Drug Development
The combination of specific financial advantages, coupled with the realignment of the risk profile of a pipeline that includes repositioned drugs, are the key reasons why pharmaceutical companies look to this strategy with vigorous interest. This is further sup- ported by the existence of business centres within certain pharmaceutical companies whose remit is to explore repositioning opportunities for drugs in their respective portfolios. Examples include Pfizer’s Indication Discovery Unit, Bayer Healthcare’s Common Mechanisms Research group, Novartis’ New Indications Discovery Unit and others that are not perhaps as formally organised as these specific cases. Interestingly, a repurposing angle has the potential to integrate well with the efforts of phar- maceutical companies to virtualise the development of selected groups of drugs in their pipeline, such as GSK’s virtual proof of concept (vPoC) unit, or with the efforts of these companies to out-license some of their assets as discussed previously.
Beyond financial sense, drug repositioning is often analysed in terms of its patent protection scenarios and possible inherent limitation because of off-label use of such drugs in their new indications. The recent example of Cephalon acquiring Bioassets Development Corporation (BDC) for the new-use rights to Enbrel, which BDC repositioned in sciatica via epidural delivery, addresses both of these points8. First, one can obtain very strong patent protection for a new use of an existing drug whose composition of matter patents are still running, if that new use is not covered and proven in the original patents. Second, by administering Enbrel epidurally, which is a different route of administration to the original use of Enbrel, off-label use of Enbrel is lessened signifi- cantly and becomes solely the risk and responsibility of the physician. Payers do not support off-label use and more importantly, off-label use is a practice that applies to all drugs, including ones that are not repo- sitioned. Repositioning does not increase the risk of off-label use. Also, when a drug is repositioned, it is always a good idea to include, if medically appropri- ate, a different dose, formulation or route of admin- istration as additional barriers.
Having established that drug repositioning makes significant commercial sense, it is important to turn our attention to the concept of novelty and innovation. The decreasing amount of novelty and innovation in pharmaceutical R&D is a major issue, and one that is discussed and analysed with intensity5. If drug repositioning is to be considered a valid strategy for maintaining and growing the effectiveness of a drug development pipeline as an investment vehicle, independently of the pipeline belonging to a large pharmaceutical company and
Drug Discovery World Spring 2011
the stakeholders being the millions of public share- holders, or the pipeline being that of a smaller pri- vate biotech and the stakeholders being its private investors and VCs, then it has to survive and flour- ish because it also makes a legitimate contribution to the generation of novel or unexpected ideas and product opportunities.
Biomedical research moves forward based on dif- ferent kinds of innovation. To date, the most fre- quently discussed ones fall in four major categories:
1. New tools to do things (these would be reagents to explore biological phenomena or new types of drugs, such as aptamers, chimeric proteins, pep- tidomimetics, multi-valent antibodies and others). 2. New ways to measure things (these would be techniques of scientific observation and measure- ment, including new visualisation methods, multi- plexed assays, real-time biological kinetics meas- urements and others), 3. New ‘things’ themselves (devices, including the use of new materials with novel properties). 4. New ways to handle and extract insights from experimental observations (including advances in bioinformatics, data integration, knowledge man- agement, artificial intelligence and others).
One can consider the development of gene cloning, the PCR reaction, PAGE electrophoresis, monoclonal antibodies and mass spectrometry as the all-time singular advances that have defined modern biomedical research now and in perpetu- ity, and that no further true innovation that has generated the same quantum leap in our under- standing of biology or the development of drugs has occurred since. And although this would be a fascinating debate, the key point is that without fundamental new biological knowledge, all of these wonderful advances are solutions in search of a problem to solve and would not have been possi- ble in the first place.
The key question is whether drug repositioning can usefully advance our knowledge of basic bio- logical mechanisms, helping us discover new biolo- gy that we can use to develop novel drugs, even though these drugs may have been used in other indications. Every other kind of innovation, including the specific examples listed above, is not only indispensable in this effort, but can only realise its full potential if it can produce new bio- logical insights that teach us something we did not know and with which we can use to do good. Drug repositioning by its very nature is probably one of the single most powerful tools we have in our research arsenal today to accelerate our discovery
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