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CASGEVY (exagamglogene autotemcel) - Severe sickle cell disease (SCD) in patients 12 years

Opinions on drugs - Posted on Sep 18 2024

Reason for request

First listing

Summary of opinion

Favourable opinion for reimbursement only in “the treatment of severe sickle cell disease (SCD) in patients 12 to 35 years of age with recurrent vaso-occlusive crises (VOCs) despite well managed hydroxycarbamide treatment for whom haematopoietic stem cell (HSC) transplantation is appropriate and a human leukocyte antigen (HLA)-matched related HSC donor is not available and the severity of the disease has been established by:

  • the implementation of a transfusion programme for at least 6 months for recurrent vaso-occlusive episodes (paediatric and adult population),
  • AND/OR, for the adult population only, the persistence of vaso-occlusive episodes having required conventional hospitalisation in the past year (≥ 2 episodes/year or ≥ 1 episode/year having required transfusion).

The Committee makes maintenance of the moderate clinical benefit conditional on reevaluation of the medicinal product within a maximum period of 3 years, based on the additional results requested.

Unfavourable opinion for reimbursement in the other situations covered by the MA indication.


Clinical Benefit
Moderate

The Committee deems that the clinical benefit of CASGEVY 4 to 13 x 106 cells/mL (exagamglogene autotemcel) is:

  • moderate in the treatment of severe sickle cell disease (SCD) only in patients 12 to 35 years of age with recurrent vaso-occlusive crises (VOCs) despite well managed hydroxycarbamide treatment for whom haematopoietic stem cell (HSC) transplantation is appropriate and a human leukocyte antigen (HLA)-matched related HSC donor is not available and the severity of the disease has been established by:
    • the implementation of a transfusion programme for at least 6 months for recurrent vaso-occlusive episodes (paediatric and adult population),
    • AND/OR, for the adult population only, the persistence of vaso-occlusive episodes having required conventional hospitalisation in the past year (≥ 2 episodes/year or ≥ 1 episode/year having required transfusion)

The Committee makes maintenance of the moderate clinical benefit conditional on reevaluation of the medicinal product within a maximum period of 3 years, based on the additional results requested.
Insufficient

The Committee deems that the clinical benefit of CASGEVY 4 to 13 x 106 cells/mL (exagamglogene autotemcel) is insufficient to justify public funding in the other MA situations.

Clinical Added Value
no clinical added value

Considering:

  • The available data, from the CLIMB-121 non-comparative pivotal study and the CLIMB-131 follow-up study, in favour of the efficacy of exagamglogene autotemcel on the short-term prevention of VOCs, with 96.6% of the patients having received the treatment not having presented any severe vaso-occlusive crises for 12 consecutive months over a 16-month follow-up period (primary endpoint of the CLIMB-121 study), clinically relevant endpoints for the disease,

But also considering:

  • The population on which the efficacy endpoint is measured, which raises questions since it excludes patients who were mobilised but discontinued the study before the administration of CASGEVY (exagamglogene autotemcel). In fact, the CASGEVY treatment strategy starts from the time of mobilisation. Hence, also considering patients having discontinued the study before receiving CASGEVY (exagamglogene autotemcel) (n=46) in the analysis, or those having discontinued the study before having received CASGEVY (exagamglogene autotemcel) but having started the mobilisation phase (n=40), the response rates for the primary endpoint were, respectively, 60.9% (CI95%: 45.4% - 74.9%, n=28/46) and 70.0% (CI95%: 53.5% - 83.4%, n=28/40),
  • The lack of comparative data enabling the value of this gene therapy to be assessed in comparison with current management,
  • The preliminary nature of these data, produced from interim analyses on a small number of patients (n=29) followed up for a short period of time, raising the question of a possible over-estimation of the effects presented and uncertainties with respect to the curative nature of this gene therapy, the mobilisation difficulties and its efficacy and safety in the longer term (particularly the theoretical tumour risk),
  • The potential heterogeneity of the patients in the study in terms of disease severity, which cannot be assessed due to a lack of sufficient data collected to document it,

the Committee deems that CASGEVY 4 to 13 x 106 cells/mL (exagamglogene autotemcel) provides no clinical added value (CAV V) in the current care pathway, which includes the relevant comparators.
Not applicable

Avis économique

Ce produit a fait l'objet d'un avis économique rendu par la Commission d'évaluation économique et de santé publique le 17/09/2024. 

L’avis économique porte sur une indication superposable à celle demandée au remboursement, à savoir les patients âgés de 12 ans et plus atteints d’une drépanocytose sévère présentant des crises vaso-occlusives récurrentes (CVO) éligibles à une greffe de cellules souches hématopoïétiques (CSH) et pour lesquels un donneur apparenté HLA (Antigène leucocytaire humain) compatible n’est pas disponible. 

La Commission évaluation économique et de santé publique conclut que :  

  • au prix modélisé (correspondant au PFHT revendiqué, et non pas au prix TTC conformément aux recommandations) pour une injection unique, et selon les hypothèses retenues dans la modélisation, la comparaison du traitement par CASGEVY (exagamglogene autotemcel) à la prise en charge standard, aboutit à un RDCR de 175 918 €/QALY (245 351 €/AV), sur un horizon temporel de 45 ans. 
  • ce RDCR n’est valable que dans la population recevant effectivement CASGEVY (exagamglogene autotemcel) et ne peut être transposé à la population totale visée par l’indication sollicitée au remboursement, comprenant les patients interrompant la stratégie de prise en charge avant l’administration de CASGEVY (exagamglogene autotemcel). Ce résultat est, par ailleurs, empreint d’une forte incertitude et, toutes choses égales par ailleurs, est particulièrement sensible : 
    • à l’efficacité du traitement sur les CVO sévères, dont l’effet est supposé maintenu dans le temps pour 90% des patients au-delà de 15 ans de simulation. Une incertitude demeure à moyen et long termes quant au maintien de cet effet, et l’exploration de l’incertitude liée à une éventuelle perte d’effet est insuffisante ;  
    • aux scores d’utilité appliqués aux états de santé du modèle, dont la robustesse ne peut être assurée au regard des données considérées et de la méthode d’estimation. 
    • l’introduction de CASGEVY (exagamglogene autotemcel) dans le panier de soins remboursables génère une augmentation des dépenses de l’Assurance Maladie d’environ 123% sur 3 ans. Ce résultat est incertain du fait de l’absence de considération des patients qui interrompent la stratégie de prise en charge avant l’administration de CASGEVY (exagamglogene autotemcel). 

La CEESP insiste sur la nécessité de conduire des analyses de l’efficience et de l’impact budgétaire sur l’ensemble des patients initiant la prise en charge évaluée (incluant les patients interrompant la stratégie de prise en charge avant l’administration de CASGEVY (exagamglogene autotemcel)). 

> CASGEVY Drépancytose sévère - Avis économique (pdf)

Documents

 

Economic analysis

English version

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