How to Optimise Your Biomarker Development Strategies

Kristof Vercruysse, Director Clinical Operations at Ablynx, speaks to Dr. Gabriele Dallmann, CEO of Pharmatching GmbH about Innovation in phase 1 clinical development and optimisation of biomarker development strategies. To listen to the podcast go to Troubleshooting Biomarker Development Strategies.

G Dallmann: Can you please introduce yourself with a brief overview of your current role?

K Vercruysse:
My name is Kristof Vercruysse and I’m responsible for the clinical operations department within Ablynx. I think in this position I’m quite lucky to be able to wear different hats because part of it is scientific, a big part of it is the responsibility of overseeing zero activities, and there is also a small part where some vendor management comes into play.

G Dallmann: You will speak in this conference on a very interesting topic and this is the RIPA and RICO predicting efficacy of the nanobody ALX-0081 in von Willebrand factor mediated thrombosis with special Phase One/Two analysis. You will give an overview on this nanobody and on the development of biomarkers, aspects such as Phase One healthy volunteer, Phase One BPCI patients and Phase One C Administration to Healthy Volunteers. This sounds really very interesting, and before I ask you a couple of questions related to the clinical development aspects, I wonder could you explain what RIPA and RICO are?

K Vercruysse: These two are the biomarkers that we used for development of our ALX-0081 compound and its ristocetin induced platelet activation or cofactor. The RIPA is on fresh blood whereas the RICO can be done on frozen blood.

G Dallmann: It’s a very current topic of great interest. Thisyear’s conference is subtitled with Benchmark: The latest strategies to prevent late stage failure and allow information, which decisions to be made during early clinical development. I would like to know how important is this for you, working as the Director of Clinical Operations at Ablynx, and what in particular is essential for your company in the coming 12 months?

K Vercruysse: It goes without saying that it is very important and as a Director of Clinical Operations I’m involved quite early in the development process. Also being part of a biotech company, we have to make information which decisions because every decision has an impact on the value of the company. This year we communicated to the outside world that we are planning three Phase One studies and one Phase Two study in 2011, so delivering on this promise is essential for the company.
G Dallmann: You are going to discuss, as mentioned already, a very, very interesting and current topic and that is how to develop biomarkers and biomarker development strategies. This is really of great importance for every clinical trial but, in your opinion, what are the critical success factors in this field and when is the optimal time to start a biomarker development?

K Vercruysse: Optimal timing, I would say as early as possible, and for us this means at the start of our development and target selection. The critical success factors should be that you can show activity early on in your development and also, additionally, show correlation between the biomarker and the disease that you are developing your compound in.

G Dallmann: Do you use biomarkers in every clinical development programme and, if yes, how do you make the decision on that?

K Vercruysse: Having biomarkers is one of the selection criteria for our target selection, but of course we need to be able to define what a biomarker really means. For some it’s the ability to be able to select the best patient population; for some it is the changes in safety laboratory measurements; for others it’s really showing the activity of the drug. So when we are talking about biomarkers, I think still a lot of definition needs to be considered.

G Dallmann:Do you have a real life example of how a biomarker has saved you time, cost or helped you make a go, no-go decision?

K Vercruysse: That’s what I’m going to present during the conference, of course. I think cohort escalation translation from preclinical into clinical, translation from healthy volunteers into patients – I think we have numerous examples here.

G Dallmann: Do you agree then that there is a trend towards increased needs to include patients already in Phase One studies and what do you think are the main challenges and solutions when using patients in Phase One compared to healthy volunteers?

K Vercruysse: I think, with all the knowledge that has been gathered during the past year, there is definitely a trend to go to patients faster. The majority of the compounds are being developed more against targets that are expressed in disease models and I think therefore it’s also better to go as early as possible into patients, but I think we also can’t lose track of the safety. The main challenges in these patient studies is, of course, the recruitment; especially the informed consent process is rather challenging, if you go for therapeutic areas where the patients are not at an end stage compared to some oncology studies. This is also something that I will elaborate a little bit more on during my presentation at the conference.

G Dallmann: You mentioned already the aspect of recruitment and can you still make comment on that in terms of what is the consequence of the acceleration of patient recruitment into early stage and late stage studies, such as in terms of number of centres, number of patients per centre, consistent management of quality and the control of KPIs and cost?

K Vercruysse:It depends, really, on what is the reason for the acceleration. I think you have to look at it case by case because sometimes it’s in exclusion criteria which are not strict enough, not enough patients presenting themselves at the different sites. I think also if you open additional sites this will, of course, have an impact on cost and control of KPIs, but something we must not forget is also the learning curve. Every site that you open, it’s also a little bit on quality, so starting a clinical trial test centre they have to go through this learning curve, especially in early stage patient trials. If you work with staggered cohorts, planning screening is very important and even more difficult if you have not the precise multiple country studies. But with current solutions like IVRS and many others, I think these are consequences that can be dealt with. I think emphasis on good planning before start of the study is very crucial.

G Dallmann: With all this experience and knowledge with the evolving nature of early development and trial design, where do you see Phase One studies in five years time?

K Vercruysse:More and more I get the feeling that the Phase One studies as we used to know them will disappear more and more and the adaptive designs have already had a big impact on Phase One as a whole. Planning and execution will have to be more flexible than ever and, to make a wild statement at the end, maybe we will no longer talking about Phase One or Phase Two or Phase Three studies, but some new definitions will present themselves.


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