VYVGART (efgartigimod alfa) - Myasthénie

Key points

Approval of reimbursement only in addition to standard therapy, including first-line immunosuppressants, in adult patients with generalised myasthenia gravis who are  anti-acetylcholine receptor (AChR) antibody positive who remain symptomatic.

Disapproval of reimbursement for other marketing authorisation indication cohorts.

Therapeutic improvement?

Therapeutic improvement in the care pathway.

Role in therapeutic strategy?

Therapeutic management of myasthenia is based on several objectives: reducing symptoms and their impact on personal and work life as much as possible, managing serious life-threatening complications, limiting disease progression.

In cases where myasthenia is suspected or established, setting up symptomatic treatment with orally administered cholinesterase inhibitors, based on pyridostigmine bromide or ambenonium chloride, is recommended as a first-line approach.  

Long-term immunotherapy should be envisaged as soon as symptoms are not sufficiently or sustainably improved by cholinesterase inhibitors. First-line immunomodulatory treatment is based: 

• either on corticosteroids (prednisone or prednisolone),
  • or on immunosuppressants used off-label (azathioprine or alternatively mycophenolate mofetil),
  • or an association of both.

The choice of treatment is based on the onset of action, contraindications, and patient preferences.

In cases where myasthenia is uncontrolled under first-line immunomodulatory treatment or of intolerance to these treatments, the patient should be referred to a reference centre with a view to confirming the diagnosis, optimising the previous treatment and screen for exacerbating factors (contraindicated medicinal products, associated autoimmune disease, etc.). An off-label second-line immunotherapy regimen shall then be discussed with, as therapeutic options listed by the 2015 PNDS:

• rituximab, proposed in forms resistant to corticosteroids and to azathioprine,
• ciclosporin and tacrolimus, proposed in cases of myasthenia refractory to other treatments,
• and cyclophosphamide, reserved for specific indications (failure with other therapeutics, association with severe lupus).

The choice of treatment depends on the severity of the clinical profile, diathesis, onsets of action, and side-effects. Their efficacy must be assessed over 9 to 12 months. 

Non-medicinal alternatives are also available with surgical treatment (thymectomy) in cases of urgent thymoma regardless of myasthenia severity, except for elderly patients. Complementary radiotherapy is indicated in cases of macroinvasive thymoma. Chemotherapy is reserved for targeted indications, in particular for very extensive thymomas and in the case of metastases. International consensus recently updated5 the positioning of thymectomy in non-thymomatous generalised MG, based in particular on the MGTX randomised trial, and lists it as a therapeutic option to be envisaged at an early stage for patients aged 18 to 50 years with acetylcholine receptor (AChR) antibody-positive non-thymomatous generalised MG with the aim of minimising immunotherapy use. It is worth noting that thymectomy should be performed on neurologically stabilised patients.

In specific refractory myasthenia contexts, only the proprietary medicinal product SOLIRIS (eculizumab) has been granted a marketing authorisation for the treatment of refractory generalized myasthenia gravis in adult patients who are anti-acetylcholine receptor antibody-positive. However, as the pharmaceutical firm did not apply for its inclusion in the list for community use in this indication, the proprietary medicinal product is not currently covered for this indication (Transparency Committee opinion of 27 June 2018). Note that a pre-marketing authorisation early-access authorisation was granted for the proprietary medicinal product ULTOMIRIS (ravulizumab) on 19 May 2022 for the “treatment of generalised myasthenia gravis (gMG) in symptomatic refractory generalised myasthenia gravis patients, i.e. non-responders, ineligible for or intolerant to the treatments currently available and who are  anti-acetylcholine receptor (AChR) antibody-positive”, and for the proprietary medicinal product VYVGART (efgartigimod alfa) on 21 July 2022 “in association with standard therapy in adult patients with generalised myasthenia gravis who are anti-acetylcholine receptor (AChR) antibody-positive who remain symptomatic, and who are non-responders, ineligible for or intolerant to the alternatives currently available”.

The 2021 international consensus5 cites thymectomy as a therapeutic option in cases of failure to respond to an initial immunotherapy treatment or of intolerance to this treatment. 

Finally, in the case of acute and severe myasthenia episodes (including myasthenic crises), rapid, albeit temporary, improvement may be obtained with plasma exchanges (PLEX) or intravenous immunoglobulin injection (IVIG). The choice between IVIG and PLEX depends on their respective contraindications and hospital availability, particularly for PLEX. For some patients, regular (monthly) PLEX or IVIG may be required as a basic treatment (off-label use) in cases of intolerance or inefficacy of other treatments.

Role of VYVGART (efgartigimod alfa) in the therapeutic strategy:

Within the scope of reimbursement

VYVGART (efgartigimod alfa) is a first-line treatment in addition to standard therapy, including first-line immunosuppressants, in adult patients with generalised myasthenia gravis who are anti-acetylcholine receptor (AChR) antibody-positive who remain symptomatic, despite well-managed treatment.

Based on the current data, it is not possible to rank VYVGART (efgartigimod alfa) with respect to rituximab and anti-C5 treatments (SOLIRIS [eculizumab] and ULTOMIRIS [ravulizumab]), in the absence of comparative data.

Within the scope included in the marketing authorisation but not approved for reimbursement

VYVGART (efgartigimod alfa) has no role in such a context, given the lack of data in this cohort.

The summary of product characteristics (SPC) and the Risk Management Plan (RMP) must be adhered to.

Special recommendations

The Committee recommends updating the ‘Myasthenia’ PNDS and setting up a national Autoimmune Myasthenia registry.

Avis économique

Ce produit a fait l'objet d'un avis économique rendu par la Commission d'évaluation économique et de santé publique le 11 avril 2023

La demande de remboursement concerne la population des patients adultes atteints de myasthénie auto-immune généralisée présentant des anticorps anti-récepteurs de l’acétylcholine (RACh). La demande de remboursement est superposable à l’indication de l’AMM.

La CEESP a conclu que :

• les analyses économiques, fondées sur les années de vie gagnées ajustées par la qualité de vie et sur les années de vie gagnées, sont invalidées par la réserve majeure portant sur les données cliniques comparatives ;
• l'analyse d'impact budgétaire, incluant le ravulizumab dont le développement et l’accès au marché est concomitant, est invalidée en raison de la robustesse non assurée des données cliniques mobilisées. Par conséquent l’impact budgétaire lié à l’introduction du produit demeure inconnu.

> VYVGART - Avis économique (pdf)