Drug formulary listing decision – Calcitonin Gene-Related Peptide Monoclonal Antibodies in prevention of migraine


Prevention of migraine in adults who have at least four migraine days per month.

Formulary Status

The WSIB Drug Advisory Committee (DAC) recommended that injectable calcitonin gene-related peptide monoclonal antibodies (CGRP mABs) erenumab, fremanezumab and galcanezumab used in prevention of chronic/episodic migraine BE LISTED on Central Nervous System and Peripheral Nervous System Injury/Disorder (03WS) formulary, and Serious Injury (27WS) formulary with criteria:

1. Patient has confirmed diagnosis of chronic migraine (erenumab) or chronic/episodic migraine (fremanezumab/galcanezumab) defined as:

Episodic migraine: less than 15 headache days per month for more than three months, of which four days or more days per month are with migraine


2. Patient has failed two or more oral prophylactic medication trials with failure being defined as less than 30 per cent reduction in frequency of headache days when used at adequate doses (as per guidelines/monograph) and for adequate durations (i.e., ≥8 weeks);

Examples of drugs/classes to trial: beta-blockers, tricyclic antidepressants, verapamil/flunarizine, sodium valproate/divalproex sodium, topiramate, gabapentin

Note: The inability to complete an adequate medication trial (e.g., intolerable adverse effect, absolute contraindication) is considered only as one of the two failed drug trials.

3. The initial approval period shall not exceed six months.

4. Subsequent renewals should only be considered if there is clinical evidence showing ≥50% reduction in migraine days compared to baseline;

5. Two calcitonin gene-related peptide (CGRP) inhibitors should not be used in combination, and CGRP inhibitors should not be used in combination with botulinumtoxin-A products due to lack of safety and efficacy data.

The WSIB accepts the DAC recommendation.

Recommendation highlights

  • Calcitonin gene-related peptide (CGRP) is a neuropeptide associated with migraine pathophysiology and is a therapeutic target for migraine. It is involved in vasodilation, neurogenic inflammation, and nociceptive signaling associated with migraines caused by or exacerbated by work-related accidents/illnesses.
  • CGRP mABs are CGRP antagonists. They bind to and inhibits the CGRP receptor, or bind to CGRP ligand. There are four CGRP mABs on the Canadian market: erenumab, fremanezumab, galcanezumab and eptinezumab. The first three are subcutaneous self-administered injections, whereas eptinezumab is an IV infusion administered in healthcare settings.
  • The 2022 WSIB-commissioned literature review identified 17 randomized-controlled trials (RCTs), 4 post-hoc/subgroup analyses and four systematic reviews associated with CGRP mABs. All four CGRP mABs demonstrated statistically and clinically significant decrease in the frequency of migraines in comparison to placebo. Other endpoints that demonstrated positive change were the proportion of patients with 50% reduction in the number of migraines per month and the proportion of patients needing acute migraine treatment. Only one active-comparator trial was identified, erenumab vs. topiramate; erenumab demonstrated superior efficacy as a secondary endpoint.
  • Compared with standard therapeutic alternatives (e.g. propranolol, onabotulinumtoxin A, topiramate) in indirect comparisons done as part of systematic reviews, CGRP mABs are thought to have similar efficacy to existing treatments, but are better tolerated and may have improved adherence profile.
  • Galcanezumab has an additional indication for reduction of episodic cluster headache frequency based on two RCTs, but cost-effectiveness has not been established by the Canadian Agency for Drugs and Technologies in Health (CADTH) and it is not listed by any provincial and federal drug plans for this indication.
  • Common adverse events of CGRP mABs are mild to moderate injection site reactions, nausea, fatigue, upper respiratory tract infection and constipation. Adverse events of special concern are hypersensitivity reactions, cardiovascular effects, liver function abnormalities, and immunogenicity in a small number of patients
  • The three identified pharmacoeconomic evaluations of CGRP mABs in treatment of migraines were focused on erenumab, but conclusions are hard to apply to Canada as the differences in relative drug prices between different countries have a big influence on the economic analyses. The quality-adjusted year gains were similar in the trials and the conclusion reached was that the drug could be cost-effective in Canada on a limited treatment duration.
  • Galcanezumab and fremanezumab were reviewed by CADTH for the prevention of migraines and were found to be cost-effective if used with criteria. They are available in most provinces through prior authorization process, similar to the one recommended by DAC.
  • Based on the published evidence and the jurisdictional review, the DAC recommended that CGRP mABs be listed with criteria on WSIB formularies for the prevention of chronic/episodic migraine directly or indirectly caused by work-related injury/illness.

Products available in Canada

Erenumab (Aimovig®) 70 mg/1 mL, 140 mg/1 mL pre-filled syringe/autoinjector
Eptinezumab (Vyepti®) 100 mg/mL single-use vial
Fremanezumab (Ajovy®) 225 mg in 1.5 mL pre-filled syringe
Galcanezumab (Emgality®) 100 mg/1 mL, 120 mg/ 1 mL pre-filled syringe