Introduction
introduction T
he challenges facing healthcare, especially in the developed world, are changing dramatically. Populations are ageing rapidly and, inevitably, there is a concomitant increase in the occurrence of degenerative diseases for which treatment has been mainly palliative. However, there is now significant interest in regenerative medicine which focuses on repairing, replacing or regenerating damaged cells. This ever-growing market is increasingly attracting the attention of the pharma and biotech sectors. The scale and nature of this interest is analysed in one of our articles. The authors point out, however, that there are still issues to be addressed. For example, venture capital investments in small and medium-sized companies in this area have been hard to come by. Potential investors are concerned about the long development times almost inevitably involved in bringing regenerative therapies to the market and, additionally, there is uncertainty about the attitudes of regulatory agencies and of reimbursement authorities in an area which is relatively new to them. Our authors report that an Alliance for Regulatory Medicine has been set up to bring together regulators, industry and other appropriate stakeholders with the objective of addressing regulatory issues.
There is an obvious potential for stem cells in regenerative medicine and in another of our articles there is a discussion on what is needed to bring this potential to reality. Advances are being, or need to be, made in the ability to grow such cells on large scale and to direct and control their differentiation. Although there is progress there is still much to do. As ever, we carry articles which suggest improvements which could result in reductions in the attrition rate during the drug development process. Clearly the identification of lead molecules which stand a maximum chance of success in negotiating that process is key. To that end there is increasing interest in three-dimensional (3D) cell culture models to be used in screening. These allow cells to grow and adapt to their environment in a way which more closely approximates that experienced by cells in living tissues. Our author describes some currently available technologies which enable 3D cell culture. Issues which need to be considered include cost, ease of use, application and reproducibility. Validation of the technology will be required before it is accepted for routine use in drug discovery but there appears to be a clear potential here.
Another author identifies epigenetic screening as being an area where there is increasing interest. Epigenetic mechanisms are defined as inheritable factors that regulate gene expression without changing the DNA sequence. The results of a survey are reported. They reveal that several vendors now offer screening tools and assays and there is now an expectation that there will be an increasing use of them in drug discovery programmes. We also carry another review, this one being concerned with current technologies for discovery and delivery of molecular diagnostic, prognostic and predictive tests. There is speculation on the direction in which this subject is heading and there is reference to advanced technologies and likely requirements.
R&D directors are constantly reviewing what to include in their pipelines and how to balance relatively high and low risk opportunities. Everyone would like to discover and develop a first in class blockbuster but they are few and far between. One of our authors argues that biologics should be included more than they usually are in R&D portfolios. In particular, he advocates the inclusion of so-called ‘biosuperiors’ which show significant advantages over earlier products but which can be developed relatively quickly against an already established biological target that has been validated in clinical trials.
Drug Discovery World Spring 2011
This matches rather well with another article which describes the benefits of drug repositioning (or reprofiling as it is sometimes called). The author states that from 2007-09, 30-40% of drugs or biologics that were approved or laun- ched for the first time in the US were either drugs repositioned for new indications, reformulations or new combinations of existing drugs. His- torically, these new uses have often been discovered by acc- ident rather than by
design. Our author argues that, especially with the new technologies now available, there should be a systematic evaluation of any drug or mechanism of action against any disease or adverse event. He lists the advantages which may accrue from such an approach. These may be financial in that the re-launch of a repositioned drug will be very much cheaper than the launch of a new drug. This in turn represents an increase in return on investment. There may also be out-licensing opportunities and it is possible that the repositioned drug may have significantly greater market potential than it had for its original indication. We are now, according to another author, in the post genomics era. In his opinion the process of drug discovery has remained much the same for the past 10 years whereas advances in genome sequencing have been exponential during that time. There are, therefore, now hundreds of new targets in cancer alone which could be pursued for new therapies. The limiting factor, he argues, is drug discovery economics and he goes on to discuss what should be done about that. The logical goal, in cancer again, is to provide personalised therapies and diagnostics and this has been embraced by the pharma industry, although development times may be long and costs high. Late stage development on commonly occurring cancers is likely to be where pharma concentrates its resources. Academia and industry should, however, be encouraged to perform research on the wide variety of rare cancer targets which are now presented to us.
Correction In the Winter 2010/11 issue of DDW (Volume 12 Issue 1) we ran an article on page 31 entitled ‘Induced Pluripotent Stem Cells – a Model for Transforming Drug Discovery’. The authors would like to state the following:
“The McNeish screen was done with mouse ES cells, not iPS cells. The authors apologise for the confusion. The objective was to highlight the potential power of screening stem cell-derived tissues for small molecule effectors.”
Dr Roger Brimblecombe PhD, DSc, FRCPath, FIBiol 7
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