IMI Programme Office: Why was a project like Pharma-Cog needed in the first place?
Régis Bordet: We have a problem with the development of drugs in Alzheimer’s disease (AD), because many potential molecules and mechanisms are out there, but many of these drugs fail in terms of efficacy and safety before they reach the market. With Pharma-Cog we wanted to increase the success rate of new drugs in development. We focused on the early phases of development between the last experiments in animals, studies in healthy volunteers, and the first phase which involves patients.
IMI Programme Office: Régis, as the scientific coordinator of the project, which achievements are you most proud of?
Régis Bordet: Firstly, there are two approaches to Alzheimer’s disease treatment – the first one is trying to improve symptoms – the symptomatic approach – and the second one is attempting to slow down the evolution of the disease – the disease modifying approach. Sometimes in the medicine field, there is some opposition between those two approaches. In Pharma-Cog, we demonstrated that both approaches are necessary for patients. Since we had one team working on the symptomatic approach and another team working on the disease modifying approach, we were able to put them under the same umbrella and show that the two can work together.
We have also improved the translation between animal and human studies, and we have identified biomarkers, such as EEG recording of brain activity and MRI scans, which could help predict the effect of drugs more accurately. For example, we have demonstrated that some changes in the rhythm of brain activity observed via EEG are a good marker to detect the effect of a new drug and to compare the size of that effect with an already existing drug. If the size of the effect is not so big, that means that it is not interesting to continue the development of this drug. This could make drug development faster, cheaper and more efficient.
Last but not least, we have built a huge database which contains all the results generated in Pharma-Cog. Since some of the clinical trials are still ongoing and we have not analysed all the data yet, the database is still not public, but we will make it public in the future.
IMI Programme Office: One of the project achievements was also patient stratification which could lead to more efficient clinical trials in the future… Could you explain what that means?
Régis Bordet: One of the limitations of clinical trials is variability between patients. For example, in patients with mild cognitive impairment (MCI), there are patients who will go on to develop AD and those who will not. If we test a disease-modifying drug in a group containing both types of patients, the potential effect of a drug could get masked by the variability in the group. In our project, we found biomarkers that predispose people with MCI to develop AD. Thanks to those biomarkers we can now identify patients who are prone to develop AD and focus on those patients when testing disease modifying therapies.
IMI Programme Office: Jill, you joined the project a bit later on, as the EFPIA project coordinator. Which achievement are you most proud of?
Jill Richardson: One of the major project deliverables was the AD patient study, measuring the changes in the matrix of biomarkers in MCI patients. When I joined the project, only 11 patients had been recruited into this study and we had to make some tough budgetary decisions to enable another five clinical centres to join the project and ensure that our recruitment goal was met. It is quite challenging to recruit patients for an investigational study in which no drugs are involved. But we did it, and recruited nearly 150 patients, which ensured the study was sufficiently powered.
As part of this study, we were characterising MCI and taking measurements of many different parameters at baseline and over different time periods. At the end of the study, we mapped the course of the disease through these different parameters.
I can’t think of many studies that measure biochemical and functional biomarkers, all harmonised across different clinical centres. Beyond the data, which is pretty impressive, there are now centres around Europe working together using harmonised technologies and methodologies, which should simplify recruitment for future AD clinical trials. That’s definitely one of the main project achievements and also being able to do more sensitive clinical trials in the future as a result of this patient stratification.
IMI Programme Office: Régis, would you say that Pharma-Cog made a significant contribution to the Alzheimer’s disease field?
Régis Bordet: Yes, it has. We are convinced that Pharma-cog contributed to improving the way we develop drugs in the field of AD. I can give three concrete examples of our contribution. Firstly, we made a contribution to improving the translational exploration of new drugs by using new common experimental paradigms in both animals and healthy volunteers. Secondly, we identified new biomarkers (in particular EEG and neuroimaging) for assessing the effect of new drugs. Finally, we improved the stratification strategy for inclusion of patients in clinical trials.
However, not all of our papers have been published yet. Some studies are still on-going and we have not analysed all the results. But we have started communicating our results in congresses on Alzheimer’s and we have published some of the papers. We have already established ourselves as a project which contributed to the knowledge of pathophysiology and pharmacology of the disease. And we will continue to deliver.
IMI Programme Office: How did the academic community benefit from being involved in this project?
Régis Bordet: We benefitted from international visibility and the network we formed with other academic and industry partners. The project officially ended, but we are continuing to collaborate and apply for new grants together.
It was very interesting to work with pharmaceutical companies, because their approach is sometimes quite different. From them, we learned new ways of working, which are more precise and more rigorous in terms of data follow-up.
IMI Programme Office: Jill, how will the industry benefit from participating in Pharma-Cog?
Jill Richardson: We shouldn’t underestimate the networking that happened not only between academia and industry but also between EFPIA companies. This enabled great debate in formulating a consensus on the utility of animal models, healthy volunteer studies and the various biomarkers used in AD research.
IMI Programme Office: What about the patients? How will they benefit?
Jill Richardson: In the long-term, if the Pharma-Cog biomarker matrix development is continued and the stratification of patients based on that matrix development is adopted by industry, it could lead to more efficient clinical trials. In the pharma industry, if you can do smaller trials and stratify the patients better, it will significantly increase the number of trials that can be conducted, rather than pinning all the hopes on one drug in a very large Phase II clinical study. Thanks to Pharma-Cog, we may have more efficient and more precise clinical trials in the future, which should enable faster development of new drugs for patients.
IMI Programme Office: Did you have any SME success stories within the project?
Jill Richardson: One of our partners, a French SME, developed a diagnostic kit for AD – a panel of inflammatory proteins which shows correlation with the worsening of the disease. They had already developed the panel before Pharma-Cog, but they were using the project to further validate it. They recently filed a patent application for it.
Régis Bordet: Another achievement of Pharma-Cog is that we have attracted an SME which didn’t take part in our project. They saw the results of Pharma-Cog and they asked me to help them develop their compound which could be very interesting for AD treatment. And we are using the study design and the biomarkers which we have identified in Pharma-Cog. The project is worth 3 million euros and has received support from the French government. By early 2019 we will know whether there is a sizeable effect of this compound on Alzheimer’s, and whether it is worth pursuing further in a clinical trial. Thanks to this cooperation, we will have a real-life demonstration that we have done in Pharma-Cog is useful for the development of new compounds for AD patients.
IMI Programme Office: Would it have been possible to achieve everything that you have achieved in this project without the public-private collaboration brought by IMI?
Régis Bordet: Without IMI, we would not have been able to develop this project – that is clear. Many of the academic teams didn’t work together before, and the contact with pharmaceutical companies would not have been of the same nature. In Pharma-Cog, we were working in a precompetitive space without any problems such as: this is my drug, this is not my drug and so on… Before developing a specific drug for Alzheimer’s, we need to have a global framework in which we can all work. And thanks to IMI, we developed results beyond the individual interest of each participant.
IMI Programme Office: Jill, what did you learn in your role as project coordinator?
Jill Richardson: Managing a 38 partner consortium was a great experience and I enjoyed working with the management team to prioritise and critique studies, and ensure the most efficient allocation of the budget. I would not hesitate to lead another public-private partnership but would be keen to be involved from the outset next time as I think some of the objectives of the project were a bit too ambitious in light of the time-frame and budget. I think focus is the single most important factor for success and the deliverables set out at the start of the project could have been more clearly defined to achieve such focus.
The experience of leading this project has increased my connections to the AD research network within Europe and allowed me to engage with many experts in technical fields that I have not previously worked on, e.g. EEG. It is clear that success for this type of public-private partnership is dependent on the passion, commitment and dedication of all participants and that was very evident for PharmaCog.
IMI Programme Office: Régis, what was it like to be the scientific coordinator?
Régis Bordet: Being a scientific coordinator of such a project gives you visibility and legitimacy in front your colleagues, but it is also very time-consuming. It is hard work, because you are responsible for the success or the failure of the project and that can make you anxious sometimes when there is a delay or a budget problem. It is not an easy life but it is a very interesting experience and I have learned a lot from it. I am the vice president of research at my university and I am sure that management of Pharma-Cog has also helped me make improvements in the management of the team at my university.