VYEPTI (eptinezumab)

Key points

Approval of reimbursement only in preventive treatment of migraine in patients suffering from severe migraine with at least 8 migraine days per month, who have failed to respond to at least two prophylactic treatments and are free from cardiovascular impairment (patients having had myocardial infarction, stroke, TIA, unstable angina or coronary bypass surgery).

Disapproval of reimbursement in other marketing authorisation situations.

Therapeutic improvement?

No progress in management.

Role in therapeutic strategy?

Migraine management is based on both treating acute episodes and, if necessary, on introducing a basic prophylactic treatment to reduce 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. It should be noted that topiramate has been the subject of a recent report on the risk of autism spectrum disorders and intellectual disability in children exposed during pregnancy and is therefore contraindicated for migraine in pregnant women and in women of childbearing age who are not using a highly effective method of contraception, pending the conclusions of the European assessment. Amitriptyline (LAROXYL film-coated tablet and oral solution proprietary medicinal products) is also indicated for the basic treatment of migraine in adults. This indication has not been evaluated 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 for episodic migraine where beta blocker treatment is inappropriate.

In the event of failure to respond to these treatments, 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 days of migraine per month, failing to respond to at least two prophylactic treatments, and free from cardiovascular impairment,
• 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 chronic migraine prophylaxis in patients who have failed to respond 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 VYEPTI (eptinezumab) in the therapeutic strategy:

In view of:

• the efficacy data from the DELIVER study in patients who have failed to respond to 2-4 prophylactic regimens, and of the need in this clinical situation,
• the fact that patients with at least 8 migraine days per month represented the majority of patients included in the efficacy studies,the uncertainty about cardiac safety observed in patients from the different studies, while patients with severe cardiovascular disease were excluded by the protocols; this uncertainty remains despite the long-term data on the safety of the anti-CGRP antibody medicinal product class,
• the fact that patients with at least 8 migraine days per month represented the majority of patients included in the efficacy studies,
• the uncertainty about cardiac safety observed in patients from the different studies, while patients with severe cardiovascular disease were excluded by the protocols; this uncertainty remains despite the long-term data on the safety of the anti-CGRP antibody medicinal product class,

• the Committee deems that VYEPTI (eptinezumab) provides a medication option for patients suffering from severe migraine with at least 8 migraine days per month, who have failed to respond to at least two prophylactic treatments and are free from cardiovascular impairment (patients having had myocardial infarction, stroke, TIA, unstable angina or coronary bypass surgery).

  The Committee stresses, in accordance with the clinical guidelines, that the benefit of the treatment must be assessed within 6 months after 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. It should be recalled that, unlike previous anti-CGRP antibodies evaluated by the Committee, which are administered subcutaneously, VYEPTI (eptinezumab) is administered as an intravenous infusion with the need for monitoring during and after the infusion, paying particular attention to anaphylactic reactions that may occur during treatment.

  Furthermore, the Committee underlines that current data on the use of eptinezumab in pregnant women is limited (see clinical guidelines). As a precautionary measure, the use of VYEPTI (eptinezumab) should be avoided during pregnancy.