Download opinion
Add to my selection
Quote this publication Print

ADAKVEO (crizanlizumab)

Opinions on drugs - Posted on May 07 2021

Reason for request

First assessment

Key points

Favourable opinion for reimbursement in the prevention of recurrent vaso-occlusive crises (VOCs) in sickle cell disease patients aged 16 years and older. It can be given as an add-on therapy to hydroxyurea/hydroxycarbamide (HU/HC) or as monotherapy in patients for whom HU/HC is inappropriate or inadequate.

Maintenance of this opinion is subject to submission of the results of the phase 3 study comparing crizanlizumab with placebo and data from the registry of patients treated in France; the Committee will conduct a reevaluation within a maximum period of 4 years.

What therapeutic improvement?

No clinical added value on the basis of currently available data.

Role in the care pathway?

Acute complications of sickle cell disease, such as vaso-occlusive crises, acute chest syndromes, priapism and stroke are therapeutic emergencies. The disease-modifying therapies currently available treat the anaemia (blood transfusions) and reduce HbS levels (hydroxycarbamide and exchange transfusions). Haematopoietic stem cell transplantation is currently the only curative treatment. Reserved for severe forms, it is generally performed using an HLA-identical sibling donor.

Hydroxycarbamide is effective for reducing the frequency and severity of painful episodes in children and adults, as well as relapses of acute chest syndrome in adults. Hydroxycarbamide remains the reference treatment in the prevention of recurrent vaso-occlusive crises (VOCs) in sickle cell disease patients aged 16 years and older.

Role of the medicinal product in the care pathway

Considering:

  • the medical need in this disease, particularly in patients for whom treatment with hydroxycarbamide is inappropriate or inadequate,
  • the available preliminary data from a phase 2 study demonstrating a modest effect size (with only 1.35 vaso-occlusive crises avoided compared to placebo) in a heterogeneous population in terms of severity and history of treatment with hydroxycarbamide
  • the results of this study, which do not enable the role of ADAKVEO (crizanlizumab) to be positioned compared to hydroxycarbamide, the reference treatment with established efficacy in the prevention of vaso-occlusive crises,
  • the short follow-up period in terms of efficacy and safety (1 year),

the Transparency Committee considers, that as the dossier currently stands, crizanlizumab cannot replace well-managed hydroxycarbamide treatment at an appropriate dose for an adequate treatment duration, after having checked good compliance with this treatment. Consequently, treatment with crizanlizumab should preferentially be envisaged as add-on therapy to hydroxycarbamide. However, according to its SPC crizanlizumab can be prescribed as monotherapy only in patients in whom HU/HC treatment is inappropriate or inadequate.


Clinical Benefit
Low

The Committee deems that the clinical benefit of ADAKVEO (crizanlizumab) is low in the MA indication.

 

Clinical Added Value
no clinical added value

Considering:

  • a modest efficacy demonstrated in a phase 2 study of crizanlizumab compared to placebo in terms of reduction in median annual rate of VOCs with a reduction of only 1.35 crises per year with crizanlizumab (median annual rate of vaso-occlusive crises in the crizanlizumab 5.0 mg/kg group of 1.63 [0.0-24.3] versus 2.98 [0.0-24.3] in the placebo group; Hodges-Lehmann median absolute difference of -1.01, CI95% [-2.00; 0.00]), p=0.010),
  • an efficacy assessed in a heterogeneous patient population in terms of disease severity, with the majority of patients having a low annual rate of crises (i.e., 2 to 4 crises during the year prior to inclusion for 62.6% of patients) and a minority of patients (37.4%) having between 5 and 10 vaso-occlusive crises in the year prior to inclusion; hence a majority of patients treated with hydroxycarbamide at inclusion (62.1%),
  • the impossibility of estimating the effect size of crizanlizumab, firstly, as monotherapy in patients for whom hydroxycarbamide is inappropriate or inadequate, and, secondly, as add-on therapy to hydroxycarbamide related to the heterogeneity of the population included,
  • the safety profile of crizanlizumab that seems to be favourable, with however less than 1 year of follow-up,
  • the lack of efficacy and safety data for crizanlizumab compared to the reference treatment, hydroxycarbamide,

the Committee considers that ADAKVEO (crizanlizumab) provides no clinical added value (CAV V) in the prevention of recurrent vaso-occlusive crises (VOCs) in sickle cell disease patients aged 16 years and older, as an add-on therapy to hydroxyurea/hydroxycarbamide (HU/HC) or as monotherapy in patients for whom HU/HC is inappropriate or inadequate.

 

 

Documents

English version

Contact Us

Évaluation des médicaments
All our publications