine, over 6 months.
The patient must have had an inadequate response, intolerance, or a contraindication to at least three prophylactic migraine medicines (propranolol, amitriptyline, pizotifen, candesartan, verapamil, nortriptyline, sodium valproate, or topiramate).
- The initial prescription must be written by the patient’s treating neurologist.
General practitioners must consult a neurologist to continue prescribing galcanezumab for their patients.
- Prescribers should be aware of flow-on changes to the PBS-listed botulinum toxin type A (Botox) for chronic migraine.
The list of prophylactic migraine medicines in the PBS Authority Required (Streamlined) criteria for botulinum toxin type A is now in line with the PBS listing for galcanezumab.
What is a headache?
There are three main types of headache.1
- Primary headaches, which may have several causes but do not develop due to an injury or illness. These include tension headaches, cluster headaches, and migraine.
- Secondary headaches, caused by an underlying health condition.
- Painful cranial neuropathies and other facial pains.
Medication overuse headache
Medication overuse can cause rebound headaches as the dose wears off, limiting its efficacy. This can cause a secondary headache disorder that is superimposed on the primary headache.2
What is a migraine?
A migraine is a moderate to severe and pulsating headache that lasts between 4 and 72 hours. It is commonly associated with nausea, vomiting, and sensitivity to light or noise. It may occur with or without aura and is more frequently one-sided (although it can be bilateral). These associated features are important in diagnosing migraine.1,3
PBAC has categorised the frequency of migraines as follows.
On 1 June 2021, galcanezumab 120 mg in 1 mL injection, 1 mL pen device (Emgality) was listed on the PBS General Schedule (Section 85) as Authority Required (Streamlined) for the preventive treatment of chronic migraine.6
There are conditions for patients to be considered for initial treatment.6
The patient must have experienced an average of 15 or more headache days per month, with at least 8 days of migraine, over at least 6 months, prior to commencement of treatment with this drug for this condition. In addition:
- the patient must have experienced an inadequate response, intolerance, or a contraindication to at least three prophylactic migraine medicines prior to commencement of treatment with this drug for this condition
- the treatment must not be in combination with botulinum toxin
- the patient must be appropriately managed by his or her practitioner for medication overuse headache, prior to initiation of treatment with this drug
- the patient must be 18 years or older.
The treatment criteria stipulate the following.6
- The patient must be treated by a neurologist.
- Prophylactic migraine medicines are propranolol, amitriptyline, pizotifen, candesartan, verapamil, nortriptyline, sodium valproate, or topiramate.
- The patient must have the number of migraine days per month documented in their medical records.
Initial treatment covers the loading (first) dose and doses at month 2 and month 3.
To be considered for continuing treatment:6
- the patient must have previously received PBS-subsidised treatment with this drug for this condition
- the patient must have achieved and maintained a 50% or greater reduction from baseline in the number of migraine days per month
- the treatment must not be in combination with botulinum toxin
- the patient must continue to be appropriately managed for medication overuse headache.
The treatment criteria stipulate that the patient must:6
- be treated by a neurologist or in consultation with a neurologist, and
- have the number of migraine days per month documented in their medical records.
Continuing treatment is treatment from month 3 onwards.
See the PBS website for complete details for each item.
What is galcanezumab?
Galcanezumab is a monoclonal antibody belonging to a group of preventive medicines that stop the activity of calcitonin gene-related peptide (CGRP), a naturally occurring substance in the body.7
Increased levels of CGRP have been associated with migraine,7 causing inflammation and pain in the nervous systems of people who have migraine episodes.8
At the time of writing, the Therapeutic Goods Administration (TGA) has approved two other CGRP inhibitors, erenumab and fremanezumab, for treating migraine in Australia, although neither is listed on the PBS.
Why was the new listing made?
Migraine can be debilitating, often causing significant lost time from everyday activities. More than 90% of people are unable to function normally during a migraine episode.9 Global burden of disease data in 2016 report migraine as the leading cause of disability among people under 50 years old.10
In Australia, first-line treatment options for migraine prevention are beta blockers, amitriptyline or topiramate. The guidelines consider valproate to be second line. Third-line options, such as botulinum toxin type A and CGRP inhibitors, are reserved for treatment under specialist supervision as long-term safety and efficacy data are lacking.11
At its November 2020 meeting, the PBAC decided that the new listing for galcanezumab offers prescribers an additional treatment option for chronic migraine for patients who have had an inadequate response, intolerance, or a contraindication to at least three other prophylactic migraine medicines.5
The submission nominated botulinum toxin type A (Botox), another PBS-listed treatment for the same patient population, as an indirect comparator.3 Galcanezumab provided a similar reduction in monthly migraine headache days and was easier to administer than botulinum toxin type A. It had acceptable cost-effectiveness based on a cost-minimisation approach compared to botulinum toxin type A.5
The PBAC recommended galcanezumab as non-interchangeable with botulinum toxin type A on an individual patient basis.5 While galcanezumab cannot be used in combination with botulinum toxin type A for PBS-subsidised treatment, it may be used sequentially before or after botulinum toxin type A for some patients.3
At its November 2020 meeting, the PBAC also considered a submission for the PBS listing of galcanezumab for the treatment of episodic migraine but did not recommend it, citing benefit uncertainty, cost-effectiveness, and no clear distinction between treatment-resistant chronic and episodic migraine in patients moving between diagnoses as the reasons.4
Evidence for galcanezumab for chronic migraine
The randomised, double-blinded, placebo-controlled REGAIN trial enrolled 1113 people with chronic migraine who had at least 15 days of headache a month, with at least 8 days of migraine, over 6 months. The trial compared two different monthly doses of galcanezumab (120 mg and 240 mg subcutaneous injections) to a placebo.12
After 3 months, treatment with galcanezumab 120 mg or 240 mg reduced the number of monthly migraine days for these patients by an average of 4.8 days (95% CI –1.9, p < 0.001) and 4.6 days (95% CI –1.9, p < 0.001) respectively, from a baseline of 19.4 days. A reduction of 2.7 days was seen for people treated with a placebo. There were no clinically meaningful differences between the lower dose of galcanezumab and placebo on any safety or tolerability outcome.12
A phase 3, open-label safety trial of 270 people with episodic (up to 14 headache days per month, with at least 4 days of migraine, over 6 months) or chronic migraine (same definition as the REGAIN study) compared two different monthly doses of galcanezumab (120 mg and 240 mg) for up to a year. The average number of monthly migraine headache days for these patients was reduced by 5.6 days (from a baseline of 9.7) and 6.5 days (from a baseline of 11.4) respectively for the two doses. Common adverse events included injection site reactions and pain, back pain, nausea, and arthralgia. The trial concluded 12 months of treatment with galcanezumab was safe and effective.13
A longer term, real-world evidence study (TRIUMPH) was launched in 2019 to compare the efficacy of galcanezumab to other preventive treatments for patients with migraine over 2 years.14
Will the changes affect current prescribing?
- Galcanezumab is the first PBS-listed CGRP inhibitor for this indication.
- It provides an additional preventive treatment option for patients with chronic migraine.5
The loading (first) dose is 240 mg (two 120 mg injections) by subcutaneous injection, followed by 120 mg (one injection) every month.7
Prescribers should evaluate treatment response after 8–12 weeks as recommended by the current Australian treatment guideline.15 Prescribers must consult with a neurologist to continue prescribing galcanezumab for their patients. Patients must have achieved and maintained a 50% or greater reduction from baseline in the number of migraine days per month to continue receiving PBS-subsidised treatment.5 Any further decision to continue treatment is taken on an individual patient basis. Evaluate the need to continue treatment regularly thereafter.7
Changes to botulinum toxin type A (Botox)
The PBAC recommended flow-on changes to botulinum toxin type A (Botox). The listing is now in line with the list of prophylactic migraine medicines in the PBS Authority Required (Streamlined) criteria for galcanezumab (Emgality). See Table 1.
Table 1. List of prophylactic migraine medicine changes and PBS criteria for botulinum toxin type A (Botox).5,16
List of prophylactic migraine medicine before 1 June 2021
List of prophylactic migraine medicine after 1 June 2021
Botulinum toxin type A 100 units injection, 1 vial
(PBS Item Code 11000Y)
Propranolol, amitriptyline, methysergide, pizotifen, cyproheptadine, or topiramate
Propranolol, amitriptyline, pizotifen, candesartan, verapamil, nortriptyline, sodium valproate, or topiramate.
What else should health professionals know?
Galcanezumab (Emgality) comes as a prefilled pen, a clear glass syringe encased in a disposable, single-use pen.7 The maximum allowable prescribed quantity of galcanezumab injection is two units, with 1 repeat of two units, for initial treatment, and one unit, with 5 repeats, for continuing treatment.5,6
Galcanezumab can cause injection site reactions such as red skin and pain. Other common side effects include vertigo (feeling of dizziness or ‘spinning’), constipation, itching and rash.
Patients may shows signs of serious hypersensitivity days after injection and symptoms may be prolonged.7
As galcanezumab is a monoclonal antibody, injecting it can trigger an immune response. This can contribute to the inactivation of its therapeutic effects and potentially induce adverse effects. In a long-term study, 12.4% of patients developed antidrug antibodies after injecting the recommended monthly dose of galcanezumab 120 mg for 12 months. It had no noticeable effect on treatment efficacy.13
No studies have assessed galcanezumab in combination with other medicines targeting CGRP or the CGRP receptor. The safety of such combinations is unknown.
It is contraindicated for patients with known serious hypersensitivity to galcanezumab or to any of the excipients.7
What should patients and carers know?
How is galcanezumab given?
Galcanezumab (Emgality) is given as an injection under the skin (subcutaneous injection) every month. It should be injected at the same date each month. You and your doctor or nurse should decide if you can give the injection yourself (self-injection) after the initial doses or have a carer give it to you after proper injection training.
Before you or your carer start giving injections, it is important to have a doctor, pharmacist, or nurse show you what is involved, and make sure you understand what to do. Do not start this medicine without proper injection training.
Instructions for injection are also included in the package insert to help you remember what to do. Sites for injection include the abdomen and thigh for self-injection, or in addition the back of the upper arm and buttocks if another person is giving the injection.
Always inspect the syringe before injection. Do not use the medicine if it is cloudy, or there are any visible particles in the fluid.7
Galcanezumab (Emgality) helps to control your condition but does not cure it. It is important to keep taking it even if you feel well.
In the case of a missed dose, inject the missed dose as soon as possible and then resume monthly dosing from the date of the last dose.7
Shelf life and storage
Galcanezumab (Emgality) has a shelf life of 2 years when stored in a fridge (2 °C to 8 °C) away from light until use.
It can be left out of the fridge for up to 7 days at temperatures up to 30 °C. Dispose of it if the storage conditions exceed this. Once stored out of refrigeration, do not place it back in the fridge.7
Dispose of any unused medicine or waste material by taking it to your local pharmacy.7
Side effects of galcanezumab can include:
- injection site reactions such as red skin and pain (changing injection sites may help)
- vertigo (a feeling of dizziness or ‘spinning’)
If you experience signs of allergy, consult with your prescriber as soon as possible.7
- Neurology Expert Group. Therapeutic Guidelines: Classifying headache and facial pain. West Melbourne: Therapeutic Guidelines Ltd, 2017 (accessed 1 June 2021).
- Neurology Expert Group. Therapeutic Guidelines: Medication overuse headache. West Melbourne: Therapeutic Guidelines Ltd, 2017 (accessed 3 June 2021).
- Pharmaceutical Benefits Advisory Committee. PBAC Public Summary Document: galcanezumab injection (Emgality) July 2019 PBAC Meeting. Canberra: Australian Government Department of Health, 2019 (accessed 25 May 2021).
- Pharmaceutical Benefits Advisory Committee. PBAC Public Summary Document: galcanezumab (episodic migraine) injection (Emgality) November 2020 PBAC Meeting. Canberra: Australian Government Department of Health, 2020 (accessed 25 May 2021).
- Pharmaceutical Benefits Advisory Committee. PBAC Public Summary Document: galcanezumab (chronic migraine) injection (Emgality) November 2020 PBAC Meeting. Canberra: Australian Government Department of Health, 2020 (accessed 25 May 2021).
- Pharmaceutical Benefits Scheme. PBS Schedule: Summary of Changes (June 2021). Canberra: Australian Government Department of Health, 2021 (accessed 1 June 2021).
- Australian Register of Therapeutic Goods. Australian product information - Emgality (galcanezumab) prefilled pen and prefilled syringe. Canberra: ARTG, 2019 (accessed 25 May 2021).
- Iyengar S, Johnson KW, Ossipov MH, et al. CGRP and the trigeminal system in migraine. Headache 2019;59:659-81.
- Lipton RB, Bigal ME, Diamond M, et al. Migraine prevalence, disease burden, and the need for preventive therapy. Neurology 2007;68:343-9.
- Steiner TJ, Stovner LJ, Vos T, et al. Migraine is first cause of disability in under 50s: will health politicians now take notice? J Headache Pain 2018;19:17.
- Australian Medicines Handbook. Prevention of migraine. Adelaide: AMH Pty Ltd, 2021 (accessed 25 May 2021).
- Detke HC, Goadsby PJ, Wang S, et al. Galcanezumab in chronic migraine: The randomized, double-blind, placebo-controlled REGAIN study. Neurology 2018;91:e2211-e21.
- 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;18:188.
- Eli Lilly and Company. News release: Lilly Announces the Launch of TRIUMPH, the First, Long-Term, Real-World Evidence Study of Emgality (galcanezumab-gnlm). Indianapolis: Eli Lilly and Company, 2019 (accessed 25 May 2021).
- Neurology Expert Group. Therapeutic Guidelines: Migraine. West Melbourne: Therapeutic Guidelines Ltd, 2017 (accessed 25 May 2021).
- Pharmaceutical Benefits Scheme. Botulinum toxin type A. Canberra: Australian Government Department of Health, 2021 (accessed 25 May 2021).