AIMOVIG (érénumab) - Migraine

Key points

Favourable opinion for reimbursement only in patients with severe migraine and at least 8 migraine days per month, with previous failure to at least two prophylactic treatments and without cardiovascular disease (patients having had a myocardial infarction, stroke, TIA, unstable angina or coronary artery bypass graft (CABG)).

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

What therapeutic improvement?

No clinical added value in the therapeutic strategy.

Role in the care pathway?

The management of migraine is based on both the treatment of attacks and, if necessary, the initiation of long-term prophylactic treatment to reduce the frequency of attacks.

The medicinal products used in the treatment of attacks are non-specific migraine treatments (analgesics and nonsteroidal anti-inflammatories) and specific treatments (triptans, mainly and ergot derivatives).

The choice of prophylactic treatment is based on the side effects, contraindications, interactions and any concomitant conditions the patient may have. The drugs with a MA in the prophylactic treatment of migraine that are used as first-line treatment are beta-blockers (metoprolol and propranolol) and topiramate. Amitriptyline (LAROXYL film-coated tablets and oral solution) also has an indication in the prophylactic treatment of migraine in adults. This indication has not yet been assessed by the Committee. The recent 2021 guidelines issued by the French Society for Migraine and Headache Studies position amitriptyline as a first-line treatment for episodic migraine in the event of failure of or contraindication to beta-blockers.

If these treatments fail, the salvage therapies for the prophylaxis of migraine are as follows:

• oral treatment with a MA for the prophylactic treatment of migraine (pizotifen, oxetorone, flunarizine) but used as salvage therapies only due to their safety profile, in particular,
• anti-CGRP antibodies (erenumab [AIMOVIG], galcanezumab [EMGALITY] and fremanezumab [AJOVY]), which are alternatives in patients with severe migraine who have 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 type A) with a recent indication extension specifically in chronic migraine (presence of headaches at least 15 days per month, including at least 8 migraine days per month), recently assessed by the Transparency Committee (CT opinion of 17 November 2021); this is a medicinal option for the prophylactic treatment of chronic migraine in adult patients who have not responded or are intolerant to other prophylactic oral migraine treatments.

Other drugs are also used off-label in the prophylactic treatment of migraine with a lower level of evidence of their efficacy (high to moderate): anti-epileptic medicinal products (sodium valproate and divalproate), beta-blockers (atenolol, nebivolol, timolol), candesartan.

Role of AIMOVIG (erenumab) in the care pathway within the scope of the indication that is the subject of this re-evaluation:

In view of:

• the efficacy data for erenumab versus placebo, obtained from the previously assessed LIBERTY study in patients with previous failure to 2 to 4 prophylactic treatments and most of whom have at least 8 migraine days per month, and of the medical need in these patients, having led, in particular, to the recommendation for reimbursement in this situation,
• new comparative data, having demonstrated the superiority versus topiramate on the rate of treatment discontinuations due to an adverse event (primary safety endpoint in the HER-MES study), in a predominantly treatment-naïve population (59.4%) or with previous failure to only one treatment (30.7%) and therefore not recommended for reimbursement,
• the uncertainty with respect to the cardiac safety that emerged in patients in the various studies, although patients with severe cardiovascular disease were excluded by the protocols, with this uncertainty persisting despite the new safety data,

the Committee considers that AIMOVIG (erenumab) remains a medicinal option in patients with severe migraine and at least 8 migraine days per month, with previous failure to at least two prophylactic treatments and without cardiovascular disease (patients having had a myocardial infarction, stroke, TIA, unstable angina or coronary artery bypass graft (CABG)).

The new data is not likely to modify the role of AIMOVIG (erenumab) in the care pathway previously determined by the Committee in its inclusion opinion of 27 February 2019.

It is highlighted that the LIBERTY study was conducted at the 140 mg/month dose only and that AIMOVIG (erenumab), according to its SPC, can be administered at a dosage of 70 or 140 mg/month. There are no criteria to define which patients will benefit from one or other of the doses at treatment initiation and how the dosage adjustment (dose increase or reduction) should be implemented.

The Committee highlights the fact that, in accordance with the SPC, the benefit of the treatment should be assessed in the 3 months following the initiation of treatment and the decision whether to continue it should be taken on a case-by-case basis, with regular evaluation of the clinical response recommended thereafter.

Efficacy data beyond one year of treatment remains limited. According to expert opinion, a neurological reassessment should be performed for continuation of treatment beyond a period of one year.