Dreams to Reality
Dr Roger Brimblecombe
The world of drug discovery five years from now
Dr Roger Brimblecombe; Consultant Editor Drug Discovery World
Insights 2015

As Consultant Editor to Drug Discovery World during the 15 years of its existence, I have read some 400+ articles which have proved to be good indicators of trends in the world of drug discovery, be they technical or organisational.

Some trends have not withstood the test of time but others have progressed and are likely to progress further during the next five years.

Many of them will be driven by the increasing momentum of the move towards more personalised medicine. The days of the ‘blockbuster’ and ‘one size fits all’ drugs are numbered. As I pointed out in the Introduction to the Spring 2015 number of DDW, there are indications in the UK that politicians of all the main parties are dissatisfied with the ‘unsustainable’ and ‘unaffordable’ current method of developing drugs and will encourage the move towards personalised medicine. How this encouragement will manifest itself remains to be seen.

Another consequence of the demise of the blockbuster is the increased willingness of even the larger companies to become interested in developing therapies for rare diseases with relatively small numbers of patients. This seems likely to continue as does the tendency for companies to concentrate their resources, including R&D, in fewer therapeutic areas. This is exemplified by the deal in which GSK swapped its cancer treatment division for the Novartis vaccine units. It would not be surprising if other similar arrangements emerged.

The relationship between the industry and academia has always been somewhat uncomfortable with academia being uneasy about getting involved in commerce and the industry having difficulties with the desire of academics to publish early thereby prejudicing acquisition of intellectual property rights. There are definite signs that this is changing and that the change is likely to accelerate in the next few years. Each party increasingly recognises that the other has something to offer and various imaginative collaborative arrangements are being put in place, including geographical proximity, eg the siting of the new AstraZeneca headquarters in Cambridge, UK, presumably to facilitate access to University departments.

As big pharma continues to reduce its R&D (especially R) capabilities, there will be increasing reliance on small companies to provide viable leads. Again the range and scope of deals being struck appear to be on the increase. Close geographical location is again playing a role with, for example, Pfizer establishing laboratories close to the biotech hubs in San Francisco, La Jolla and Boston.

On the technological front I assume that others contributing to this Supplement will deal in detail with technologies where they have specific expertise. However, a few general trends are apparent. One, which is linked to the desire for more precisely targeted drugs, is the increasingly diminishing enthusiasm for the ‘shotgun’ approach of high throughput screening of very large numbers of molecules in favour of a more targeted approach with smaller compound libraries being subjected to high content screening and being tested in more physiologically relevant models. By 2020 it seems probable that enormous chemical libraries containing many thousand compounds will be a thing of the past. This, incidentally, will reduce the ever-increasing problems in managing and extracting relevant information from such libraries.

Another trend, representing a return to a practice which was popular, without being remarkably successful, several years ago, is the increased activity in what is now called Drug Repositioning and Rescue (NRPx) – it used to be referred to as New Drugs for Old! The advantage now, as it was then, is obvious in that many of the early hurdles (unexpected toxicity, unsatisfactory DMPK, etc,) will have been cleared. The attrition rate should, therefore, be lower and the development cost and time much lower than they would be for taking a drug into development ab initio. Advocates of this approach claim that it is ‘vibrant and growing year on year’ and that it is proving to be very successful. It may well, therefore, feature prominently in the next five years The therapeutic areas still demanding attention because of serious unmet clinical needs do not seem to have changed greatly over the last five, or even 10, years. Three such areas are dementia, cancer and antibiotic resistance and it will be extremely interesting to review them again at the end of the next five years to see what progress has been made.

There is still no cure for Alzheimer’s disease or the other dementias which are steadily increasing with the changing demographics worldwide. At best drug therapy can only temporarily delay or alleviate some of the symptoms and despite the billions of dollars which have been spent on R&D in this field nothing offering real therapeutic advance appears to have emerged or looks likely to do so in the reasonably near future. The amount of effort being devoted to this area by many of the large companies seems to have reduced markedly but, contrary to one of my statements above, a success here would almost certainly be a record breaking blockbuster. The incentive must be there for governments to encourage and support work in this area. An estimate in 2010/11 was that the economic burden of Alzheimer’s disease in the US alone was $216 billion and these numbers are presumably much larger now.

There has undoubtedly been progress in the treatment of cancer. Survival rates in the UK, for example, have doubled over the last 40 years and we can look forward with some optimism to accelerated progress over the next five years. Immunotherapy appears to offer great promise and recent results in malignant melanoma, for example, have attracted considerable attention, not least in the lay press in the UK. Cancer is an area where personalised medicine will certainly play a significant role with therapies being targeted to meet the patient’s specific needs by identifying biomarkers to point to the best treatment regime. The prediction here must be that in five years’ time cancer survival rates will have improved markedly.

A third area of considerable concern is the increasing problem of antibiotic-resistant organisms. No significant new class of antibiotics has emerged for a long time. This is presumably due, in part at least, to the difficulties inherent in discovering such drugs, but also to the fact that they do not provide a good return on R&D investment. Because of the significant impact on public health of this resistance this again appears to be an area crying out for governmental support. Whether this will occur in the next five years is by no means certain.

So, while steady progress is being made in some areas of drug discovery and some things foreshadowed in the 2010 supplement have come to pass, others have not. There have been few, if any, ‘eureka moments’ providing spectacular breakthroughs. Indications at the moment are that the same will be true if in 2020 there is another ‘semidecennial’ review. An exception may lie in the cancer therapy area where recent results are very exciting.