Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Comparison of the EU and US paediatric legislations and critical analysis of the expected impact of the FDA’s "RACE for Children Act" on the development of paediatric cancer medicines ***

Dr. Maria Huthmacher (geb. Schacker) (Abschlußjahr: 2022)

Summary
Language: English
Historically, studies evaluating medicinal products in the paediatric population have been rare. This has led to extensive off-label use in this population, which bears significant risks for serious harm. While paediatric legislations in both Europe and the US have improved the overall situation, there still is a long way to go. In particular, certain therapeutic areas such as paediatric oncology are lagging behind and there is an extremely high medical need to develop safe and efficacious medicines for the treatment of paediatric cancers. Although there are differences between adult and paediatric cancers, such as in the aetiology, genetics, organ of origin or natural history of the disease, the genetic drivers and molecular abnormalities underlying adult cancers are also found in many paediatric cancers. Thus, products being developed for the treatment of adult cancers may also have a very high potential for the treatment of paediatric cancers.
In the US, the RACE for Children Act was introduced and came into effect in August 2020. The FDA now has the opportunity to demand the evaluation of new drugs or biologics in a paediatric oncology indication in case the product is intended for the treatment of an adult cancer, and the molecular target of the product is considered substantially relevant to the growth or progression of paediatric malignancies.
This thesis evaluated the expected effect of the RACE for Children Act on the development of paediatric cancer medicines.
The evaluation shows that the RACE for Children Act has indeed a lot of potential to significantly improve the situation for paediatric cancer patients in the US. There is a big gap between actually available paediatric cancer treatments and potentially efficacious medicinal products which are available or being developed for adults. Until recently, the majority of these products were excluded from the PREA requirements to submit a PSP either due to the PREA orphan exemption or because the adult indication does not occur in the paediatric population, and were thus only developed for adult cancer patients. Under the RACE for Children Act, however, Sponsors now also need to consider their potential for paediatric patients in a much broader context. It can thus be expected that many more medicinal products will also be developed for the treatment of paediatric cancers in the future. A comparison with the situation in the EU and the number of agreed PIPs in the oncology field further highlights this potential.
In addition, a comparison with the effects following the EU class waiver update in 2015 was performed, as this had the same purpose as the RACE for Children Act, i.e. to increase the number of paediatric oncology treatments. These data further indicate that the RACE for Children Act in the US will likely be very effective. In fact, it may even be more effective than the class waiver update due to the fact that the sole driver will be the product’s mechanism of action so that oncology PSPs in the US are no longer restricted by their adult indication unlike EU PIPs where the adult indication is also taken into account to some extent.
Finally, oncology products approved by FDA between August 2020 and December 2021 and falling under the RACE for Children Act were examined to investigate whether the assessments and predictions of the first two steps hold true for this preliminary dataset. While conclusive assessments can certainly not be drawn from this small dataset, there is a clear trend for an increase in number of PSPs, which supports the evaluations and assessments of this thesis.
Nevertheless, several issues connected with the development of paediatric medicinal products in general will remain, such as limited availability of a sufficient number of eligible patients as well as lack of experienced investigators and clinical study sites. While these can potentially be limited by smart trial designs and use of modelling/extrapolation concepts, or the use of RWE wherever possible, it remains to be seen how open both Sponsors and regulators are and continue to be to such approaches.
Overall, however, it can be concluded that in the long-run the RACE for Children Act is expected to be a milestone for the development of safe and efficacious treatment options for paediatric cancer patients.
Pages: 59
Annexes: 3, Pages: 37