Let’s Do #More4KidsCancer – Support Our Campaign by 15 Dec 2016

Between now and Thursday 15th December 2016, support our online campaign Let’s Do #More4KidsCancer to act in favour of children and young adults with cancer.

more4kidscancerSIOPE, CRUK and Unite2Cure are calling for EU institutions and civil society to speed up the development of safe and effective anticancer therapies for children and adolescents, as the European Parliament is voting on a Resolution about the EU Paediatric (Medicines) Regulation.

In Europe, less than 1 in 10 children with a terminal cancer have access to potentially life-saving innovative medicines. Ten years after its approval, the EU Regulation did foster progress in paediatric drug development but remained insufficient for paediatric oncology. Too few drugs targeting childhood cancers are currently under development, despite cancer remaining the first cause of children’s death by disease in Europe.

Support our cause by clicking here: it takes 5 seconds to join our campaign and it is very easy to do.

For our campaign, we are using the “Thunderclap” tool: it allows people to pledge a Tweet/Facebook message with our important message, and unleash them all at the same time on 15th December, thereby “flooding” the web. Think of it as a “Twitter flash mob”.

If you are active on social media, we would like to ask you to add your support via Twitter or Facebook, by using #More4KidsCancer, or even posting something gold/a golden ribbon to show that you understand the fundamental importance to increase cure and quality of treatment for children with cancer.

With your contribution, our voice will be stronger!

Thank you very much,

SIOPE, CR UK and Unite2Cure

It’s about acceleration

Professor Pam Kearns talks frankly about clinical trials and children’s cancer.


If you search on Facebook, you can find a picture of Pam Kearns with ‘the girl whose life she helped save.’ In the photograph, doctor and patient share a relaxed smile and an obvious affinity. Pam was Paige’s clinician after the 11 year-old fell ill with Wilm’s Tumour, a rare form of kidney cancer. However, the role she plays in helping children like Paige is not just that of providing treatment. She is Director of Cancer Research UK’s Clinical Trials Unit and a leading figure in the search for new ways to combat paediatric illnesses like Wilm’s.

Paige’s story is a heartening one but if you go to hear Pam speak, she will show you another side of the picture, flashing up on a Powerpoint slide the words of different child’s father:

‘It is inconceivable in this day and age that, globally, there is no drug that can cure my daughter’


Any child diagnosed with cancer faces an uncertain future and to find out more about why this is so and what can be done about it, I went to visit Pam at the Clinical Trials Unit in Birmingham on a sweltering morning this June.

Pam and I have known each other for 5 years through involvement in various projects to do with childhood cancer, but I had never visited her on her ‘home turf’ and I was curious to know how the ‘nerve centre’ of childhood cancer research in Britain operates.

She welcomed me into a surprisingly modest office she shares with a sleek, carbon-frame Cannondale, the bike she uses for a 20 mile daily commute and the sportive challenge she promises she will get round to soon.

I start at the beginning and ask her what exactly the Clinical Trials Unit does.

‘Lots of people don’t know what a Trials Unit is and that includes many clinicians. There are about 30 Trials Units within universities in the UK, of which about a dozen or so are dedicated to cancer and 8 are core-funded by Cancer Research UK.

‘The aim of a Trials Unit is to be the place where an investigator comes with an idea about improving treatment, whether it’s giving radiotherapy in a different way, introducing a new drug, a new type of surgery, any clinical idea that changes the patient pathway. We work with them to see if it’s a viable idea and if it is, we help design the trial, collect the data – everything from concept to completion; the only thing we don’t do is recruit the patients.’

Who pays the piper?

I ask her who funds the research.

‘By far, the majority of paediatric cancer trials are charity funded. Cancer Research UK (CRUK) is our biggest funder; they fund the core team (at the Clinical Trials Unit) and if a trial is good enough, they’ll fund the trial too. We sometimes manage to get into collaborative partnerships with the pharmaceutical industry where they will give us a grant and a drug to support the trial.’

She gives the example of a major investigation into leukaemia.


Figure 1: 2008 Spend on Children’s Cancers (NCRI 2014)


‘ If you look at the AML trial which we’ve just launched, that has a lot of questions about how to use standard chemotherapy, but it’s also got a drug called mylotarg, which industry are still trying to get a licence for. The majority of the funding is from CRUK but there’s also a large grant from Pfizer – plus the drug. So that’s a true partnership, where you’ve got charitable funding delivering the academic questions plus Pharma contributing to answers we are interested in – important to patients, to families, but because they are also interesting to Pharma, they are investing money in it.’

She goes on to explain, though, that ‘we don’t necessarily need the industry’s involvement if, for example, we’re asking questions that are about generic drugs.’

When she refers to generic drugs, she means ones that are already commercially available. She explains that in past decades, many of the advances in children’s cancers were made by simply repurposing generic drugs originally licensed for use with adults. Even in the present day, a lot of research simply involves revisiting generics already well-established with children, refining their doses and tweaking their combinations. This process, however, she argues, has run its course.

Big Pharma and Small Biotechs

‘We’ve hit a plateau of improvement in many diseases,’ she explains. ‘To make the step changes we need in the future, I don’t think we are going to achieve that by just using generic drugs. We need new approaches, new drugs with different mechanisms of action that we can add to our armoury. That’s when we need the industry to give us access to their new drugs and innovations.’

The revolution in genetic science in recent years has stimulated a new wave of commercial drug development. These are the so-called novel agents that target illness at a molecular level and which hold great potential for shifting children’s cancers off the ‘plateau.’

Going ‘off-label’

A drug is usually licensed to treat a specific type of disease or cancer. If doctors feel that a particular drug may help a patient with a condition not included in the drug license they can prescribe that drug for the patient. But the doctor has to take full responsibility for the outcome. This is called ‘off label prescribing’. Many clinical trials for cancer use medicines ‘off label’ in this way. The trials want to find out whether drugs licensed for a particular type of cancer could help to treat other types of cancer.
Read more at http://www.cancerresearchuk.org/about-cancer/cancers-in-general/cancer-questions/how-are-drugs-licensed-in-the-uk#XADUiGrOvPXKyVEt.99

The problem is that the pharmaceutical industry is adult-orientated. Its focus is on the blockbuster markets created by the common cancers that afflict older people, rather than on the messy patchwork of rare conditions that are children’s cancers. Pam’s concern is with the delays involved in waiting for new agents to be commercially developed for adults before we investigate their potential in children.

‘If there was a generic drug, a drug that had come off its licence now,’ she explains, ‘ and that was being used for adult cancer and we wanted to use it in children because we had scientific evidence that it could make a difference, we could go ahead and do that. 

‘But what we’re saying is, “Look, drug companies with your massive pipelines of new drugs, you’re developing targeted drugs that would be useful to children now not when that drug has been developed for adult illnesses.”

‘It’s about acceleration. We could wait until X or whatever targeted drug has been licensed for adults and then repurpose it for children and just carry on the way we have before. But we’re delaying access to children by sometimes 30 years. So the whole purpose of this is getting into the drugs pipeline really early, before the drugs are on licence in adults and let’s see if they’re interesting in children.’

I ask her why we are so dependent on the private sector.  Could not research centres in universities or hospitals simply develop the drugs themselves? The answer, of course, is about money.

‘It costs a huge amount of money and there’s high attrition rate [ in drug development] and academic departments would struggle to do that. I’m not saying they don’t exist. There are drug discovery units, for example at the Royal Marsden’s Institute for Cancer Research but they can’t turn on the high throughput screening in the way industry does. If an academic department developed a drug, there is no reason why we would not work with them, but at some point they will hand on the further clinical development to a small biotech and if it’s good, it will be bought up by Pharma. It’s the money that’s required to develop the drug.’

She gives an example from Birmingham.

‘My colleague, Frank Mussai, he’s doing some really interesting work looking at a particular pathway relevant to childhood cancers, and he’s found a biotech company based in Asia who produce the drug that targets this pathway. They’re not rich and they haven’t got the expertise to do the clinical trials, so they’ve been giving him small amounts of money to do his lab research. They’ve been giving him access to the drug to develop the laboratory research. Today we have finalised a grant application to the charity sector to do a trial in paediatric cancers .

‘Now if that drug were ever to become a blockbuster, then we would get some of that investment back so that we could develop the next set drugs. But that would be a rare event.’

From Brussels to Birmingham

The conversation inevitably shifts to the measure the European Union introduced to stimulate commercial interest in children’s drug development, the Paediatric Medicines Regulation. Both Pam and I are involved in campaigning to reform the Regulation and are aware of its disappointing record to date. However, she emphasises that it has had an effect.

‘I can remember the days, ‘she says, ‘of going to big cancer conferences and talking to a Pharma company at a stand about drug that was relevant to my research and they were really interested in talking to me as a medic until I said I was a paediatrician and they were like, “How quickly can I get this woman away from me?”

‘And that attitude has changed and it’s changed because of the Paediatric Regulation. There is a benefit; it might not have translated into new drugs for children but a positive attitude change has happened. ‘

I ask her about a similar campaign she was involved with, around another piece of Brussels legislation, the Clinical Trials Regulation.

‘It feels like it was a huge chunk of my life,’ she sighs. ‘But it was only two years’ serious campaigning  ’

The important point, though, was that the campaign was broadly successful and layers of unnecessary bureaucracy that hold trials back are scheduled to be peeled away.

What did you learn, I ask her, from the experience of that campaign?

‘That you had to work with the European Parliament and the relevant rapporteur,’ she says. ‘But rather late in the game we realised if you don’t have the European Council on board, the changes you want could be voted out. I think we were quite late in engaging with the member states. For the UK, we were in a better position because the MHRA (Medicines & Healthcare Products Regulatory Agency) were taking the role  on behalf of the Health Minister and they were sympathetic to the changes we wanted, so we were pushing at an open door. But that wasn’t the case across Europe. We met with health attaches from one of the member states and they were still concerned with clinical research in children being unethical. So they were miles away from where we wanted them to be and they were the people sitting around the table at the vote.

‘This is what we need to remember with the Paediatric Medicines Regulation. We know the arguments inside out but when you sit down with someone for the first time, they’ve only got this vague idea what you’re talking about so getting that sound bite, that message across is really important.

That’s what I learnt.’

Ethics and Equipoise

I pick up on the worries about the ethics of involving children in research   and ask her to explain about randomised trials.

Phase 1, 2 and 3 – What’s the difference?

Clinical trials are often divided into three stages or phases. Earlier phase 1 trials focus on how much of the drug it is safe to give and whether it actually shrinks the cancer. If a phase 1 is successful, the therapy will be tested more extensively in phase 2 and 3 trials. A new treatment usually needs to go through phase 3 before it is accepted as standard.

Phase 2 and 3 trials are often randomised. This means that people taking part in the trials are divided into different groups at random, with each group being given a different treatment or arm. Trials that compare three or more treatments are called multi-arm trials.

Read more at http://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/what-clinical-trials-are/randomised-trials#LYP4pAsEKZRIDbcs.99

 ‘When you are doing a randomised trial, there should be no prior knowledge or belief that one arm is better than another. This is what we call equipoise. As a clinician, when I sit down with a family and I ask a child to participate, I can explain the background to both the arms but I should be able to say, hand on heart, I don’t know which one is better. If I did know, it would be unethical to ask someone to take part. ‘

She refers to the major randomised trial into Ewing’s Sarcoma, the illness my own daughter had.

‘It is like Euro Ewing’s 2012. Do you want to participate in a comparison of the known gold standard in Europe against the known gold standard in America? We cannot differentiate between the two and now we are asking the question which is more effective and which has fewer side effects.

‘Equipoise is about randomised trials. However, there is no equipoise at phase 1.

‘In a phase 1 trial, the ethical question is that you are asking a parent for their son or daughter to participate in a trial that may not have benefit for their child.

‘Now you can  ask an adult to take part in a phase 1 and it’s that adult’s informed decision on the basis of altruism and, undoubtedly, a little bit of hope that they’re going to get the “miracle response.”

‘The Declaration of Helsinki states, however, that you cannot do clinical research in children when there is not at least the potential for benefit, which means you cannot do the type of  ‘first in man’ studies you can in adults, starting from very low doses. There needs to be evidence from laboratory research or clinical trials in adults that suggests the treatment could have a benefit at the doses given to a child.

Talking to families

I ask her how she puts the option of a phase 1 trial to parents and child.

‘If I can give this in very personal terms , when I sit down with a family to talk about a phase 1 study, particularly a family I have never met before, the first thing I do is establish their understanding of where a child is in (I hate the expression ) the “cancer journey.”

‘So do they understand their child has no curative option? And that it’s effectively palliative at that stage? Because, without that understanding, the rest of the discussion about the phase I trial is almost dishonest. The eligibility criteria for most phase 1 studies is that there is no known better curative option. I then explain to them the background to the trial but I also say what the other options are and those might be purely supportive.

‘It might involve  using a drug like etoposide. We don’t have a lot of published data to prove this  has benefit but substantial clinical experience tells us that it has some success in holding back the progression of disease in some children.

‘I’ll explain where the trial is in terms of the drugs development, what the implications are of being in that particular trial. Does that mean more time in hospital, more blood tests, more investigations, backwards and forwards from half way across the country to visit me?

‘I outline all that.

‘I strongly dissuade families from going, “Where do sign?” ‘I always say, “Go away and think about it, talk about it.” And I talk to the child about it, depending on their age.

‘Morally, ethically and within the Declaration of Helsinki, you never ask a child to participate in a trial where there is no evidence of benefit. But the chance of the benefit has to be understood to be quite small and then it comes down to the motivation of the family and the child and whether they want, at least, to try something.

‘Now my experience is that each family is different. You get some families that respond saying, “I don’t really want to have anything more to do with hospitals – that means we can have some life together for a while.” They’ll do that. They won’t participate in phase 1 clinical trials – and that’s fine.

‘Then you get the different kind of family that says, “Whatever there is. They want to know if a phase 1 trial fails, what’s the one after that and what’s the one after that. They want to keep going. They want to be involved in something that brings their child to the hospital and might have the potential for a miraculous benefit.

‘There’s another kind of family. Often it’s done with the involvement of the child in the decision making; for example, slightly older children. They really know there isn’t much chance of benefit but they feel they want to be doing something, even if it is for someone else. That’s extraordinary, in my mind, but parents have said to me that at least we tried to do something even if that something is for somebody else.

‘I am forever in awe of all three sets of families. None of them is making a right or wrong decision. My job as a medic is to listen and answer questions and hope they go away feeling they have made the right decision for them and their child.

 ‘It’s a hard area and that’s why it shouldn’t be done in every centre in the country. It must be done by people who have that experience of talking to families about these issues.

‘Most of our experience is in breaking bad news to parents, because the majority of children treated are very young. It is harder to gain the experience of breaking this type of bad news to  the age group of children who are just starting to be old enough to understand.

I remember doing it for the first time when I was a junior doctor and I can remember, to this day, this teenager whose disease had become incurable quizzing me really hard about what was going to happen and I wanted to run away from the question’

‘It would have been really easy to say, “It’ll be fine” and patronise this teenager. But I stuck in there and that is something we all need to do.

In passing, I mention the difficult exchanges we had with our consultant over the only trial my daughter was offered in the whole period of her relapse. I relate the mobile call just before Christmas in which we turned down a phase 1 study of aurora kinase, a drug I have heard nothing of since in relation to Ewing’s.

‘That’s because the clinical development was abandoned,’ says Pam, ‘because it didn’t work. They completed the study but it wasn’t effective in anybody.’

Compassionate Use

We talk about the children who are never offered the option of a trial – because the trials are full, because the children do not meet the eligibility criteria or, as is more often the case, because the trials are simply not running.

I ask her about compassionate use, which allows patients access to new medicines, even hough they are not enrolled on a trial.

‘Compassionate use exists in America. We’ve got it here too. It’s called “Named Patient Access.”

‘As an example, it is possible for a child with leukaemia to get access to inotuzamab, even though there’s no trial open for that drug at the moment. We could open the trial of this drug when we get through all the regulatory paperwork. Compassionate use of drugs cannot substitute for proper drug development because we’ll never know if we just use it compassionately whether the drug should be properly developed and marketed and available to everybody.

I push her on whether we can get more children off phase 1 and onto phase 2 studies, where the emphasis is less on the safety of the drug and more on its efficacy. She talks about a new trial.

‘That’s the aim of E-smart. It will have multi-arms and, as new drugs become available and they’ve got their safety data, we can slot them into the trial. When the child has that molecular pathway identified, it doesn’t matter whether it’s Rhabdomyosarcoma or Ewing’s, does it have the target for that drug, can they enter the trial? And we’ll just keep that trial open and growing as long as we can get access to the drugs and that’s the sort of trial we need more of.’

Reference: NCRI (2014) Funding of children’s cancer research. Accessed 19 June 2016 at: http://www.ncri.org.uk/wp-content/uploads/2014/02/2014-NCRI-childrens-cancer-research-analysis.pdf

Article written by Chris Copland, Unite2Cure

New drugs for childhood cancers: could biotechs end the drought?

An article in Cancerworld magazine by journalist Sophie Fessl, summarizes well the issues Unite2Cure is raising.


The chances of surviving a childhood cancer have changed very little over the past two decades. Sophie Fessl talked to parents, doctors, regulators and researchers about what has to be done to address this disastrous impasse. “It feels odd to say this, but Elliot is one of the lucky ones.” The comment comes from Nicole Scobie (photo, above, with Elliot), and refers to her son, who was only four years old when he was diagnosed with a stage IV Wilm’s tumour. His left kidney was engulfed by a huge cancerous mass and his lungs were full of metastases. The heart-stopping diagnosis was just the start of a rollercoaster of emotions, hospital stays and exhaustion. But this is a story with hope: Elliot responded well to chemotherapy. He went into remission after 10 months of treatment, and has remained so for the past four years.


“At least for his cancer, there is a treatment that works,” says Nicole. Not all the children she and her son befriended during their long stay at the Lausanne University Hospital’s children’s cancer ward can consider themselves as ‘lucky’. Elliot became close friends with Zoe, a little girl battling an aggressive neuroblastoma. But while Elliot’s prospects looked good, for Zoe, the odds were stacked against her. In the end, there was nothing her medical team could do: Zoe died in her mother’s arms aged four.

The difference between Elliot and Zoe? Elliot had a type of cancer that has been successfully treated for decades, being one of the first childhood cancers – alongside acute lymphoblastic leukaemia – to benefit from the chemotherapies pioneered by Sydney Farber back in the 1950s. His is part of the celebrated success story that saw cancer survival rates among children increase from 10% to 80% over 50 years.

Zoe, by contrast, had a type of childhood cancer that remains fatal in the majority of cases. Her story is shared by 6,000 children and young people under 24 who are still dying of cancer each year in Europe. For parents like Nicole Scobie, who’ve seen their child’s life in the balance, that is a heartbreaking statistic. But there’s a worse one – the mortality rate from childhood cancers has barely changed over the past 16 years.

Last year, Scobie was one of a large group of parents and advocacy organisations that got together to found Unite2Cure, an advocacy organisation that aims to kickstart progress again.

Read the full article online here or download in PDF format here

An Update from the Unite2Cure Team

Where do we go from here?

Here is an update on the state of play regarding the campaign on the Paediatric Medicines Regulation (PMR).


A Resolution to be put before the European Parliament has been drafted by members of the European Society for Paediatric Oncology, Unite2Cure and Cancer Research UK. The Resolution has now been been approved for debate in the Parliament and we expect this to take place in Strasbourg by the end of October. It is being sponsored by Francoise Grosstete of France and Elena Gentile of Italy. It will give a clear message to the Health Commissioner to act boldly in the forthcoming Review of the PMR.


Prior to this, there will be a special meeting of MEPs Against Cancer (MAC) Group in the European Parliament on 7 September, which will call for revision of the PMR. We hope to organise a ‘stunt’ (eg. a human ‘gold ribbon) to coincide with one of the above meetings.


Unite2Cure ‘ambassadors’ are working to lobby national politicians to exert influence on their representatives in the Europe, including members of the Council. In France, there was a lobby dinner for the Senate on 28 June. An extraordinary session on the PMR wiil be held at the European Council on13 September, arranged by French Health Minister. In the UK, a meeting is being sought with the Life Sciences Minister and appointments have already been made with the UK Research Attache and Health Attache. ‘Ambassadors’ are working in Germany and Italy on similar lines.


A public consultation on the PMR will be launched by the Commission in the autumn, in which we have been invited to participate.



What part can you play?



When we have a date for the debate to be held in the Parliament, we will be asking supporters to mobilise their networks in a letter writing campaign to MEPs.


If you want to get involved as am ‘ambassador’ in your country, contact unite2cure@gmail.com


A Note on BREXIT


The ‘leave’ vote in the recent referendum in the UK is a matter of great concern for those who wish to see collaboration on cancer research in Europe and to use its democratic institutions to this end. However, article 50 has not been invoked and even if Britain does begin withdrawal from the European Union, this process is likely to take many years. Given the level of uncertainty, British MEP, Glenis Wilmott, is allowing French and Italian representatives take the lead, though she is still fully engaged in the process.


Unite2Cure is, therefore, continuing with ‘business as usual’ and is optimistic of the results we can achieve through 2016 and 2017. We have everything to play for. The continued collaboration of supporters within the EU and beyond will be greatly appreciated.




A Response from the Commissioner to the Golden Letters

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 .

This very productive meeting was also the opportunity to give the Commissioner 200 golden letters from parents and organizations across Europe: together we are stronger!
Yesterday, we received the following letter by post, in reply from the Commissioner.

Unite2Cure Meets with the EU Health Commissioner

UNITE2CURE at the European Commission to meet with Health Commisioner Vytenis Andriukaitis: Changes are needed to  the Pediatric Medecine Regulation

Patricia Blanc, Chris Copland, 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 .
This very productive meeting was also the opportunity to give the Commissioner 200 golden letters from parents and organizations across Europe: together we are stronger!
We also had a working session on the PMR and next steps with the other participants of the delegation:
Pr Gilles Vassal and Pr Pamela Kearns, Olga  Kozhaeva from SIOPE, Catherine Guignard from CRUK , MEP Glenis Willmott, and her parliamentary assistant Emily Hunter and Remy Petitot parliamentary assistant of MEP Françoise Grossetête.
More information to follow.


Unite2Cure at the Childhood Cancer International European Conference


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: unite2cure@gmail.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 unite2cure@gmail.com





Time for Change

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

Making better use of known drugs in treating children with cancer

Given the mountain we still have to climb when it comes to treating childhood cancers, it seems wise to explore all possible paths to new treatments.

Drug development is notoriously risky and expensive. This creates a formidable barrier to the introduction of new medicines for children with cancer as the pharmaceutical industry prefers to invest in the development of drugs for the much larger adult cancer population, which holds the potential to repay for the heavy investment and risk. With very few exceptions, specific drugs for children with cancers are not developed and the only hope for sick children is that at some point some of these “adult” drugs will be tested and eventually used in children.

This is far from ideal as children and adolescents with cancer do not have the time to wait. New treatment options that are more effective and safer are urgently needed. While we at U2C are busy working on introducing more effective incentives for companies to develop new medicines for childhood cancer, there are some possible approaches that may bypass the above mentioned hurdle and may be championed by parents’ organisations.

These approaches include drug repurposing and metronomics.

Drug Repurposing, sometimes also called drug repositioning, is the re-use of an existing drug for a new disease. Very often a drug is developed to treat one illness and it is later discovered that it can treat another as well. In the case of cancer, there is evidence that a range of non-cancer drugs may also have anti-cancer effects which may be clinically useful. These drugs, many of them commonly available as generics, are cheap and have low toxicity as well as decades of clinical use for their original uses. While there is a range of evidence to support the anticancer effects of these non-cancer drugs, including some antibiotics and antifungals, there is a need to develop and run clinical trials to put the anticancer effects to the test in the same way as we do with other potential cancer drugs. However, because these drugs are generic there are no commercial incentives to run expensive clinical trials or to license the drugs for new uses if the trials succeed. Therefore, in addition to medical innovation there is also a need for financial innovation to overcome the regulatory barriers to change. Another potential advantage of this approach is that very often these repurposed drugs have been used already in children and adolescent for the treatment of other disease, therefore we would have confidence on the safety of these “old’ drugs in the treatment of children with cancer. This is not a trivial benefit in view of the well-established toxicity of currently used cytotoxic agents.

There are many examples of successful repurposing already. Methotrexate, one of the first drugs developed to treat childhood cancer, is now being used to treat arthritis. Propranolol, used to treat high blood pressure in adults, is now used to treat infantile hemangioma, a disfiguring and sometimes dangerous benign tumour in babies and toddlers. Thalidomide, a drug notorious for causing birth defects when used to treat morning sickness is now being used to treat leprosy and multiple myeloma. This is the only successful example of repurposing a non-cancer drug in oncology, but there is evidence that many more drugs have the potential to do the same.

Metronomics is another approach to drug development that has the potential to impact childhood cancers. Conventional chemotherapy remains the mainstay of treatment in both adult and childhood cancers. It is normally delivered at high doses and is associated with a range of side effects including hair loss, nausea and vomiting and neutropenia (increasing the risk of infection). However, many of these very toxic drugs also show signs of anticancer activity when used at very low doses. Using the drugs at these low doses means that the side effects are minimal and that there is no need for treatment breaks for the body to recover – mostly the drugs are given orally and every day (hence the term metronomic chemotherapy).

In contrast to high dose chemotherapy, metronomic chemotherapy does not cause neutropenia and in fact the evidence suggests that it can boost the anticancer activity of the immune system. The other main action of metronomic chemotherapy is to control the blood supply to the tumour, cutting off the nutrients and oxygen that tumours need to survive. While there have been many clinical trials of metronomic chemotherapy in a wide range of cancers, including some very hard to treat cancers, there is a need for large definitive trials in pediatric cancers. As with drug repurposing the challenges are not just medical but also financial as many of the drugs suitable for metronomics are old generic chemotherapy agents such as cyclophosphamide and methotrexate.

Drug re-purposing and metronomics are just two example of innovative approaches for the development of new treatments for children with cancer that hold the potential to deliver quicker benefit to patients. If you want to know more and hear about some examples of ongoing projects in the childhood cancer area please do not hesitate to contact us.

Cesare Spadoni
Pan Pantziarka




Ashburn TT., Thor KB. 2004. Drug repositioning: identifying and developing new uses for existing drugs. Nature reviews. Drug discovery 3:673–683.

A letter to the Commissioner

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[1]. 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[2]. 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[3]. 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[4] 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[6]. 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[7].  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[8]. 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[9]. This is opinion of countless patients/parents’ organisations united under the Unite2Cure umbrella[10]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.

Kind regards,
The Unite2Cure Team


Founding Members

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)

[1] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4204542/

[2] http://www.fda.gov/; https://www.centerwatch.com/drug-information/fda-approved-drugs/therapeutic-area/12/oncology

[3] http://www.nature.com/nbt/journal/v32/n1/full/nbt.2786.html

[4] http://ec.europa.eu/health/human-use/paediatric-medicines/developments/2013_paediatric_pc_en.htm

[5] http://www.ema.europa.eu/ema/index.jsp?curl=pages%2Fmedicines%2Flanding%2Fpip_search.jsp&mid=WC0b01ac058001d129&searchkwByEnter=false&alreadyLoaded=true&isNewQuery=true&keyword=Enter+keywords&searchType=Invented+name&taxonomyPath=&treeNumber=&currentCategory=Oncology

[6] EMA Officer – Personal Communication

[7] On-Kos Consulting – Personal Communication http://www.on-kos.it/

[8] http://jco.ascopubs.org/content/27/31/5175.full

[9] http://ec.europa.eu/health/files/paediatrics/2013_pc_paediatrics/37-siop.pdf

[10] https://unite2cure.org/