Andreas Persidis of Biovista talks to NGP about the transformational potential of drug repositioning.

NGP. Drug repositioning seems to be attracting increasing interest in the pharmaceutical world. Is there a real need for it?

Andreas Persidis. Drug repositioning has been attracting the interest of pharmaceutical and biotech companies for two reasons: commercial and scientific. On the commercial side, the simple truth is that company pipelines are not growing at the desired pace. At the same time, the return per dollar or euro spent in the lab has been steadily decreasing. Pharmaceuticals have been trying a number of tactics such as “light reformulations” that extend patent protection and company buyouts that instantly grow their pipelines with new compounds. These tactics, however, are proving less viable as regulatory bodies tighten their criteria and we begin to run out of companies to buy.

On the scientific side, the promise of certain technologies is not unfolding as hoped for. At the same time, we are all beginning to realise some of the limitations of our existing knowledge, not only at the disease, but also at the biology and drug mechanism levels. In this context, it makes sense to “milk the knowledge cow” by recombining our existing knowledge in as many new ways as possible, with the specific aim of identifying workable drug—therapeutic area correlations that have so far escaped our attention and screening systems. So, yes, in my opinion there is a real need for drug repositioning.

NGP. Is drug repositioning here to stay?

AP. I think drug repositioning is here to stay and eventually could even lead to the transformation of drug development as we currently know it. Drug repositioning represents a shift in the way we look at biology and develop drugs, by actively exploiting the interconnectivity of biological sub-systems and processes as well as the multi-faceted nature of disease mechanisms. The tools and methods that are currently developed with repositioning in mind, could however be applied to de novo compound discoveries, as well as to improving our understanding of biology itself. Then, there is a very sound financial argument that works in favour of repositioning. In certain circumstances repositioning can deliver results for 20 percent of the typical cost of bringing a new compound to phase II using traditional approaches.

Finally, there are efficiency reasons that make active repositioning a sensible strategy to follow. I think it is clear that every VP of clinical or business development wants to know all viable uses of the compounds at their disposal so as to maximise the exploitation potential of their company’s portfolio. This is not presently the case, and drug repositioning is one good way to address the issue.

NGP. In a drug repositioning context, what is the role of academia and of traditional drug development processes?

AP. By definition, drug repositioning works on existing knowledge – it reshuffles what we know about diseases and compounds in new and interesting ways that hopefully lead to new or better therapies. But many may hold that much that can be repositioned already has been. Here however, we need to remember that each new bit of knowledge interacts with many prior bits of knowledge, potentially creating opportunity for new discoveries.

If we look at each new discovery as a singular chunk of knowledge, then every single new chunk that is added to our existing collection of chunks (our entire body of biological and drug knowledge) creates thousands, if not millions, of new combinations to be explored. It is also clear that the clinical trials phases are here to stay for quite some time. Drug repositioning holds some significant promise to shorten and make less costly the development of drugs; it is clear, however, that traditional scientific discovery as currently practiced in academia will continue to play a significant role.

NGP. Is there a best way in which drug repositioning can be practiced?

AP. Drug repositioning is not a new idea. It has been happening since the early 1990s, mostly as a serendipitous process. in recent years, however, and as its value becomes more evident, a number of companies have developed tools to make the process more systematic. Most use mathematical or other models that by necessity make certain assumptions and may omit seemingly unrelated but probably relevant knowledge. They also tend to focus on the benefit side of the equation, i.e., finding the new application for the compound or drug. Some companies, such as Biovista, go a step further by simultaneously addressing the risk side of the equation, namely the adverse effects profile, making for much more balanced predictions of the clinical outcome of the repositioned drug.