AJOVY (frémanezumab)

Key points

Approved for reimbursement only for adult patients suffering from severe migraine with at least 8 migraine days per month, with previous failure to at least two prophylactic treatments and without cardiovascular disease (patients who have had clinically significant cardiovascular disease or vascular ischemia, or thromboembolic event).

Clinical benefit now substantial (previously it was moderate) in this indication.

Therapeutic improvement?

No therapeutic improvement?

Role in therapeutic strategy?

The treatment of migraine is based on treating acute episodes, and where applicable, setting up of a basic prophylactic treatment with a view to reducing the frequency of acute episodes.

The substances used for treating acute episodes are non-migraine-specific treatments (analgesics and non-steroidal anti-inflammatory drugs), and migraine-specific treatments (primarily triptans and ergot derivatives).

The choice of prophylactic treatment is based on the patient’s adverse effects, contraindications, interactions, and associated conditions, if applicable. The substances authorised for migraine prophylaxis and used as a first-line treatment are beta blockers (metoprolol and propranolol) and topiramate. Amitriptyline (LAROXYL film-coated tablet and oral solution proprietary medicinal products) also has an indication in the basic treatment of migraine in adults. This indication has not been assessed by the Committee to date. The recent 2021 guidelines issued by the French Society for the Study of Migraine and Headache rank amitriptyline as the first-line treatment of episodic migraine where beta blocker treatment is inappropriate.

If these treatments fail, the alternative prophylactic migraine treatments are as follows:

• oral treatments authorised for basic treatment of migraine (pizotifen, oxetorone, flunarizine), but only used as an alternative treatment due to their safety profile in particular,
• anti-CGRP antibodies (erenumab [AIMOVIG], galcanezumab [EMGALITY] and fremanezumab [AJOVY]) providing alternatives for patients suffering from severe migraine with at least 8 migraine days per month, with previous failure to at least two prophylactic treatments and without cardiovascular disease,
• the proprietary medicinal product BOTOX (botulinum toxin A) for which an extension of indication was recently granted specifically for chronic migraine (presence of headache at least 15 days per month, including at least 8 days of migraine per month), and was recently assessed by the Committee (Transparency Committee opinion of 17 November 2021); this proprietary medicinal product provides a medication option for the chronic migraine prophylaxis in patients who have failed to respond to or are intolerant to other oral treatments for migraine prophylaxis.

Other substances are also used off-label for basic migraine treatment with a lower level of evidence of efficacy (high to moderate): antiepileptics (valproate and sodium divalproate), beta blockers (atenolol, nebivolol, timolol), candesartan.

Role of AJOVY (fremanezumab) in the therapeutic strategy within the scope of indications covered by this reassessment:

Considering:

• the efficacy data or fremanezumab versus placebo, based on the previously assessed FOCUS study, among patients failing to respond to 2 to 4 prophylactic treatments and mostly experiencing at least 8 days of migraine per month, and the medical need of these patients, particularly resulting in the recommendation of reimbursement in this context,
• the new efficacy data based on intermediate analyses of observational studies and their limitations, particularly in terms of transposability (proportion of missing data, lack of information on concomitant treatments received, etc.),
• the uncertainty as to the cardiac safety observed in patients from the different studies while patients with severe cardiovascular disease were excluded by the protocols; this uncertainty remains in spite of new safety data based on pharmacovigilance follow-up,

the Committee deems that AJOVY (fremanezumab) remains a medication option for adult patients suffering from severe migraine with at least 8 migraine days per month, with previous failure to at least two prophylactic treatments and without cardiovascular disease (patients who have had clinically significant cardiovascular disease or vascular ischemia, or thromboembolic event).

The new data are not liable to modify the role of AJOVY (fremanezumab) in the therapeutic strategy previously established by the Committee in its inclusion opinion of 16 September 2020.

The Committee stresses that, in accordance with the SPC, the benefit of the treatment must be assessed within 3 months following the start of treatment with a decision whether to continue treatment made on a case-by-case basis, and regular assessment of the clinical response recommended thereafter.

Efficacy data with more than one year of follow-up remain limited. Based on expert opinion, continued treatment beyond one year requires a neurological reassessment.