Fremanezumab can now be used to prevent episodic migraine. Our clinical editor Mark Greener considers the exciting potential of monoclonal antibodies in this disabling condition

NICE already recommended fremanezumab to prevent chronic migraine but now suggests considering it for patients who have at least four migraine days a month.    

Over the past 20 years, calcitonin gene-related peptide (CGRP) has emerged as an important migraine mediator, which led to a new generation of preventative treatments.

Monoclonal antibodies (MAbs) targeting CGRP (fremanezumab and galcanezumab) or its receptor (erenumab) are now approved for episodic (fewer than 15 days of attacks a month) and chronic (at least 15 days) migraine.

In a pooled analysis of three randomised, double-blind phase 3 studies funded by Teva:

• 943 people received quarterly (every three months) fremanezumab
• 954 received monthly fremanezumab
• 945 received placebo.

People with episodic or chronic migraine received 675mg fremanezumab quarterly or 225mg monthly except for a 675mg first dose for chronic migraine.¹

This differs slightly from the approved regimen of 675mg quarterly or 225mg monthly (i.e. no increased initial monthly dose for chronic migraine).

Patients had responded inadequately to two to four classes of preventive treatments.¹ This also differs slightly from NICE, which recommends fremanezumab for people with migraine who do not respond to at least three preventative drugs.

“In practice, these small differences [between the analysis, NICE and the approved regimen] are unlikely to be clinically significant,” says Dr Katy Munro, a headache specialist GP working for the National Migraine Centre.

Over 12 weeks, mean reductions from baseline in the number of days each month during which patients experienced at least moderate migraine attacks were significantly greater with quarterly and monthly fremanezumab (4.5 and 4.7 days) than placebo (2.5 days).

The difference between fremanezumab and placebo emerged after a week and was sustained during the 12-week study.¹

“Some patients find that the frequency and impact of their migraine attacks lessen even within the first month. Others are slower to respond and may notice a more gradual improvement over three to six months,” Dr Munro comments.

Promising findings

Significantly more patients reported at least a 50 per cent reduction in the number of migraine attacks with quarterly and monthly fremanezumab (36 and 38 per cent) compared with placebo (19 per cent). 

A further analysis of two of the studies included in the pooled analysis reported that fremanezumab reduces migraine days, use of headache medication and headache-related disability, and was well tolerated for up to 12 months.²

The pooled analysis excluded people with “clinically significant” cardiovascular disease (CVD).¹  Migraine seems to increase CVD risk by between 29 and 70 per cent depending on the outcome.³

Indeed, the CVD risk associated with migraine appears to rise steadily with advancing age.³ Fremanezumab was well tolerated, even in the small number of people with a history of CVD.

Injection-site reactions (ISRs) were the most common adverse event. Patients inject MAbs into the abdomen, front of thighs or back of the upper arms using an auto-injector. Patients using fremanezumab also have the option of pre-filled syringes.

“Pharmacists should remind patients to store these MAbs in the fridge but allow them to come to room temperature before injecting, which may reduce ISRs,” says Dr Munro.

Fremanezumab can cause hypersensitivity reactions, including rash, pruritus and urticaria, says Teva. Most hypersensitivity reactions emerge within hours to one month after administration and are mild to moderate, but some lead to discontinuation or require corticosteroids.

Patients with a suspected hypersensitivity reaction should be referred to a GP. Patients taking MAbs can still use non-pharmacological options as well as their usual abortive [acute] medications, such as simple analgesics or triptans, says Dr Munro.

“Anti-CGRP MAbs are the first treatments to specifically target the neurochemicals implicated in triggering migraine attacks. Sadly, however, migraine is a complex, multi-factorial disorder and nothing works for every patient,” Dr Munro concludes.

“More research is needed to help us understand and treat people with this disabling condition more effectively, but having access to these exciting new medications is at least a good start.”

• Further information: nationalmigrainecentre.org.uk

1. The Journal of Headache and Pain 2021; 22:141
2. Neurology 2020; 95: e2487-e2499
3. Neurologic Clinics 2019; 37:631-649