From class waivers to precision medicine in paediatric oncology

10-year report on the European Paediatric Regulation and its impact on new drugs for children's cancers

“…Forty eight (54%) of these 89 drugs had a MOA warranting paediatric development. Two (2%) drugs were considered not relevant and 16 (18%) required further data 5 .…”

“…Supported by these analyses, we proposed a MOA-based approach with five initiatives: (i) an aggregated database of paediatric biological tumour drug targets; (ii) a joint academicpharmaceutical industry pre-clinical platform to analyse the activity of new drugs (Innovative Therapy for Children with Cancer Paediatric Preclinical Proof-of-Concept Platform: ITCC-P4); (iii) Paediatric Strategy Forums; (iv) molecular profiling of paediatric tumours at diagnosis and relapse; and (v) the suppression of article 11b of the European Paediatric Regulation, which allows productspecific waivers on the grounds that the associated condition does not occur in children 5 . The first three of these have been implemented: a database of targets has been created 6 , -and the ITCC-P4 has been funded as an IMI2 project and is operational 7 .…”

Pediatric Development of Molecularly Targeted Oncology Drugs

“…In another retrospective review of European Pediatric Regulation between 2012 to 2015, 48 (54%) of the 89 class‐waivered drugs were characterized as warranting pediatric development based on MOA. This determination was made based on prespecified criteria initially supported by a literature search confirmed by group of experts ( n = 15) in the field achieving consensus (70%) . This review confirms that pediatric oncology product development guided by MOA has the ability to accelerate new therapeutic options.…”

Pharmacokinetic Targets for Therapeutic Drug Monitoring of Small Molecule Kinase Inhibitors in Pediatric Oncology

“…Julie M. Janssen 1, *, Thomas P. C. Dorlo 1 , Neeltje Steeghs 2 , Jos H. Beijnen 1,3 , Lidwien M. Hanff 4 , Natasha K. A. van Eijkelenburg 4 , Jasper van der Lugt 4 , C. Michel Zwaan 4,5 and Alwin D. R. Huitema 1,6 In recent years new targeted small molecule kinase inhibitors have become available for pediatric patients with cancer. Relationships between drug exposure and treatment response have been established for several of these drugs in adults.…”

“…2,3 However, since the type of adult cancer for which a drug is approved often does not occur in children, waivers are frequently granted for pediatric development, and it has been argued that in fact a target-based waiver system would be more appropriate. 4 Up to 2016, only two KIs had been approved by the US Food and Drug Administration (FDA) for the treatment of childhood cancers: Imatinib for Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) and everolimus for subependymal giant-cell astrocytoma. 2,3 Only recently, dasatinib, nilotinib, and larotrectinib have been approved by the FDA for the treatment of pediatric cancers.…”