On September 21st 2017, Sebastian Botzenhardt, researcher involved in DEEP project (DEEP PhD), held the final examination for his doctoral thesis at Friedrich-Alexander-University Erlangen-Nuremberg, where he exposed the overall results of a study aimed to assess the drug safety profile of oral chelator deferiprone (DFP) in children, by aggregating available data from the scientific literature and by generating new safety data. His work was supervised by PD Dr. Antje Neubert in the context of the DEEP project and has availed itself of the support of the independent DEEP Consortium in order to generate data on pharmacokinetics, efficacy and safety of DFP in children affected by hereditary transfusion-dependent haemoglobinopathies. As DFP may be the only viable iron chelation therapy option for some children, the European Medicines agency (EMA) included DFP on their priority list for studies on off-patent paediatric medicinal products. Hereditary haemoglobin disorders, in fact, represent a significant health problem with over 330.000 affected newborns per year. Currently, three agents are available for the treatment of iron overload: deferoxamine (DFO), deferiprone (DFP) and deferasirox (DFX).
Botzenhardt’s thesis comprises three parts. The first part is a systematic literature review with meta-analyses of published safety data of DFO, DFP, DFX and combination regimens in young patients aged under 25 years with transfusion-dependent haemoglobinopathies. The second part is a retrospective observational cohort study using population-based data from an electronic health record database in Hong Kong. Diagnosis codes, hospital admission data and laboratory results of Chinese thalassaemia patients under the age of 18 years were utilised to identify potential adverse effects (AEs). The third part coincides with the DEEP-3 observational safety study: a multi-national, retro- and prospective cohort study investigating the long-term safety of DFP treatment in paediatric patients aged under 18 years from the Mediterranean region. Medical patient data and possible AEs to DFP were collected between 2012 and 2016 from 16 thalassaemia centres in Albania, Cyprus, Egypt, Greece, Italy and Tunisia. The coordinating centre was the “Azienda Ospedaliera di Padova – AODP”.
Overall, the data collected in these studies highlighted that the safety profile of DFP in children and adolescents obtained from the systematic literature review and the two pharmacoepidemiology studies is in accordance with the latest information in SPCs (Summary of Products Characteristics) and manufacturer post-marketing data. Moreover, there was no evident increased risk for ADRs in children under the age of 10 years or in patients with combined therapy with DFO. The risk for agranulocytosis in children treated with DFP is comparable to older patients.