Reason for request
Favourable opinion for reimbursement only in children with Noonan syndrome with growth retardation defined by a current height < -2 SDS.
What therapeutic improvement ?
No clinical added value in the therapeutic strategy.
Role in the care pathway ?
The management of patients with Noonan syndrome is symptomatic and multidisciplinary. Its objective is to ensure the early diagnosis and treatment of the various associated abnormalities and medical complications: heart conditions and arrhythmias, undernutrition and delayed growth, neurosensory abnormalities and cognitive difficulties, orthopaedic abnormalities, etc. Patient education and specialised medical follow-up are essential in these patients.
The aim of treatment for growth retardation is, firstly, to normalise height during childhood and, secondly, to normalise height during adulthood. Growth hormone treatment may be envisaged in the absence of hormone deficiency to promote short and long-term growth.
At present, several proprietary medicinal products exist containing somatropin: GENOTONORM, NUTROPINAQ, OMNITROPE, UMATROPE, SAIZEN, NORDITROPIN and ZOMACTON; but only NORDITROPIN has an MA in the treatment of growth retardation due to Noonan syndrome. Regular follow-up of growth and skeletal development should be conducted every six months during the growth phase.
Role of the medicinal product in the care pathway
NORDITROPIN (somatropin) is a first-line treatment that should be reserved for children with Noonan syndrome with growth retardation defined by a current height < -2 SDS according to general population growth charts. It is the only somatropin-based medicinal product to have an MA in this indication in France.
In these patients, the Committee recommends initiating treatment with NORDITROPIN :
- following the resolution of eating disorders, associated or otherwise with inadequate weight gain, in a context in which these disorders are common before the age of 2 years and the clinical data assessing the efficacy and safety of somatropin concern prepubertal children aged at least 3 years ;
- after having established a genetic diagnosis, enabling optimised treatment of Noonan syndrome ;
- at the lowest dose in the SPC, i.e., 0.033 mg/kg/day. The dosage must be tailored to each patient and may be adjusted every 6 months on the basis of the clinical response (growth rate and height) and tolerance to treatment, via monitoring of IGF-1 levels.
Furthermore, considering the complexity of treatment of this disease and the risks associated with the administration of this medicinal product, the Committee recommends that the prescription of NORDITROPIN (somatropin) be reserved for specialists in growth retardation (paediatric endocrinologists) and that follow-up of these patients be coordinated by reference or expertise centres in this disease.
In accordance with its SPC, treatment with NORDITROPIN (somatropin) should be discontinued at the time of closure of the epiphyseal growth plates.
The Committee reiterates that the long-term effects of somatropin are not known (maximum follow-up of 4 years of treatment in a clinical study, few data on adult height).
The Committee deems that the clinical benefit of NORDITROPIN (somatropin) is substantial only in children with Noonan syndrome with growth retardation defined by a current height < -2 SDS.
Clinical Added Value
|no clinical added value||
the Committee considers that NORDITROPIN (somatropin) proprietary medicinal products provide no clinical added value (CAV V) in the care pathway for growth retardation due to Noonan syndrome.