Changing incentives to ACCELERATE drug development for paediatric cancer

Abstract

Background: More effective incentives are needed to motivate paediatric oncology drug development, uncoupling it from dependency on adult drug development. Although the current European and North-American legislations aim to promote drug development for paediatrics and rare diseases, children and adolescents with cancer have not benefited as expected from these initiatives and cancer remains the first cause of death by disease in children older than one. Drug development for childhood cancer remains dependent on adult cancer indications and their potential market. The balance between the investment needed to execute a Paediatric Investigation Plan (PIP) in Europe and an initial Paediatric Study Plan (iPSP) in the US, coupled with the potential financial reward has not been sufficiently attractive to incite the pharmaceutical industry to develop drugs for rare indications such as childhood cancer.

Methods: We propose changes in the timing and nature of the rewards within the European Paediatric Medicine Regulation (PMR) and Regulation on Orphan Medicinal Products (both currently under review), which would drive earlier initiation of paediatric oncology studies and provide incentives for drug development specifically for childhood indications.

Results: We suggest modifying the PMR to ensure mechanism-of-action driven mandatory PIP and reorganization of incentives to a stepwise and incremental approach. Interim and final deliverables should be defined within a PIP or iPSP, each attracting a reward on completion. A crucial change would be the introduction of the interim deliverable requiring production of paediatric data that inform the go/no-go decisions on whether to take a drug forward to paediatric efficacy trials.

Conclusion: Additionally, to address the critical gap in the current framework where there is a complete lack of incentives to promote paediatric-specific cancer drug development, we propose the introduction of early rewards in the Orphan Regulation, with a variant on the US-Creating Hope Act and its priority review vouchers.

Keywords: drug development; incentives; paediatric oncology; paediatric regulation; supplementary protection certificate.

FIGURE 1

Current legal framework of incentives for paediatric drug development in the EU. Under the Paediatric Medicines Regulation, paediatric investigation plans (PIPs) are condition‐driven and follow drug discovery in adults. A reward can be obtained on delivery of a completed PIP and updated product labelling. Additional incentives can be achieved if the drug receives orphan designation. EMA, European Medicines Agency; MA, Marketing Authorization; ODR, Orphan Drug Regulation; PIP, Paediatric Investigation Plan; PMR, Paediatric Medicines Regulation

FIGURE 2

Proposal to accelerate paediatric drug development. Proposal 1 aims at driving earlier initiation of paediatric studies in a mechanism‐of‐action driven environment. Paediatric investigation plans (PIPs) should be considered as a more iterative process with defined interim and final deliverables, each attracting rewards in their own right (first and final rewards). EMA, European Medicines Agency; MA, Marketing Authorization; PIP, Paediatric Investigation Plan; PMR, Paediatric Medicines Regulation; SPC, Supplemental Protection Certificate

FIGURE 3

Proposal to incentivise paediatric‐specific drug development. Proposal 2 aims at providing incentives for drug development specifically directed at cancers occurring only in children. A new early reward would be granted right after a first marketing authorization for a paediatric cancer indication, warranting an immediate economic gain, as opposed to the classic late reward. This late reward would, however, remain as it is now. MA, Marketing Authorization