Regulatory changes have been enacted in the United States (US) and European Union (EU) to encourage the development of new treatments for pediatric cancer. Here, we review some of the factors that have hampered the development of pediatric cancer treatments and provide a comparison of the US and EU regulations implemented to address this clinical need. We then provide some recommendations for each stage of the oncology drug development pathway to help researchers maximize their chance of successful drug development while complying with regulations. A key recommendation is the engagement of key stakeholders such as regulatory authorities, pediatric oncologists, academic researchers, patient advocacy groups, and a Pediatric Expert Group early in the drug development process. During drug target selection, sponsors are encouraged to consult the Food and Drug Administration (FDA), European Medicines Agency (EMA), and the FDA target list, in addition to relevant US and European consortia that have been established to characterize and prioritize oncology drug targets. Sponsors also need to carefully consider the resourcing requirements for preclinical testing, which include ensuring appropriate access to the most relevant databases, clinical samples, and preclinical models (cell lines and animal models). During clinical development, sponsors can account for the pharmacodynamic (PD)/pharmacokinetic (PK) considerations specific to a pediatric population by developing pediatric formulations, selecting suitable PD endpoints, and employing sparse PK sampling or modeling/simulation of drug exposures where appropriate. Additional clinical considerations include the specific design of the clinical trial, the potential inclusion of children in adult trials, and the value of cooperative group trials.
In the last few decades, great progress has been made in developing new treatments for adult cancers. However, development of new treatments for childhood cancers has been much slower. To encourage drug companies (sponsors) to develop effective treatments for childhood cancer, authorities in the United States (US) and Europe have made new rules for drug development. Under these new rules, sponsors developing drugs for specific cancers in adults have to consider whether the target of that drug also causes cancers in children. If this is the case, sponsors have to carry out clinical studies of their drug in children who have cancer that is caused by the same drug target. In this article, we describe some reasons for why drug development for childhood cancers has been slow and the rules created to address this problem in the US and Europe. We share some recommendations to help sponsors maximize their chances of developing an effective drug in children while satisfying the new rules. Specifically, sponsors need to be aware of the differences between studying drugs in adults versus children and how these influence the way the drug is tested. We make several recommendations for each stage of the development process, beginning with what is needed even before human studies begin. Finally, we highlight some issues that sponsors need to think about during drug development, from the preclinical stage (testing drugs in cells and animals) through to clinical testing in adults and pediatric patients with cancer.
© 2021. The Author(s).