The biggest project on severe asthma to date
About 300 million people worldwide suffer from asthma, with 250 000 annual deaths attributed to the disease and it is estimated that the number of people with asthma will grow by more than 100 million by 2025. Despite these statistics, not many new drugs have been developed to treat this disease since the invention of corticosteroids in mid 1940s. That’s partly because corticosteroids work well for 92-97% of asthma patients and there was no strong commercial incentive to look for new drugs. However, 3-8% of patients—those with severe asthma—do not respond to corticosteroids or other existing treatments. What’s more, those patients require frequent hospital admissions and account for half of all the asthma healthcare costs.
The U-BIOPRED project was the biggest and most complex research project undertaken to understand severe asthma to date. It aimed to speed up the development of better treatments for patients with severe asthma by understanding the disease in more depth. More specifically, its main goal was to identify different subtypes or ‘handprints’ of severe asthma by adding complex biological markers to clinical characteristics, so that new treatments can better target the disease in different patients.
Groundbreaking discovery of asthma subtypes
This was done in several stages: first the researchers recruited 1 025 patients with severe asthma – both adults and children. Secondly, researchers took blood, airway, breath and urine samples of those patients and analysed tens of thousands of proteins and molecules looking for common patterns. They wanted to know if patients could be divided into subtypes based on a combination of those biomolecules as well as a number of other clinical indicators.
Analysing all this information in 1 025 patients and looking for patterns was no small feat but thanks to bioinformatics specialists in the project, it was a success. By the end of the project, the analysis revealed that there are four to five subtypes of severe asthma among adult patients (depending on the clinical and biological markers used), a discovery which is already paving the way for the development of more effective treatments. Initial results also show that there might be several, slightly different subtypes of asthma in children, but that analysis is still on-going.
Unprecedented cooperation and other achievements
In addition to discovering a number of subtypes of severe asthma in adult patients, the project recorded a number of other achievements, including:
- Reaching a consensus between industry and the academic partners on what constitutes severe asthma and how it differs from ‘difficult’ asthma. The consensus was published and is being taken up by others, such as the International Primary Care Respiratory Group. It will be updated in the near future to include final project results.
- Building a registry with data from 1 025 patients belonging to eight different groups (so-called ‘cohorts’), some of which have never been studied before. For example, the project included four different groups of children, from preschool wheezers to asthmatic school-age children. This is significant because no study has ever studied children of various ages in combination with adults before – until now they were considered young adults. The registry will be an asset in future research.
- Establishing exemplary cooperation between all project partners, including 12 pharmaceutical companies, academia and patient groups. According to project participants, the results achieved in this project could not have been achieved by one company or academic institution alone. It was a truly collaborative effort.
- Building a biobank with more than 50 000 severe asthma patient samples (e.g. blood, sputum, lung tissue, urine), available for future research.
- Creating a certified rhinovirus challenge model which can mimic asthma attacks or exacerbations. Exacerbations are a key unresolved problem in severe asthma and it is difficult to recruit patients when they suffer from them. Therefore this virus could be an important asset in future research.
- Nourishing exemplary patient involvement. Patients played a big role in the project, including participation in the scientific and the ethics boards. They helped in many aspects of the project, including fine-tuning research protocols and providing encouragement during difficult times. A handbook on how to successfully ensure patient participation in research was also produced.
- Producing almost 70 scientific papers which are now in various stages of preparation.
The data from U-BIOPRED to benefit companies, patients and academia
The knowledge and data from U-BIOPRED is already being used extensively by the pharmaceutical companies to address a number of key bottlenecks in drug discovery which will bring immense benefits to patients:
- Identifying and validating drug targets. As U-BIOPRED has mapped the biological processes of severe asthma in patients, companies now have a clearer view on which biological processes should be targeted with future drugs.
- Decisions on which drugs to invest in. Thanks to the U-BIOPRED data, companies can now predict whether some of the drugs which they have in the pipeline will be effective for severe asthma patients.
- Getting the right drugs to the right patients. There are already some new drugs for asthma and severe asthma which work in some patients and not in others. By using the handprints as part of clinical trials, companies and caretakers can now start predicting whether or not a certain drug will be effective in individual patients. In the long run, this will be very beneficial for patients because they won’t be unnecessarily treated by drugs which don’t work for their asthma subtype.
The project will also benefit the academic community as the knowledge, networks and experience gained will inform many future studies and collaborations.
What happens next?
Even though the official funding for the project ended, the analysis and validation of the data will continue through on-going contributions from various consortium members and other organisations such as the European Respiratory Society. In the long-term, the researchers will try to answer some of the following questions:
- How well do different subtypes of asthma identified in this project persist over time?
- Do individual patients move between different subtypes of severe asthma?
- Are the same subtypes of severe asthma present in other populations?
- What are the similarities and discrepancies of handprints between severe asthma and the chronic obstructive pulmonary disease?
Some of these research questions might be addressed in future H2020-funded studies and IMI projects.