In May, the Unite2Cure team headed to Brussels to meet with the Health Commisioner Vytenis Andriukaitis. Patricia Blanc, Chris Copland, and Anne Goeres, our delegates from Unite2cure informed the Health Commissioner as to the importance of the Paediatric Regulation, explained where problems have been identified with this regulation in relation to childhood cancer and why change is necessary .
UNITE2CURE at the European Commission to meet with Health Commisioner Vytenis Andriukaitis: Changes are needed to the Pediatric Medecine Regulation
An excellent three-day event in Belgrade organized by Childhood Cancer International (CCI) Europe ended on a positive and motivated note for the several Unite2Cure members who attended. The general mood was that the message had been understood: the time for action is now!
The Unite2Cure movement was presented in a one hour interactive session by Chris Copland, Anne Goeres and Nicole Scobie.
“We wanted them to really hear what we were saying, really understand the message.” explains Nicole Scobie, from Zoé4life, Switzerland. “It was an early morning session after a late night out the evening before, and we knew people would be tired. We felt if we started out with a long power point on this difficult subject (paediatric medicines regulations), we would lose the audience. We decided to use humour and small working groups to get people talking and thinking about these issues.”
“Not everyone in the audience is a native English speaker,” adds Anne Goeres, from Fondatioun Kriibskrank Kanner, Luxembourg. “We realized that we needed to make sure we used simple, clear terms that everyone could understand.”
When Chris Copland, a teacher from the UK and Unite2Cure founding member began talking to the attentive audience about “loopholes” in the law, Anne quickly broke in to point out that she did not know this term. Chris was ready with his cable, to actually build a real “loophole” and show everyone how there is a hole in the law which allows pharmaceutical companies to avoid their obligations regarding child cancer.
Although the presentation was deliberately entertaining, the message was crystal clear: we must take action now if we are to have our voice heard. The review of the Paediatric Medicines Regulation is due in 2017 – this means we must act now.
Anne, Chris and Nicole ended their presentation with a call for action:
-become a Unite2Cure ambassador in your country
-mobilize your MEP and your minister of Health
-sign a “golden letter” to the commissioner of Health to the European Union.
The golden letters had been prepared ahead of time, with a space for each participant to add in his or her own message within Unite2Cure’s call for change to the PMR. Each letter was then sealed in a golden envelope, which were collected and will be presented to the Commissioner at Unite2Cure’s meeting with him in May.
If you would like to send a “golden letter”, please click here, download the letter, fill in your information, and email it to: email@example.com
If you would like more information on becoming a Unite2Cure ambassador in your country, or in supporting the movement, send us an email at firstname.lastname@example.org
There have been many incredible advances in the treatment of adult cancers in the past 10 years, but childhood cancer is losing out for many reasons, including the opportunity for industry to apply for waivers in the drug development process. Investigating new agents in children and adolescents is particularly difficult as their numbers are few, studies are costly and outcomes are not guaranteed. This leads to long delays for companies who answer to shareholders, and so sadly a waiver to avoid having to test efficacy in children is the attractive option for many. The bottom line is that children are often sidestepped in the drug development process because of financial challenges.
It is a well-known fact that most children diagnosed with cancer are treated with chemotherapy drugs which are over 30 years old. If we continue to do this, then current survival rates for the most resistant cancers are unlikely to change, the prospect for cure at relapse remains low, and the toxicities (both acute and long-term) will remain unchanged. By ignoring these issues, we are failing our children. Cancer is the number one cause for death by disease in children and adolescents, but in the adult world it is no longer recognised as the automatic death sentence that it once was. Childhood cancer is genetically a much simpler disease, with lower molecular mutation rates. Children and adolescents also have substantially less co-morbidities given that they have exposed their bodies to fewer toxins in their short lives. All these elements point towards the fact that childhood cancer should be addressed in a much more positive and productive way, which is likely to lead to much greater curative rates than are currently being achieved.
Developing new drugs specifically for children will address many of these issues, but another key element to consider is prioritisation. Although 35,000 children and adolescents are diagnosed with cancer each year in Europe, when this number is attributed to individual diseases and disease sub-categories, the numbers of children and young people in each classification are few. This makes prioritising drug development another key issue, as only the most promising compounds and technologies should be brought to the fore for testing when it comes to these very small populations. Children are precious, and should be treated as such in every regard, including childhood cancer research.
Many parents and charity advocates are extremely knowledgeable on this topic, and have spent years campaigning to bring these issues to light. Unite2Cure is uniting these highly informed people and groups to gather momentum to bring one voice to the European Commission in asking for change to regulation to address these core issues. We recognise that difficulties exist for other stakeholders, but we believe many of these can be overcome by making small but strategic changes to the European Paediatric Medicines Regulation.
Parents who have lost their children to cancer, parents who live in fear of relapse and nurse their children through long term side effects, and charities supporting these desperate families all recognise the need for change and see an opportunity for it to happen. Academics understand the limitations of the current regulation and research landscape. Paediatric oncologists state that they don’t want to be the generation who simply administered drugs to maintain this current curative plateau. Surely those highly skilled, highly paid individuals working within drug development grasp these issues and are keen to change the future of many children diagnosed with this devastating disease?
If only it was considered a good return on investment, then this might be the case.
Show your support by signing our petition.
Leona Knox, Unite2Cure
The Unite2Cure team has composed the following letter, which has been sent to Mr. Andriukaitis, Health and Food Safety Commissioner, European Commission.
Dear Mr Andriukaitis,
We are writing regarding your reply to the letter (dated 10 November) in which MEPs Glenis Wilmott and Françoise Grossetête, draw attention to the failure of European legislation to address the needs of children with cancer.
We appreciate the time you took to review this issue but we strongly feel the need to respond to some of your comments, which in our view do not paint a realistic picture of childhood cancer drug development and, above all, fail to recognize the urgent needs of these young patients.
We all know that the development of new drugs, not just anti-cancer drugs, is a very challenging and risky endeavor and that, ultimately, it is dependent on research and development efforts that cannot be dependent upon legislative measures. We are also well aware that there are legislative tools, such as Orphan Drug legislation and the Paediatric Medicine Regulation that seek to promote, in one way or another, the development of new medicines for children. The point that should be clear by now is that these measures have a limited impact on childhood cancer drug development and this is the specific problem we would like to address. Just looking at the big picture without analyzing the details will not lead us anywhere.
Orphan drug incentives have been around since the early 80s in the US and were introduced a little later in Europe. It is now crystal clear that these incentives are not powerful enough to stimulate the development of new drugs for childhood cancer. If we look at the US experience, where more solid drug approval records are available, we see that over the past 20 years a total of 180 drugs were approved for the treatment of cancer in adults. During the same time only 3 were approved specifically to treat cancer in children. The record within the EU is even more dismal.
The current incentives provided by Orphan Drug Legislation are sufficiently powerful to support development of drugs for other rare conditions in children. However, for scientific and financial reasons, they fail to meet the needs of childhood cancer. These are very complex diseases to tackle and oncology drug development has on average the highest failure rate. On the other hand, rare genetic diseases are often more treatable because the pathology is driven by one or very few specific genetic drivers. This makes drug development relatively less risky. In economic terms, the tendency of these diseases to become chronic when treated increases the revenue potential of any new drug, which is also likely to be prescribed at a premium price. This financial return is harder to achieve with a paediatric cancer drug as the treatment times are generally shorter and the drugs are unlikely to qualify for premium price, particularly if the same drug is used in more common, adult cancers.
If the Orphan Drug Legislation incentives do not work for childhood cancer drug development, it is equally clear by now that the obligations and incentives envisaged in the Paediatric Medicine Regulation (PMR) do not work either and do not have any meaningful impact on the development of new drugs for children with cancer. Whereas the PMR has indeed stimulated an increase in R&D investment in many paediatric areas, it has failed to make an impact on childhood cancer.
This is not a matter of parental opinion. This is the unanimous conclusion of all key paediatric oncology stakeholders in the 2012 five-year review of the PMR and it is a conclusion that is supported by the very same data you produced to demonstrate impact of this legislation.
Let us be more specific.
As pointed out by Ms Wilmott and Ms Grossetête, up to 6000 children and adolescents die of cancer every year in Europe. We have made some progress in the treatment of certain cancers such as some forms of blood cancers (e.g. lymphomas, leukaemia). However, in a number of high risk cancers that are very specific to children and adolescents (cancers such as neuroblastoma, bone cancers such as Ewing’s Sarcoma and aggressive brain cancers in general), we have not seen any significant therapeutic improvement over the past two decades. These are diseases that take the biggest toll in terms of young patients’ lives on a yearly basis. These are the diseases for which new drug development is the most urgently needed.
Yet, these cancers are largely neglected by industry. In addition, the current legislation allows for waivers even when the science suggests a potential use of certain investigational drugs in specific childhood cancers on the basis of a common mechanism of action. In other words, we are missing opportunities to study compounds that may bring benefit to patients.
You quote some figures provided by EMA experts. The problem with this is that these are just numbers if they are not interpreted and analysed in the right context. You rightly state that more than 80 paediatric investigation plans (PIPs) have been agreed by the EMA Paediatric Committee. The exact number is actually 81 on the EMA website (accessed Jan 5, 2016 ). Actually only 10 of these positive decisions targeted at least one of those high risk cancers that primarily affect children, a mere 12% of the total study number.
It is true that a number of studies (16) involved haematological malignancies that do indeed frequently occur in children with cancer but for these diseases we generally already have some valid therapeutic alternatives, unlike for the above mentioned solid cancers. Furthermore, to put things in perspective, the biggest group (17 studies) is made up of studies that do not target cancer but, rather, side effects such as nausea, vomiting, anemia etc. When you consider these details the overall impact is less impressive.
Therefore, it is fair to say that these studies largely fail to address the most urgent need for the paediatric oncology community, which is the development of new drugs for the most aggressive cancers, those which cause the highest number of deaths among children and adolescents.
You mentioned that 5 drugs with a paediatric indication have been approved for children since the PMR was implemented, drawing the conclusion that it is very likely that these programmes would not have been conducted without the PMR. It is not clear which drugs you are referring to but, in any case, we would argue that the data does not support your conclusion.
As far as we know, 9 anti-cancer drugs have been approved for paediatric use since 2007. These are the following (target disease and date of EMA approval in brackets):
nelarabine (2007) *
imatinib (CML, 2009) * A
mifamurtide (OS, 2009) *
mercaptopurine (ALL, 2009) *
everolimus (SEGA, 2011) PIP # A
mercaptopurine (ALL, 2012) * F
imatinib (ALL, 2013) PIP A
dinutuximab (NBL, 2015) PIP
asparaginase (ALL, 2015) PIP
* = did not fall under paediatric regulation (e.g. before regulation came into force or well-established use)
# = anti-neoplastic medicine (concerned neoplasm is not a cancer)
+ = nationally authorised in certain Member States
F = new paediatric pharmaceutical form
PIP = based on studies in an agreed PIP
A = paediatric use was granted only after authorisation was granted for adult use
As shown by the above, only a few of these drugs can claim to be the direct result of the PMR. With the exception of Dinutuximab, none of the drugs above have been specifically developed to treat a form of childhood cancer.
We do not see how the data above can support the conclusion that the PMR has had any significant impact on childhood cancer drug development. The figures become also less impressive when taken in the context of global oncology drug development in general. It is estimated that every year approximately 100 to 150 new investigational drugs begin clinical testing and that any point in time there are up to 800-900 anti-cancer compounds in clinical evaluation. It is clear that not enough drugs are developed for children and adolescents. In our view, the approval record of paediatric cancer drugs suggests that this is just “baseline” activity of industry completely unaffected by the current legislation.
The EMA figures clearly show that, basically, no drugs are being developed for the high risk childhood cancers and that companies tend to delay paediatric development as much as possible, as it is regarded as a hurdle on the path of adult development. As you rightly note, the legislation is intended to encourage the development of drugs for children without delaying adult development. However, it was concluded in the 5 year –review published in 2013 that there is no evidence of a slowdown in adult drug development. On the other hand, the negative impact of waivers and deferrals on patients’ lives should not be underestimated.
While it is important to recognize that sometime a delay is indeed recommended in order to evaluate product safety in adults, we must also understand that whenever the paediatric development of a drug is waived or deferred for whatever reasons, there might be a heavy price to pay in terms of missed opportunities for patients. There have been examples of drugs that have been initially granted waivers or had paediatric development delayed only to recognize a few years down the line that the compound is highly beneficial to children. The targeted drug Imatinib was first approved for adults in 2001 for the treatment of a specific genetic subtype of chronic myeloid leukaemia (CML) and later for acute lymphoblastic leukaemia (ALL). The same drug was not approved for the treatment of ALL in children before 2013. Meanwhile, academic sponsored-trials in the US demonstrated a dramatic effect resulting in greatly enhanced survival rates, from 35% up to approximately 80%l. Surely we don’t need to explain that many more children could have been cured had the drug been made available earlier.
The implications of all these facts and figures are very clear.
We may have different views on how to reform the PMR and to what extent we may want to enforce stricter obligations and/or offer more attractive incentives. But one point should be clear by now. The PMR, as it stands, does not address the needs of children and adolescents with cancer. All key stakeholders and key opinion leaders agree upon this point. This was the conclusion of the Europe Society of Paediatric Oncology (SIOPE) in 2012 after the first review of the PMR requested by EMA. This is opinion of countless patients/parents’ organisations united under the Unite2Cure umbrella. If we simply acknowledge the problem we can start to have a sensible and constructive discussion with all stakeholders, with the probability of enacting reforms that will make sense for all parties.
If, by contrast, we do not acknowledge this fact and insist we need more time to judge, we are, indirectly, harming all those young patients that will be diagnosed with cancer in the near future. Time is exactly what children and adolescents with cancer do not have.
Those of us whose children have been and are being impacted by cancer know first-hand the urgent need to tackle the disease which causes the highest number of deaths amongst our children in Europe. We want our political representatives and European legislators to recognize this need for urgency and to facilitate changes that will give children diagnosed with cancer a better chance of life.
As Ms Wilmott and Ms Grossetête clearly wrote, the time for action is NOW.
We very much look forward to your thoughts and comments.
The Unite2Cure Team
Nicole Scobie, Zoé4life (Switzerland)
Debbie Binner, Create for Chloe and trustee of aPODD (UK)
Patricia Blanc, Imagine for Margo children without cancer (France)
Anne Goeres, Fondatioun Kriibskrank Kanner (Luxembourg)
Danielle Horton Taylor, PORT and Consumer Representative National Cancer Research Institute (UK)
Anita Kienesberger, Österreichische Kinder-Krebs-Hilfe (Austria)
Angela Polanco, Bethany’s Wish (UK)
Cesare Spadoni, aPODD (UK)
Chris Copland, Consumer Representative, National Cancer Research Institute (UK)
Gerlind Bode, Board Member of Förderkreis Bonn e.V. (Germany)
Kevin and Karen Capel, Christopher’s Smile (UK)
 EMA Officer – Personal Communication
A guest blog by Katharine Wright,Nuffield Council on Bioethics
Back in 2013, the UK-based Nuffield Council on Bioethics set up a working party to look at the ethical issues arising out of children’s involvement in clinical research. The working party’s subsequent report, drawing on the contributions of over 500 children and young people, parents and professionals, was published in May 2015, and its recommendations are made accessible in both a magazine format and as an animation.
The working party tackled not only the thorny issue of how children and young people can ethically be recruited to research, but also the more hidden ethical challenges that arise in connection with the ways in which research is prioritised and developed in the first place. We started from the premise that ‘good’ research (a shorthand for ethically robust and well-designed research that asks questions that are important for the health of children) should be seen as intrinsically good, and as a natural and necessary part of any healthcare system. Building on this point, we made the strong claim that it is not an ethically neutral act to say ‘no’ to research proposals that meet these requirements and might potentially lead to better health care for children. There is similarly a strong ethical imperative actively to promote such research – and as Unite2Cure highlights, the European Paediatric Regulation which mandates the inclusion of children and young people in clinical trials, unless a waiver has been granted, has a critical role to play in this arena.
The working party felt that the European Medicines Agency and the Paediatric Committee (the European institutions responsible for implementing the Regulation) should be commended for the very positive and proactive approach they have taken to their regulatory role. They have used it not only simply to police the system established by the Regulation, but have also sought actively to promote effective, collaborative, research with children and young people through a variety of practical means.
Nevertheless, much more can and should still be done – and our report picked out in particular the class waiver system, whereby medicines targeting ‘adult-only’ conditions have been exempt from the requirement to include children and young people in trials. We argued that this system was clearly not working as originally intended and strongly urged the Paediatric Committee (PDCO) to complete its promised review of the class waiver system as quickly as possible. In particular, we argued that PDCO should ensure that where the ‘mechanism of action’ of a medicine is potentially relevant to children (for example for a different illness from that targeted in adults), research with children should go ahead – a recommendation echoed in Unite2Cure’s proposals for improving research and care for children with cancer.
We therefore regarded PDCO’s announcement in July 2015 that they had revised the class waiver list, revoking eight such waivers, and updating fifteen more, as a “welcome step towards further promoting research with children”. This means that there are now fewer conditions where companies developing new medicines are automatically exempted from any requirement to develop a ‘paediatric implementation plan’ (PIP) setting out how they will involve children and young people in the study. However, under the Regulation, they are still potentially entitled to apply to PDCO on a case-by-case basis, and apply for a product-specific waiver, on the grounds that the condition being targeted by the trial medication does not arise in children. Thus, while PDCO will now be directly involved in discussing such cases with companies, they still cannot actually require them to produce a PIP – unless and until the Regulation is changed to give PDCO these powers.
The ‘ten-year review’ of the 2006 Regulation is coming up soon, offering a perfect opportunity to review the thinking behind the waiver system, and to ensure that PDCO has the powers it needs. We have written to the European Commission to urge the ethical imperative of such a change. In the meantime we urge all sponsors of research to consider the potential benefits of their research to children’s health – and where appropriate to include children and young people in trials on a voluntary basis.
Unite2Cure is delighted to be a partner in a multi-stakeholder call for concrete action to improve the availability of effective innovative cancer medicines for children and adolescents with cancer. The call was launched at the event ‘Development of Paediatric Cancer Medicines – Speeding up Innovation, Saving Lives’. Although cancer remains the first cause of death by disease beyond one year of age; very few new medicines reach children and adolescents with cancer in Europe, even after the implementation of the 2007 EU Paediatric Medicine Regulation.
The proposals were presented at a yearly event by The European Society for Paediactric Oncology (SIOPE) www.siope.eu/activities to mark International Childhood Cancer Day (15th February 2016). The aim of the proposals is to suggest solutions to the current lack of drug development for children and teenagers with cancer.
We are proud that Christopher Copland (UK), one of the founding members of Unite2Cure, spoke at the event of the urgent need to accelerate drug development for these young people. He called for more attractive rewards for the pharmaceutical industry to develop innovative drugs for children’s malignancies; following the example of the “Creating Hope Act” system in the USA.
Also there was Unite2Cure partner Anne Goeres (Lu) from the Foundation Kriibskrank Kanner. She stressed the need to join forces with the rare diseases’ community in advocating better treatments.
Member of the European Parliament Glenis Willmott (S&D, UK), a strenuous supporter of the causes of the childhood cancer community over the past years, hosted and introduced the event. Martin Schrappe (DE), President of SIOPE, presented the ‘SIOPE-ITCC-CDDF Multistakeholder Platform’, created in 2013 by representatives of parent/patient advocates, academia, industry and regulators. The Platform works on proposals to increase innovative drug development that are regularly presented to decision-makers during a series of Paediatric Oncology Conferences, the last of which led to three stakeholders’ joint proposals to improve the effectiveness of the Regulation’s implementation.
Unite2Cure is a parent-led movement which aims to mobilise the parent/child/NGO voice to push urgently for better treatments and better access to treatments for young people with cancer. The current status quo means that:
– 6,000 children and teenagers die of cancer in Europe each year
– less than 1 in 10 of children with relapsed terminal cancer has access to innovative new treatments.
– whilst progress has been made; many high risk cancers have not seen any therapeutic improvements in the past two decades
– childhood/teen cancers are largely neglected by industry
– current legislation allows waivers; even when science suggests a potential use
– EMA figures show that basically no drugs are developed for the high risk cancers.
If you care – join our discussion; sign our petition, or talk to us email@example.com or firstname.lastname@example.org
Last week several parents, survivors and patient advocates from Europe and the U.S. united in Brussels for the CDDF-ITCC-SIOPE 4th Paediatric Oncology Conference. The title of this year’s meeting was: Accelerating the Development of New Oncology Drugs for Children and Adolescents.
Debbie Binner of Create for Chloë presented the Unite2Cure movement along with Chris Copland, Consumer Representative, National Cancer Research Institute and Nicole Scobie of Zoé4life. The presentation was very well received, and as Debbie explained later, the conference ended with a general sense of possibility. “Believe me the first CDDF conference was very very different to this one. Us parents were fighting to be heard – and now there is such a sense of integration and collaboration and a real sense that we are making some progress. Although obviously there is a long long way to go.”
A few key moments:
Patricia Blanc of Imagine for Margo‘s presentation on new incentives for pharmaceutical companies to invest in paediatric research was brilliant. Her voice is powerful and the work of her Working Group on this project has moved forward with an action plan. Nancy Goodman of KidsVCancer gave an excellent and comprehensive update on the successful US Creating Hope Act regulation.
Angela Polanco of Bethany’s Wish participated actively in a round table discussion on the new incentives topic, and explained that parents want to be involved from the very beginning in the process of approving paediatric investigation plans and participating in the development of clinical trials.
Chris Copland spoke up several times, passionately advocating for change to the Paediatric Medicines Regulation. He and Anne will be speaking on behalf of Unite2Cure today, January 27th in front of the European Parliament at an event organized by SIOPE in honour of International Childhood Cancer Awareness Day. This influential awareness raising meeting entitled ‘Speeding up Innovation, Saving Lives’ will be hosted by MEP Ms Glenis Willmott. The goal is to address the development of paediatric cancer medicines and an enabling legislative and regulatory environment. In plain words: we are asking for very specific changes to the regulations NOW.
Leona Knox, of Solving Kids Cancer-Europe spoke with a powerful message, summarizing her feelings about the 2 day conference. “I am one of the parents here who won’t be going home to my son tonight. Oscar died, not because he had cancer, but because he ran out of treatment options. We parents have come here on our own time, and have worked so hard to make sure we understand what you have presented.” She told the audience of mostly pharmaceutical company representatives, pediatric oncologists and regulators. “Our goal is to save kids’ lives. We are working so hard to come up with solutions, and I just want to ask you all, to please help us fix this, whatever it takes.”
Both Samantha Schoolar of Bethany’s Wish and Jaap den Hartogh of VOKK spoke very clearly about the long term side effects survivors of childhood cancer experience and the need to speed up better treatments as well as research into late effects. “A real cure means being part of society once more,” explained Jaap, who called for new, better, and less toxic medicines as well as access to long-term follow up care for every survivor in Europe.
It was inspiring to hear Peter Adamson, the Chair of the Children’s Oncology Group stand up to remind the audience that the title of this conference was “Accelerating the Development of New Oncology Drugs for Children and Adolescents”, and that, having attended these conferences for the past several years, he did not want to just have the same conversations as every year. It was time to actually accelerate.
Gilles Vassal, past president of SIOPE and Director of Clinical and Translational Research at the Institut de Cancérologie Gustave-Roussy made a clear call to “change the mindset“.
The summary of the decisions and plans as a result of the conference are, briefly:
-a strengthening of the CDDF-ENCCA – ITCC-SIOPE platform with terms of reference, a website and a new name (to be announced!).
-position papers will be created by Working Group 1 on the issues of adolescent inclusion in adult phase one trials and on mechanism of action as a determinant for paediatric investigation plan requirements.
-a position paper is being drafted on Working Group 2’s proposals for new incentives
-a white paper will be put together by Working Group 3 regarding long term follow up for children receiving new drugs. This group met immediately after the conference to continue preparing this document.
Gilles Vassal emphasized that parents and survivors must continue to advocate for change for all of these plans to happen.
He ended the conference with one sentence, that summarizes the event, “We are even stronger if we work together.”
Chris heads to the headquarters of the European Medicines Agency on behalf of Unite2Cure…
The brash banking centre of Canary Wharf, with its gleaming sky-high towers, is the unlikely location for the headquarters of that most decorous of institutions, the European Medicines Agency. Standing between the murky waters of the Thames and Barclays HQ, the EMA gleams like a beacon for health rather than wealth, right in the heart of London’s bonus-driven business district.
The business I was to witness there, though, was of an altogether different kind.
On November 23rd, Unite2Cure posted an article entitled We need to move the lines, which was our message to the European Commission. Written by Chris Copland on behalf of Unite2Cure, the letter was addressed to Ms Juelicher, who is Head of Unit, Medicinal Products – Authorisations, European Medicines Agency, as well as to Commissioner Andriukaitis, Commissioner for Health and Food Safety, European Commission.
In it we describe how we found the Commission’s position, that the concerns raised by Mrs Wilmott and Mme Grossetete during the ‘Exchange of Views with the European Commission and EMA on the Policy on the Conditions for a Paediatric Investigation Plan/Waiver.’ on November 10, should be put aside until 2017, a sadly complacent one.
On December 17th we received a reply. Unfortunately, it does not address our concerns but is simply a copy of a letter sent to Mrs Wilmott and Mme Grossetete. We are disappointed in this response.
We have replied to their letter as follows and hope to hear more soon.
Dear Ms Julicher
Thank you for your response to our message. We were, however, disappointed that you simply referred to your open letter to Ms Wilmott, MEP and did not provide us with a direct reply. Although the letter was on associated themes, it did not address specific points we had made, for example about orphan illnesses. We, however, would like to respond here to the points you made, in particular your assessment of whether the Paediatric Regulation is functioning as effectively as it might.
As you point out, what makes the Paediatric Regulation different is that it does not just offer incentives, it places a requirement on companies to conduct studies into children. The effectiveness of this approach has been demonstrated in recent years but, unfortunately, it has not achieved its potential with regard to the most deadly of young people’s illnesses cancer.
You assert that the Regulation allows companies to propose paediatric plans for cancer on their own initiative, and it is true that on occasion this has happened. However, the track record, over decades, of companies voluntarily engaging with paediatric research is not an encouraging one (see Raymond and Herold). On the other hand, their willingness to avoid requirements by resorting to the loophole of the waiver system has been clearly demonstrated. As has been frequently related, during the first five years of the Regulation, over half of the adult drugs with a significant potential for children’s cancers had waivers requested and granted (see Vassal below).
You paint a positive picture by referring to the recent statistics supplied to you by the EMA. As we have not seen this data, we cannot respond to your interpretation in detail. However, we note that you place emphasis on the number of programmes that ‘target a condition where most patients are in the paediatric age range.’ You do not clarify whether, in these cases, a PIP has proceeded because there is a common condition for both adult and child or because companies have simply opted not to apply for a waiver. Either way, this ignores the simple fact that ‘’PDCO has to grant a waiver if the disease only occurs in adults.’ (EMA)
This is the central weakness of the legislation with regard to cancer, a disease which manifests itself differently in adults and children but still derives from a common biology. As Gilles Vassal has reported, 90% of the drugs successfully given to young people with cancer over the past 40 years have been used with different tumour types in adults. Ultimately, the legislation can only be made consistent and genuinely productive by basing the requirement to produce a Paediatric Investigation Plan on the biology that underlies adult cancers rather than simply the tumour type.
We acknowledge that some companies may conduct a PIP they are not required to and which may involve pursuing the mechanism of action. This may be the result of altruism or, more likely, because of the incentives the legislation offers. However, this is unlikely to generate research in anything more than a haphazard fashion. As parents, we expect industry to conduct paediatric research systematically and as a matter of course – our children deserve no less. This is why the Paediatric Regulation’s emphasis on requirements, which you yourself accept is what makes it different, is so important. The point is such obligations must be applied consistently and correspond with our current understanding of biological science.
It is of course heartening to read of the oncology PIPs currently proceeding, but, after ten years, these are still in relatively small numbers when one considers the scale of the problem to be overcome – 6,000 deaths of young people in Europe every year from cancer.
The urgency of the situation is distilled in the words of one parent:
‘It is inconceivable in this day and age that, globally, there is no drug that can cure my daughter’
This is the view of the nearly 1500 people who have signed our petition and of the many prominent professionals and associations (SIOPE included) that have come out in our support. If one reads the literature, there is a clear consensus in the professional community of the changes that are necessary to put the regulation on track and of the urgency of doing so. As members of the CDDF ITCC ENCCA SIOPE Paediatric Platform concluded at our conference this time last year: Waiting is not an option.
We look forward to a productive engagement with ENVI in the New Year. In the meantime, may we wish you and your staff a Happy Christmas.
on behalf of Unite2Cure