Paediatric Drug Development: Is There a Way Forward?

At present, children and adolescents in Europe cannot access the innovative anticancer therapies developed for the treatment of adult cancers, and only a few paediatric cancer studies have been performed to effectively introduce new medicines for children into the market. While the need to develop more, safe and more effective anticancer medicines for paediatric use is today a matter of consensus, pharmaceutical companies so far fall behind in their studies, possibly as childhood cancers do not represent a broad enough market.

The 2007 European Union Paediatric Medicine Regulation was a step forward to incentivise industry to consider research and development of drugs in children, by requiring a Paediatric Investigation Plan (PIP) for any drug being developed for adults before a Marketing Authorisation is given by the European Medicines Agency (EMA) . However, the Regulation also allowed for exemptions from the obligation to submit a PIP upon specific waiver requests to be addressed to the EMA Paediatric Committee (PDCO). Waivers could be granted because the medicine was likely to be ineffective, unsafe, or not have a significant therapeutic benefit over existing treatments, or, importantly, intended to treat an illness that only occurs in adults. These rules on waivers were not generating enough, or the right, studies in children: indeed, only one new cancer drug for use in children has been approved since the Regulation came into effect.

In July 2015, the EMA PDCO revised the list of class waivers for medicines that are not required to submit a paediatric investigation plan (PIP). This revision marks a shift away from waivers that refer only to specific diseases which, says EMA, can mean overlooking the potential for the use of the medicines in children more generally. The revision thus aims to encourage companies to develop more new medicines for use in children, and the new rules are expected to come into effect only in 2018.

Following this important development, the article ‘Will the revised class waiver list make it?’, was published on the Lancet Oncology journal in September 2015. The paper has been co-written by several SIOPE partners in the framework of the CDDF-SIOPE-ITCC-ENCCA Paediatric Platform, created to intensify cooperation between all stakeholders: academia, parents and survivors, industry and regulators, as well as policymakers and charities. The article explains that medicines were unjustifiably exempted according to the previous list of waivers and acknowledges that, already in the past, both paediatric oncologists and parents had been calling for the PIPs implementation on the basis of the drug’s mechanism of action. Although congratulating PDCO for its extensive work, authors hypothesize that the impact of the revision on increasing the availability of drugs for children may be limited. Indeed, if a company decides to request a waiver on the old basis that the illness does not exist in children – even though the drug’s mechanism of action is relevant for paediatric malignancies – PDCO still cannot oblige the company to assess the drug in children.

Another development in the same field happened last November, when several patient groups including Unite2Cure and two influential Members of the European Parliament: Glenis Willmott (UK) and Françoise Grossetête (France), called for an immediate review of the EU Paediatric Medicine Regulation in a letter to the EU Health Commissioner Vytenis Andriukaitis. The letter intends to encourage research on paediatric cancers and underlines the urgency of a complete revision of the current legislation. Indeed, the letter argues, the Paediatric Medicine Regulation only had a limited impact on drug development and did not meet all expectations. Signatories make clear that the recent revision of the class waivers list is not enough, and that new incentives for pharmaceutical companies to study childhood diseases in the first place should be put in place.

In conclusion, although the revision of the class waiver list by the PDCO could be considered as a step in the right direction, the SIOPE community are concerned that it might not sufficiently reduce the number of medicines unjustifiably exempted from paediatric investigation. As we have emphasised before, the real change will come from considering the mechanism of action of a medicine, and setting up an efficient prioritisation process involving all stakeholders and more efficient obligations and incentives.

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