Adult oncology drug development is currently expanding beyond well-studied areas to target the patient’s immune system, unique genetic profile and metabolism. These innovative oncology drugs can be more effective than traditional drugs in several refractory malignancies, and recent research breakthroughs showed the important connections between paediatric and adult cancers in terms of underlying molecular biology. In spite of this, and the fact that cancer is the first cause of death by disease for children beyond the age of one, investment for paediatric oncology drug development lags far behind that for adults. Speeding up the introduction of safe and innovative treatments into standard cancer care for children and adolescents is a priority for SIOPE: “innovative treatments” is indeed one of the 7 key objectives of the SIOPE Strategic Plan. Via this reference document for the years to come, SIOPE and its partners aim to address the current challenges and lack of clinical trials of innovative oncology drugs for children. better access to innovative therapies can save the lives of children and adolescents with cancer, and there could be ways to accelerate drug development for the paediatric population; for instance, the way a specific drug compound works (its “Mechanism of Action”, MoA) in an adult type of cancer may be relevant to a malignant type that only occurs in children. However, trial sponsors at present do not consider its potential benefit for the paediatric ones, while waiting for the drug to show promise in adult patients. Moreover, pharmaceutical companies considerably rely on the possible derogations to the legal requirements for paediatric drug development, e.g. as the treatment being researched is for a disease which does not occur in children, or vice versa. Several drugs potentially beneficial for a paediatric malignancy have been thus unjustifiably waived. When eventually mandated, Paediatric Investigation Plans (PIPs) often prove unfeasible because they focus on the rare occurrence of an adult cancer in a child rather than the potentially wider use of the new drug in other relevant childhood cancers. Finally, financial incentives to develop drugs for a cancer which only occurs in childhood often come too late for pharmaceutical companies to consider investing in research. Following the conclusions of the last CDDF-ITCC-SIOPE Paediatric Oncology conference (20-21 January 2016, Brussels) SIOPE and the parent associations’ network “Unite2Cure” decided therefore to join their forces and propose some changes to the 2007 EU Paediatric Medicines Regulation. This important piece of legislation, which concerns all areas of paediatrics and did improve the landscape of paediatric drug development in the past ten years, fails however to address the oncologic needs of children and adolescents: less than 10% of children in relapse with a terminal cancer have access to new, experimental drugs from which they could benefit. There is a need to learn from the past, and a few updates in the EU Regulation could harness the major advances that have been made in biological science to facilitate a quicker and prioritised development of paediatric medicinal products. This is why SIOPE and its partners suggested the following 4 proposed changes:
- Paediatric investigation of drugs based on ‘mechanism of action’ rather than adult disease: current PIPs include a product-specific waiver for oncology products, and if the drug intended for an adult condition is in the EMA class waiver list the company can avoid to develop the agents in the paediatric population. However, SIOPE and its partners think that the decision to agree/waive the paediatric development of a medicinal product should not be based on its indication in adults but on the evaluation of its potential therapeutic benefit (including the relevance of its MoA) over existing treatments in the paediatric population. This evaluation needs to be accurate, detailed and clear, including paediatric biological and preclinical data in relation to the drug mechanism of action, and even preliminary clinical data in the paediatric population;
- Prioritisation of drugs in order to match the best available therapies to children with rare/refractory malignancies: there is an inventory of the therapeutic needs of the paediatric population in the current Regulation, which identifies the existing medicinal products currently used and highlights the therapeutic needs and the priorities for research and development in this population. However, this inventory is not listing the needs on the basis of the diseases children are suffering from, but it is a list of the additional information needed to improve the use of already marketed drugs (safer and better evaluated) in the paediatric population. This does not allow companies to easily identify opportunities for business development, and there is therefore a need for a new process that will prioritise compounds to be developed for children when i) several drugs in the same class, or with similar MoA, are developed for adults or ii) several drugs with different MoA have a potential therapeutic benefit in the treatment of a disease occurring rarely in children. The “prioritisation mechanisms” suggested by SIOPE and its partners would share available information and best inform further decisions in this field;
- Reduction in the delays in starting the paediatric development of potentially life-saving innovative drugs: although the Regulation states that PIPs have to be submitted early during product development in adults, in order to address the therapeutic needs of the paediatric population in good time, nearly 95% of oncology PIPs have been submitted late in the drug development process and often have deferrals. This is why it has been suggested to consider some penalties when a company submits a PIP or a waiver after the planned deadlines, in order to incentivise timely submission and implementation of development plans. This would also increase the existing research cooperation between pharmaceutical companies and academic groups;
- More effective and flexible rewards to better incentivise the development of new and specific paediatric medicines: as the biology and physiology of several childhood cancers are specific to the paediatric population, no specific provision in the current Regulation aims to incentivise the development of innovative medicines that would turn into medicinal products specifically aiming at treating severe paediatric conditions such as cancer. In order to encourage a first marketing authorisation for a drug intended to specifically treat such conditions, SIOPE and Unite2Cure suggest the implementation of incentives that are transferable in the form of an extension of patent, a supplementary protection certificate, or a voucher to accelerate the introduction of another medicinal product into the market.