Role of CVBF
The purpose of the DEEP Project has been to develop a new oral liquid formulation, suitable for children, of deferiprone (DFP) for the treatment of iron overload in paediatric patients affected by congenital anaemias, such as β-thalassaemia major (the so called “Mediterranean anaemia”) and sickle-cell disease (SCD), that require chronic transfusion therapy.
In particular, the Project included three studies aimed to evaluate the pharmacokinetics (DEEP-1 study), efficacy/safety (DEEP-2 study) and long-term safety (DEEP-3 study) of deferiprone in this specific patient population, in accordance with the Paediatric Investigation Plan (PIP) approved by the EMA Paediatric Committee (PDCO).
The DEEP Project provided the scientific evidence that the dosage per kilogram of DFP used in adults and older children can provide sufficient exposure to ensure efficacy also in younger children (DEEP-1 PK clinical trial that involved 21 patients under 6 years).
These results allowed children under the age of 6 years to be recruited in the safety/efficacy study (DEEP-2) that involved a total of 393 patients with the first patient first visit (FPFV) held in March 2014 and the last patient last visit (LPLV) in September 2017. This is the largest randomised trial in children with transfusion-dependent hemoglobinopathies comparing two oral chelating agents (deferiprone vs deferasirox) conducted so far, providing evidence to support the use of DFP in paediatric patients.
In addition, through the long-term observational safety study (DEEP-3) the nature and incidence of adverse effects of deferiprone in children and adolescents was evaluated. Started in 2013 and ended in October 2015, with 297 patients enrolled in the study, DEEP-3 confirmed that the safety profile of DFP in children and adolescents is in accordance with the available data in adults.
On the basis of the above-mentioned findings, a Paediatric Use Marketing Authorisation (PUMA) for the new formulation of deferiprone will be submitted in the upcoming months by the commercial partner of the project (ApoPharma Inc., which also provided financial support for the continuation of the project).
During the project particular attention has been payed to the development of age-tailored informative tools addressed to the children involved in the studies.
Seventh Framework Programme, European Commission
8.1 million euro
5.3 million euro
(1) Consorzio per le Valutazioni Biologiche e Farmacologiche (CVBF), Italy; (2) Universiteit Leiden, Olanda (UL), The Netherlands; (3) Azienda Ospedaliera Cardarelli (AOC), Italy; (4) National and Kapodistrian University of Athens (NKUA), Greece; (5) University Hospital Center “Mother Teresa” – National hemoglobinopathies Center (UHCT), Albania; (6) Cypriot Ministry of Health (CMoH), Cyprus; (7) Cairo University (CU), Egypt; (8) ApoPharma INC, Canada; (9)Fondazione Italiana Leonardo Giambrone per la guarigione dalla Thalassemia, Italy; (10) Azienda Ospedaliera Ospedali Riuniti “Villa Sofia-Cervello”, (AORC) Italy; (11) Azienda Ospedaliera di Padova, (AODP) Italy; (12) Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari, (PB) Italy; (13) APOTEX INC, Canada; (14) Universitätsklinikum Erlangen (UKER), Germany; (15) Centre National de Greffe de Moelle Osseuse (CNGMO), Tunis; (16) Fondazione per la Ricerca Farmacologica Gianni Benzi Onlus (FGB), Italy.