CDDF – ITCC – SIOPE 4th Paediatric Oncology Conference - Accelerating the development of new oncology drugs for children and adolescents
CDDF – ITCC – SIOPE 4th Paediatric Oncology Conference
Accelerating the development of new oncology drugs for children and adolescents
20-21st January 2016, Brussels, Belgium
James Calvert, Research Officer - Solving Kids' Cancer
The Cancer Drug Development Forum first held this conference in London in 2011 (under their previous name Biotherapy Development Association) with the title New Oncology Drug Development for Children and Adolescents in Europe: Current Status and where to go? Since then much work has gone in to creating a unique platform to facilitate interactions between all stakeholders to improve the efficiency of cancer drug development. Just from looking at the agenda in the lead up to the meeting it was clear that strides have been made in bringing together responses and ideas from all members of the field to form a coordinated effort to change the way paediatric drug development is regulated in Europe.
As a result of previous meetings a platform between four groups of stakeholders – academia, industry, regulatory groups and patient advocates – has formed. The aims of this platform include improving and speeding up paediatric oncology drug development; strengthening cooperation between stakeholders; and preparing for the 2017 review of the regulation. From this platform three working groups have been created:
Working group 1 – Focuses on defining a strategy for the implementation of mechanism of action, biology-driven drug development.
Working Group 2 – Aims to propose incentives to engage industry to develop paediatric drugs, based on a contextualised US model. Solving Kids’ Cancer has members who sit on this working group to help give a louder parent voice to the movement.
Working Group 3 – Is to produce a position paper on long-term follow up for children and adolescents receiving new anticancer drugs.
These working groups set the framework for the conference in Brussels, each lending their aims to a session surrounding these important topics.
Session 1: Accelerating Drug Development for Children with Life-Threatening Diseases
The first session of the meeting was kicked off by Gilles Vassal, President of SIOPE in France as well as the Chairman of ITCC, France. The presentation was an interesting round-up of the current regulatory landscape in Europe and noted that, while progress has certainly been made, there is still a long way to go to ensure children have access to the innovative therapy they need. Professor Vassal discussed the unjustified use of class waivers (of which 72% are in oncology) using the case of Crizotinib as an example as well as going over unjustified delays granted by the EMA. This set the tone for the rest of the meeting and highlighted the problems faced by parents and their children in the current regulation – and the things we as a group were to focus on.
Following an interesting presentation on the Unite2Cure movement, which aims to mobilise the public and shine a light on the debate surrounding drug prioritisation in paediatrics, came a very informative talk on the recent changed made by the PDCO (the paediatric committee of the EMA) by its chair, Dr Dirk Mentzer. For stakeholders at the meeting, an important take-home message from this presentation involved the recent review of the class waiver system by the PDCO (July 2015). This review recommended that the list of “adult-only” indications be significantly reduced but it still remains that waivers are granted based on the indications they intend to treat, not by their mechanism of action. A question was put forward using the example of Crizotinib – if it came through for a class waiver today, how much authority do the PDCO have to request a PIP? The answer was disappointing in that, legally, it is not possible to deny a waiver based on anything other than the intended indication.
The roundtable discussion that ended the session highlighted two points – that PREA (the FDA mandatory paediatric regulation) is to be changed within the next two years to assess their applications based on mode of action, and that the pharmaceutical industry needs to be incentivised to start paediatric drug development early as it involves a great deal of investment on their part for, potentially, little return.
Session 2: Prioritisation through Mechanism of Action – Why? How?
To start the second session Dr Andy Pearson, respected the world over, presented the findings of Working Group 1, whose objective is to develop a model of mechanism of action-driven (MoA) drug development. The working group came up with some key elements of the MoA approach, including the development of an aggregated, publicly available database of tumour targets in order to ensure the data is available for those assessing class waiver applications. This database would include incidence and prognostic relevance in individual malignancies as well as evidence supporting the strength of the target as a cancer driver (both at presentation and at relapse). A key message in this talk was that more research is needed to focus on biological markers and pathways in paediatric cancers in order that, should the regulation change to be MoA-focused, as many paediatric trials as possible would go ahead. That being said it was also recommended that waivers and deferrals be constantly reviewed on the presentation of new data surrounding tumour targets in children and adolescents.
An important issue was raised in the final presentation of this session – The safety of recruiting teenagers in adult early drug trials. This talk focused on the inclusion of adolescents (defined as between the onset of puberty and independence) in these trials, not all children. That being said it was interesting to hear that maximally tolerated doses of drugs in paediatrics averaged at over 90% of those seen in adults (some at 100%) and that toxicity profiles remained similar, independent of age. The problems with adolescent recruitment however include the often changing height and weight as well as the varying hormone levels.
Session 3: Long Term Follow Up of Patients Receiving Innovative Oncology Drugs
The last session of day one began with a talk by an inspiring childhood cancer survivor, now in his early 30s. He spoke about his experience and that of his friends in similar situations as well as discussing the need for strategic long term follow up in paediatric cancer care, well after what is currently being done in Europe.
This session brought together industry and academia to set out proposals for setting up a long term follow up programme. A representative of Novartis stressed the need of mandatory adverse event data collection on all post-authorisation studies involving long term follow up as well as the need for different types of study including active surveillance, observational studies, and clinical trials. Lars Hjorth, who works on follow up in Sweden, discussed the fragmented approach and the vast differences in care and regulation between countries in Europe and beyond. His proposal for a “survivorship passport” was most interesting, this would document all treatment received and all follow up which would be taken with the patient to ensure the best follow up care and the ability for healthcare providers to observe outcomes over time.
The proposals by working group 3 rounded off the first day. It was agreed that follow up is a lifetime activity and that funding challenges get in the way of developing successful programmes. It was also noted that there needs to be further clarity on the regulatory requirements to ensure patients and those in healthcare know what needs to be done to ensure the best care. Patient advocate groups made interesting points in that the transition from treatment to follow up care should be smooth and thorough as well as highlighting the need for the incorporation of preventative information to ensure the best outcomes.
Session 4: New Incentives for Specific Paediatric Oncology Drug Development
Day two commenced with an insightful talk by Florian Schmidt, of the European commission, who discussed rewards and incentives in paediatrics and how their impact is assessed. Notably, he mentioned the economic benefit of the six-month patent extension both in Europe and the USA (where it is only granted after voluntary paediatric trials after written request). He also presented the current state-of-play with regard to PIPs and mentioned while 841 PIPs have been agreed since coming into existence, only around 11% of these have been completed.
Following on came a great presentation by Nancy Goodman of Kids V Cancer, USA to set out the Creating Hope Act and explain how parent advocacy was a driving force behind getting the act passed into law. The Orphan Drug Regulation was then discussed from both an industry view and by Prof Vassal. The main points included its success, even in ultra-rare disease, but also its need to adapt. Adaptations suggested included bringing the incentives forward, potentially reducing risk (especially for smaller biotechs) and increasing the chance of investment from larger firms.
The session was ended with the presentation by Patricia Blanc on the proposals set out by Working Group 2 on potential new incentives for paediatric drug development. This was exciting for the Solving Kids’ Cancer team, having worked closely with WG2 in face-to-face meetings and on the proposal. The presentation outlined the segmented award approach, brought about by assessing the results of a survey sent out to industry and from a great deal of discussion between all stakeholders. The main point of this proposal was to bring about earlier incentives and to create a flexible, transferrable voucher (inspired by that in the USA) to make the development of paediatric drugs more commercially viable and attractive to the industry. Another aspect to the proposal involved the EMA’s PRIME initiative which aims to accelerate assessment and optimise the development of medicines of major public health interest. The idea of the working group is to gain recognition for certain paediatric cancers as eligible under PRIME (DIPG for example which has no curative therapy).
The Next Steps
Having presented the proposals from all working groups and discussed them with all stakeholders the next step is to involve policymakers and those who are experts in European law making to aid and advise on getting these changes put before the European Parliament.