ASPAVELI (pegcetacoplan)

Key points

Favourable opinion for reimbursement in the treatment of adult patients with paroxysmal nocturnal haemoglobinuria (PNH) who are anaemic after treatment with a C5 inhibitor for at least 3 months, only in the event of haemoglobin levels <10.5 g/dL.

Unfavourable opinion for reimbursement in the other clinical situations of the MA.

What therapeutic improvement?

Therapeutic improvement in management of the disease.

Role in the care pathway?

The treatment of paroxysmal nocturnal haemoglobinuria (PNH) is currently based on eculizumab (SOLIRIS), blood transfusions in the event of severe anaemia and other symptomatic treatments without a validated indication in the treatment of PNH, such as anticoagulants.

Eculizumab (SOLIRIS), a complement inhibitor, is the only medicinal treatment with a reimbursed indication in PNH. This medicinal product is only reimbursed in adults with a history of transfusions. Although it has an MA in children and adults without a history of transfusions, eculizumab is not reimbursed in these populations, since the pharmaceutical company has not applied for its inclusion in the list. 

Bone marrow transplantation is currently the only treatment that can cure PNH but is only indicated in the event of associated severe bone marrow failure or myelodysplastic syndrome due to the complexity and risks associated with this procedure. If eculizumab treatment fails, allogeneic haematopoietic stem cell transplantation can sometimes be envisaged but these cases are very rare. In patients who have not responded to eculizumab treatment and who are not eligible for transplant, management is based on transfusions alone.

It should be noted that ravulizumab (ULTOMIRIS) has been granted an MA in adult patients with PNH who are complement inhibitor treatment-naïve or in patients who are clinically stable after having been treated with eculizumab for at least the past 6 months. Ravulizumab has no marketing authorisation in patients not having responded to eculizumab. To date, ravulizumab is not yet available on the French market in the absence of publication of a reimbursement rate and price in the French Official Journal, despite having received a favourable opinion for reimbursement from the Transparency Committee in September 2020.

Role of ASPAVELI (pegcetacoplan) in the care pathway:

Considering demonstration of the superiority of treatment with pegcetacoplan compared to the continuation of eculizumab in terms of increase in haemoglobin after 16 weeks, with a substantial effect size, in a restricted MA population, i.e. PNH patients who are anaemic, with Hb levels <10.5 g/dL despite treatment with eculizumab for at least 3 months, transfusion-dependent or otherwise, ASPAVELI (pegcetacoplan) is a second-line treatment in adult patients who are anaemic after treatment with a C5 inhibitor for at least 3 months, only in the event of haemoglobin levels <10.5 g/dL.

However, ASPAVELI (pegcetacoplan) has no role in the treatment of PNH in other clinical situations, due to a lack of data.

Its administration as a subcutaneous infusion makes home infusion and self-administration possible for patients who have tolerated treatment well in specialised treatment centres.

It should be noted that episodes of haemolysis that were serious and/or led to treatment discontinuation have been reported following the switch from eculizumab to pegcetacoplan. The severity of these episodes may be partially explained by the expansion of the PNH clone under C3 inhibitor treatment, according to expert opinion. Close monitoring with respect to this risk is therefore necessary in clinical practice. 

Finally, insofar as ASPAVELI (pegcetacoplan) is a complement protein C3 inhibitor that increases the patient’s predisposition to meningococcal infection or septicaemia due to its mechanism of action, the Transparency Committee reiterates that its prescription must be combined with vaccination against meningococcal infections using the ACYW conjugated tetravalent vaccine and the serogroup B invasive meningococcal infection vaccine, in accordance with the current SPC and subject to the opinion of the French High Council for Public Health (HCSP).

The Summary of Product Characteristics (SPC) and the Risk Management Plan (RMP) must be complied with.

This medicinal product is not recommended during pregnancy and in women of childbearing potential not using contraception (see SPC).

Special recommendations

Given the specificities of treatment of this rare disease, the Committee recommends that decisions to initiate or discontinue pegcetacoplan treatment be taken after a documented proposal resulting from a multidisciplinary team meeting within a reference or expert centre for the treatment of PNH. Regular follow-up of patients within one of these centres is essential to ensure the efficacy of treatment and monitor its safety, with particularly close monitoring in terms of the risk of the occurrence of episodes of haemolysis and thrombotic events.

Avis économique

Ce produit a fait l'objet d'un avis économique rendu par la Commission d'évaluation économique et de santé publique le 10 mai 2022.  

L’évaluation porte sur une indication plus restreinte que l’AMM à savoir le traitement de l’HPN chez les patients adultes après un traitement par inhibiteur de C5 pendant au moins 3 mois et présentant un taux d’hémoglobine < 10,5 g/dl. 

L’efficience du produit n’est pas démontrée sur la population pour laquelle une ASMR II est revendiquée en raison de 2 réserves majeures.  

Selon les termes de l’accord cadre du 5 mars 2021 conclu entre le CEPS et le Leem, lorsque le CA prévisionnel en 2e année de commercialisation est estimé inférieur à 50 millions d’euros HT, le choix d’intégrer dans le dossier une analyse d’impact budgétaire est laissé à la libre appréciation de l’industriel. Dans le cadre de ce dossier, aucune analyse d’impact budgétaire n’a été fournie par l’industriel. 

> ASPAVELI - avis économique (pdf)