XENPOZYME (olipudase alfa) - Maladie rare

Opinions on drugs - Posted on Dec 16 2022

Reason for request

First assessment

Key points

Approval of reimbursement for the enzyme replacement therapy for the treatment of non-Central Nervous System (CNS) manifestations of Acid Sphingomyelinase Deficiency (ASMD) in paediatric and adult patients with type A/B or type B.

Therapeutic improvement?

Therapeutic improvement in the care pathway.

Role in therapeutic strategy?

There is currently no authorised or off-label treatment for ASMD. Reducing hepatosplenomegaly and hence correcting blood and lipid disorders, as well as improving respiratory function may improve the patient’s state of health.

The current treatment of ASMD is multidisciplinary and symptomatic, and is based on:

For cytopenia: blood transfusions (packed red blood cells) and antibiotic therapy (neutropenia),
For lung involvement: corticosteroids or bronchodilators by the inhalation route. Anecdotal cases of pulmonary lavage, lung or bone marrow transplantation have been reported. Long-term oxygen therapies and/or continuous positive airway pressure (CPAP) therapy may also be required.
For bone density: calcium and vitamin supplementation (vitamin D),
For hypercholesterolaemia: high-dose statins (with close monitoring) and low-fat diet.

Splenectomy is not recommended as it is associated with a risk of pulmonary exacerbation and an increased risk of mortality.

Liver involvement must be monitored, including screening for oesophageal varix (non-selective beta-blocker prophylaxis) in patients with portal hypertension.

Lifestyle and dietary measures with a reduction in alcohol consumption, and a tailored diet must be implemented.

Role of the medicinal product

XENPOZYME (olipudase alfa) is a first-line treatment for the enzyme replacement therapy for the treatment of non-Central Nervous System (CNS) manifestations of Acid Sphingomyelinase Deficiency (ASMD) in paediatric and adult patients with type A/B or type B.

The Committee recommends that the decisions for treatment initiation and
discontinuation of XENPOZYME (olipudase alfa) are made in ASMD reference and expert centers.

Clinical Benefit

Substantial

The Committee deems that the clinical benefit of XENPOZYME (olipudase alfa) is significant in the marketing authorisation indication.

Clinical Added Value

moderate

Considering:

the evidence of the superiority of olipudase alfa versus placebo in adults after 52 weeks of treatment in terms of:
- relative spleen volume variation of -39.9% (95%CI [-47.05; -32.80]; p<0.0001) and relative DLCO variation of +19.0% (95%CI [9.32; 28.70]; p=0.0004) (primary outcome measures),
- relative liver volume variation of -26.6% (95%CI [-33.91; -19.28]; p<0.0001) and relative platelet count variation of +14.3% (95%CI [2.56; 26.10]; p=0.0185) (ranked secondary outcome measures),
the efficacy which appears to be maintained at 104 weeks in adults, but based on limited data from the extension study,
a suggested efficacy of olipudase alfa in children after 52 weeks of treatment on similar outcome measures to those assessed in adults in a non-comparative study,

but in view of:

the lack of probative data on quality of life in adults and in children, while quality of life is particularly impaired in this disease,
the lack of evidence of an impact on mortality in a condition in which life expectancy is reduced,
the favourable safety profile in both populations, wpe B.ith however infusion-related reactions, of higher incidence in the paediatric population than the adult population, and serious adverse events linked with olipudase alfa treatment reported in children (anaphylactic shock, diffuse urticaria and ALAT > 10 UNL), with limited long-term safety follow-up in both populations,

the Committee deems that XENPOZYME (olipudase alfa) provides moderate clinical added value (CAV III) in the therapeutic strategy of enzyme replacement therapy for the treatment of non-Central Nervous System (CNS) manifestations of Acid Sphingomyelinase Deficiency (ASMD) in paediatric and adult patients with type A/B or type B.

Avis économique

Ce produit a fait l'objet d'un avis économique rendu par la Commission d'évaluation économique et de santé publique le 28 février 2023.

L’avis économique porte sur une indication superposable à celle demandée au remboursement, à savoir le traitement des manifestations non-neurologiques du déficit en sphingomyélinase acide (Acid Sphingomyelinase Deficiency, ASMD) de type B et A/B chez les patients pédiatriques et adultes.

La CEESP n’a pas été en mesure de conclure sur l’efficience du produit, en raison des deux réserves majeures invalidant les résultats de l’évaluation économique dans les deux populations.

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.

> XENPOZYNE - Avis économique (pdf)

Documents

Economic analysis

English version

XENPOZYME 231122 SUMMARY CT19922

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