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'Without IMI this would have never happened' – an interview with U-BIOPRED’s Peter Sterk

11/08/2016

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Peter Sterk 

IMI: After seven years, the U-BIOPRED project ended, and it has generated a lot of valuable results. As the scientific coordinator of the project, which three accomplishments are you most proud of?

Peter Sterk: To start with, we launched a new concept of how we look at disease. As opposed to the traditional medical diagnosis of severe asthma, we started from scratch and looked at abnormalities in individual patients, i.e. trying to capture the abnormalities which are causing the disease in a particular patient. We did that by measuring not only things that doctors are regularly looking at—such as the symptoms and the lung function—but we also looked at tens of thousands of molecules and proteins in the blood and the airways, even in urine and the breath. This allowed us to have a much better window into individual patients and it taught us that there are more types of severe asthma than just the severe asthma as such.  Without knowing that, we would never really be able to help patients with severe asthma—so that is one thing we’re really proud of.

Secondly, we can be proud that we had not only professionals in the project right from the start—doctors and scientists from the academia and industry—but also patients. This taught us to better focus our research questions and to really critically look at our methods. For example, can we really ask patients to come so many times to do this or that test? Having patients on board also really encouraged us and inspired us to push on in difficult times. The patients were really important.

Thirdly, everybody is talking about big data at the moment. But who is doing it? Well, we did it, we are doing it. We’re doing it by really bringing concrete ways of analysing all those molecules and all those clinical abnormalities in individual patients. When we started the project nobody knew how to do this with statistics and mathematical solutions. During the course of our project, experts in our consortium really solved the main challenges of how to combine all this big data and shape them into concrete answers. It was not easy but it has been done. U-BIOPRED was one of the first—perhaps even the first—to do that.

IMI: The discovery of different subtypes or handprints of severe asthma is really groundbreaking. Could you explain a bit more about how this knowledge is already being used by the drug companies?

Peter Sterk: Drug companies are trying to discover and develop new medicines for patients with severe asthma because these patients do not respond to regular treatment. For example, there are new opportunities for interventions into the biological processes in the lungs, but which one to choose? There are two ways in which U-BIOPRED is already contributing. Firstly, because we have mapped the biological processes of severe asthma patients, companies now have a more clear view on which biological processes should be targeted with drugs and which not. Secondly, companies already have some very interesting drugs which block molecular pathways of cells in the body and lungs. Now they can more easily answer the question: could those be of interest for severe asthma patients? They can look at those pathways and the drugs that are available and predict whether some of these drugs will be effective for severe asthma patients. So, yes, drug companies are already using U-BIOPRED data to look at their existing drugs and make decisions on which ones to invest in.

Finally, there are already some new drugs for asthma and severe asthma and they work in some patients and not in others, and the companies don’t know why. That’s why they are now using the U-BIOPRED handprints at the beginning of clinical studies. First, patients’ asthma handprints are being determined, then patients are being treated and at the end the respondents to treatment and the non-respondents to treatment are being compared to their handprint at the beginning of the study. Can we predict efficacy of the drug based on the patients’ handprints? This is the most interesting part of using the U-BIOPRED data.

IMI: Could you say how long it could be before patients start seeing improvements in their treatments as a result of this project?

Peter Sterk: When it comes to improving the selection of the existing drugs or the new drugs that are already reaching patients, we could already see results within the next two years or so. There will be a huge benefit for patients because they will not be treated unnecessarily with drugs that don’t work for their subtype of asthma. For new drugs which will be developed based on the subtypes of asthma, it will certainly take longer to see the benefits.

IMI: In addition to adult patients, this project looked at severe asthma subtypes in children. Nobody has ever studied children’s asthma of various ages in combination with adults before. Could you tell us a bit more about that?

Peter Sterk: Indeed, children were considered small adults until now, which is not the case. Diseases, including airways diseases like asthma, are really not identical in kids compared to adults. Disease is developing; it’s evolving, changing with age. That’s why in U-BIOPRED we also included the preschool wheezers: children that have a severe wheeze at 3-4 years of age and some of them become asthmatics later on and some don’t. We would like to understand the abnormalities of those children who are becoming asthmatics later on: are those the same as the abnormalities of asthmatic school children, and are those similar to others? We wanted to have the full spectrum. We don’t know the definitive answers yet but I would say that the biological fingerprints and handprints in children are at least partially different than in adults and that will require specific interventions in kids as opposed to just using the drugs that have been developed for adults. This could really have big implications for the future. The development of specific treatments for children could take some time, but—yes—another thing to be proud of is that we have children on board.

IMI: How many asthma subtypes did you discover in adults and how many in children?

Peter Sterk: We discovered 4-5 subtypes of adult severe asthma, depending on the clinical and biological used. For children we still don’t have definitive answers. For adults, we were positively encouraged by the results—the fact that it is not 20 subtypes or just 2. Having 5 or 6 subtypes is manageable in terms of medical stratification.

IMI: How did the collaborative nature of IMI’s public private partnerships contribute to the project? Could the same results have been achieved without IMI?

Peter Sterk: Without IMI this would have never happened because it is one thing to get the academic centres around the table—we know each other even though we are competitors. But sitting together with companies is another thing. Academics are sometimes working with companies one-on-one, but 12 companies sitting together around the table with academics—that has never been done in this field, ever! It has built a lot of confidence and trust among the scientists in the academia and companies but also at higher layers in the companies—we know now that it is possible to collaborate in a pre-competitive way. Trying to understand asthma in terms of biological mechanisms benefits all the companies and they cannot do it on their own. They can only do it collaboratively, together with the academics, and after that they can develop their own drugs and start competing again. The uniqueness of this project was the collaboration of all those companies and academics around the table. There were never problems with companies not being open to each other, keeping data for themselves or academics not sharing.

The involvement of patients was also very important; we asked them to participate in a way that has never been done before. We could have done it even better from the start but luckily patients increased their level of involvement during the project themselves. We asked them to contribute at the beginning on a fairy small scale but because of their commitment to working with us, they increased their level of involvement. They were in the ethics board and in the safety monitoring board, they had a patient input platform and they were in all our work packages. And I would have loved to have them in the managing board but that would have had to have been decided at the beginning. The cooperation was very fruitful. There is no way of getting a good project anymore without the patients—if you do research with scientists, doctors and patients on-board it is so much better, there is no question about it.

IMI: Apart from being transformative in terms of results, you mentioned that the project has been transformative for the people in the project as well. How has it been transformative for you personally?

Peter Sterk: This project transformed my thinking about the concept of biologically sub-typing patients.  It also transformed my collaboration with international colleagues. Yes, we know our colleagues and we sometimes do things together but this project was based on a very intensive collaboration with colleagues in various European countries. It changed my way of working with the industry, with patients, and in fact changed my career at my university. Being involved in U-BIOPRED gave me a wealth of information, enthusiasm and modesty in terms of collaboration. It was a backbone of all my research during the last 8 years or so and all my other projects were somehow connected to this big project. If I hadn’t had the opportunity to work in U-BIOPRED I would have been a different scientist and a different player in the field – that is absolutely certain.

IMI: What is the most rewarding aspect of this project for you personally?

Peter Sterk: The most rewarding thing is that we now have scientific data showing the subtypes of severe asthma that are being recognised and appreciated by all the partners in the project: the patients, the scientists from EFPIA and the academia. We all recognise that we discovered subtypes of asthma that were not known before. The rewarding thing is that this was a collective/collaborative effort—we did this together. Yes, at the end of the road, our statisticians identified the subtypes after all the collection of the data, but they know that they wouldn’t have been able to do it without the clinicians nor without the patients. It was a truly collective thing and that’s the most rewarding element. Also, there is not a handful of people who are running away with the results—it is all of us.

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