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ONUREG 200 - 300 mg (azacitidine)

Opinions on drugs - Posted on Jan 10 2022

Reason for request

First assessment

Key points

Favourable opinion for reimbursement as maintenance therapy in adult patients with acute myeloid leukaemia (AML) who achieved complete remission (CR) or complete remission with incomplete blood count recovery (CRi) following induction therapy with or without consolidation treatment and who are not candidates for, including those who choose not to proceed to, hematopoietic stem cell transplantation (HSCT).

What therapeutic improvement?

Therapeutic improvement compared to no therapy with monitoring.  

Role in the care pathway?

For patients having obtained CR/CRi and not eligible for HSCT, maintenance therapy may be considered. This approach is aimed at delaying relapse and prolonging the duration of remission and survival, particularly in patients with intermediate or high risk.

Midostaurine (RYDAPT) is indicated in the treatment of AML with an indication restricted to patients with AML who are FLT3 mutation-positive in combination with standard induction chemotherapy and consolidation chemotherapy, followed by RYDAPT (midostaurine) single agent maintenance therapy, in the absence of HSCT. This FLT3 mutation concerns around 30% of AML cases.

In its opinion of 13/06/2018 relative to RYDAPT (midostaurine), the Transparency Committee nonetheless highlighted that it is impossible to determine the specific contribution of maintenance therapy with RYDAPT (midostaurine) in patients not having undergone allogeneic SCT in the absence of randomisation before the initiation of maintenance therapy, in view of the study design in the RATIFY pivotal study.

The current strategy in the maintenance therapy of AML consists of clinical and laboratory monitoring.

Role of ONUREG (azacitidine) in the care pathway?

ONUREG (azacitidine) is a maintenance therapy in adult patients with AML who achieved complete remission (CR) or complete remission with incomplete blood count recovery (CRi) following induction therapy with or without consolidation treatment and who are not candidates for hematopoietic stem cell transplantation (HSCT). Its superiority has been established versus placebo in terms of overall survival and relapse-free survival over a median follow-up period of 41.2 months.

In patients with an FLT3 mutation, in the absence of comparative data and given the impossibility of determining the specific contribution of maintenance therapy with RYDAPT (midostaurine) in patients not having undergone allogeneic SCT (see opinion of 13/06/2018 concerning RYDAPT), the role of ONUREG (azacitidine) compared to RYDAPT (midostaurine) cannot be determined.

 

 

 

 


Clinical Benefit

Substantial

The Committee deems that the clinical benefit of ONUREG (azacitidine) is substantial in the MA indication.


Clinical Added Value

moderate

Considering:

  • demonstration of the superiority of ONUREG (azacitidine) versus placebo in terms of overall survival, the primary endpoint, with an absolute increase of 9.9 months (HR = 0.69; CI95% = [0.55; 0.86], p = 0.0009),
  • demonstration of the superiority of ONUREG (azacitidine) versus placebo in terms of relapse-free survival (ranked secondary endpoint), with an absolute increase of 5.3 months (HR = 0.65; CI95% = [0.52; 0.81], p = 0.0001),
  • the safety profile of ONUREG (azacitidine) deemed to be acceptable but marked by the occurrence of adverse events, particularly haematological and gastrointestinal events,
  • the unmet medical need in the maintenance therapy of AML,

and despite:

  • the absence of robust quality of life data in comparison with no therapy with monitoring, in particular the absence of data supporting maintenance of quality of life in patients receiving long-term treatment with ONUREG (azacitidine) in view of its safety profile,

the Committee considers that ONUREG (azacitidine) as maintenance therapy provides a moderate clinical added value (CAV III) compared to no therapy with monitoring, in adult patients with AML who achieved CR or CRi following intensive therapy and who are not candidates for hematopoietic stem cell transplantation.

 


Avis économique

Ce produit a fait l'objet d'un avis économique rendu par la Commission d'évaluation économique et de santé publique le 15 novembre 2021. L’avis économique porte sur une indication superposable à celle demandée au remboursement, à savoir dans le « traitement de maintenance chez les patients adultes atteints de leucémie aiguë myéloïde (LAM) ayant obtenu une rémission complète (RC) ou une rémission complète avec récupération incomplète de la numération formule sanguine (RCi) après une thérapie d'induction avec ou sans traitement de consolidation, et qui ne sont pas candidats (incluant les patients qui font le choix de ne pas procéder) à une greffe de cellules souches hématopoïétiques (GCSH).»

Au prix revendiqué par l’industriel pour une boîte de 7 comprimés de 300 mg de l’azacitidine orale, l’analyse de référence de l’efficience de l’azacitidine orale aboutit à un RDCR de 545 599 €/QALY vs « l’observation sans traitement ». Ce résultat doit être interprété avec prudence en raison de l’absence non justifiée de données de qualité de vie décrivant la phase post-rechute par l’industriel.

 Il n’y a pas d’analyse d’impact budgétaire déposée pour ce dossier.

> ONUREG - Avis économique (pdf)

 

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