REPATHA (évolocumab ) - Hypercholestérolémie familiale hétérozygote (HFHe)

Key points

Favourable opinion for reimbursement in paediatric patients aged 10 years and over with heterozygous familial hypercholesterolaemia (HFHe), inadequately controlled (LDL-c > 1.30 g/L) by a maximum tolerated oral therapy, as an adjunct to diet, and:

• in combination with an optimised lipid-lowering therapy;

• or as monotherapy in the event of contraindication or known intolerance to both statins and ezetimibe.

Favourable opinion for reimbursement in paediatric patients aged 10 to 11 years with homozygous familial hypercholesterolaemia (HFHo) in combination with other lipid-lowering therapies.

Unfavourable opinion for reimbursement in the other clinical situations of the MA, in particular in the event of non-optimised lipid-lowering therapy.

What therapeutic improvement?

No clinical added value in the therapeutic strategy in of patients with HFHe.

Therapeutic improvement in the management of patients with HFHo.

Role in the care pathway?

Heterozygous familial hypercholesterolaemia in paediatric patients aged 10 years and over

Paediatric patients with HFHe with extremely high LDL-c levels should receive lipid-lowering therapy as soon as possible.

In other cases, if lifestyle and dietary measures have not been sufficient, statins are recommended as first-line therapy and are generally initiated from the age of 8 years. They should be started at the lowest recommended dose, which should be increased based on the patient’s response and tolerance to treatment.

In the event of failure of treatment with a statin at the maximum tolerated dose, combination with ezetimibe is recommended. In accordance with the guidelines, LDL-apheresis may be used in patients far from the cholesterol level goals (LDL-c >3 g/L) despite optimised lipid-lowering therapy. However, it should be noted that LDL-apheresis is very rarely practised in France.

Role of REPATHA (evolocumab) in the care pathway:

REPATHA (evolocumab) should be used as third-line treatment as an adjunct to lifestyle and dietary measures and in combination with an optimised oral lipid-lowering therapy*, or as monotherapy only in the event of contraindication or known intolerance to both statins and ezetimibe in children and adolescents aged 10 years and over with HFHe diagnosed in accordance with Wiegman’s criteria, inadequately controlled (LDL-c > 1.30 g/L) by a maximum tolerated oral lipid-lowering therapy.

REPATHA (evolocumab) has no role in the other clinical situations of the MA, in particular in combination with non-optimised lipid-lowering therapy.

 Homozygous familial hypercholesterolaemia in paediatric patients aged 10 to 11 years

The early identification of these children and their rapid management in a specialised centre is crucial.

The management of HFHo is based on the combination of lifestyle and dietary measures, early lipid-lowering therapy and lipoprotein apheresis if available.

Statins are recommended as first-line treatment. In the event of failure of treatment with a statin at the maximum tolerated dose, combination with ezetimibe is recommended.

In addition, LDL-apheresis is also recommended in HFHo patients.

Role of REPATHA (evolocumab) in the care pathway:

REPATHA (evolocumab) should be used as third-line treatment as an adjunct to lifestyle and dietary measures and in combination with an optimised oral lipid-lowering therapy*.

* As a reminder, optimised lipid-lowering therapy is defined as:

a statin at the maximum tolerated dose in combination with ezetimibe in the absence of contraindications or known intolerance       to statins and ezetimibe;

• a statin at the maximum tolerated dose alone in the event of contraindication or intolerance to ezetimibe;
• ezetimibe in the event of contraindication or known intolerance to statins.

Special recommendations

The Committee recommends that exception drug status be extended to this indication.

The Committee warns that there is a risk of misuse in populations not eligible for treatment, including, in particular, patients not receiving an optimised treatment where this is possible.

The Committee will pay particularly close attention to the real conditions of use of REPATHA (evolocumab) at its next assessments.