ZYNTEGLO (bétibéglogène autotemcel)

• Key points

Favourable opinion for reimbursement only in the treatment of patients over 12 years and under 35 years of age with transfusion-dependent β-thalassaemia (TDT) who do not have a β0/β0 genotype, for whom haematopoietic stem cell (HSC) transplantation is appropriate but a human leukocyte antigen (HLA)-matched related HSC donor is not available.

This opinion will be reassessed within a maximum period of 3 years on the basis of data collected in a registry and all the use, efficacy and safety data available.

• What therapeutic improvement?

Therapeutic improvement in the treatment of non β0/β0 genotype patients ≥ 12 years and < 35 years of age with transfusion-dependent β-thalassaemia (TDT), for whom HSC transplantation is appropriate but who do not have a matched related donor.

• Role in the care pathway?

For patients without an HLA-matched related HSC donor unable to benefit from allogeneic HSC transplantation, which is the only curative treatment for transfusion-dependent β-thalassaemia (TDT) for patients with an HLA-matched related HSC donor, the only treatment is based on life-long frequent and regulator red cell concentrate transfusions along with iron chelating agents. In France, HSCT is only discussed in exceptional cases in patients with an HLA-matched unrelated HSC donor if it is impossible to continue transfusion (allo-immunisation) or chelator therapy.

Role of ZYNTEGLO in the care pathway:

ZYNTEGLO has demonstrated efficacy on transfusion independence (with a maximum follow-up of 5 years for 3 patients only), and therefore represents an alternative to standard life-long symptomatic treatment with blood transfusions combined with iron chelation therapy, for patients with transfusion-dependent β-thalassaemia (TDT), who do not have a β0/β0 genotype, for whom haematopoietic stem cell (HSC) transplantation is appropriate but a human leukocyte antigen (HLA)-matched related HSC donor is not available.

ZYNTEGLO can be prescribed on the basis of two cumulative conditions:

1) age: since ZYNTEGLO has only been assessed in patients under the age of 35 years, given uncertainties in terms of its efficacy and safety in older patients, only patients aged from 12 years up to 35 years may be eligible for ZYNTEGLO treatment. In the absence of any assessment of the clinical benefit in patients aged over 35 years, these patients must not be treated with ZYNTEGLO.

2) treatment history: ZYNTEGLO has only been evaluated in patients treated and followed up for at least 2 years in a specialised centre and who are clinically stable. Therefore ZYNTEGLO is not intended to be administered from the outset in a newly diagnosed or newly treated patient but is aimed only at patients having already received optimal standard treatment in terms of transfusion and chelation, for a period of at least 2 years in a specialised centre.

• Special recommendations

Given the uncertainties with respect to the long-term efficacy and safety ZYNTEGLO, treatment in a specialised centre and the provision of information for patients and their family (depending on the patient’s age) is essential.

In particular, the risk to fertility of ZYNTEGLO treatment, related to the administration of busulfan during the conditioning phase, means that the issue of preservation of fertility or a potential pregnancy needs to be discussed with patients and their family (depending on the patient’s age). According to the SPC, it is advised to cryopreserve semen or ova before treatment if possible.

The Committee will reassess ZYNTEGLO within a maximum period of 3 years on the basis of data collected in a registry and all the use, efficacy and safety data available.

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