Reason for request
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
- 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.
The Committee deems that the clinical benefit of ADAKVEO (crizanlizumab) is low in the MA indication.
Clinical Added Value
|no clinical added value
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.