Choosing the project

Chapter 5 Choosing the project



H P. Rang, R G. Hill



Introduction


In this chapter we discuss the various criteria that are applied when making the initial decision of whether or not to embark on a new drug discovery project. The point at which a project becomes formally recognized as a drug discovery project with a clear-cut aim of delivering a candidate molecule for development and the amount of managerial control that is exercised before and after this transition vary considerably from company to company. Some encourage – or at least allow – research scientists to pursue ideas under the general umbrella of ‘exploratory research’, whereas others control the research portfolio more tightly and discourage their scientists from straying off the straight and narrow path of a specific project. Generally, however, some room is left within the organization for exploratory research in the expectation that it will generate ideas for future drug discovery projects. When successful, this strategy results in research-led project proposals, which generally have the advantage of starting from proprietary knowledge and having a well-motivated and expert in-house team. Historically, such research-led drug discovery projects have produced many successful drugs, including β-blockers, ACE inhibitors, statins, tamoxifen and many others, but also many failures, for example prostanoid receptor ligands, which have found few clinical uses. Facing harder times, managements are now apt to dismiss such projects as ‘drugs in search of a disease’, so it is incumbent upon research teams to align their work, even in the early exploratory stage, as closely as possible with medical needs and the business objectives of the company, and to frame project proposals accordingly. Increasingly, research is becoming collaborative with large pharmaceutical companies partnering with small biotechnology companies or with academic groups.



Making the decision


The first, and perhaps the most important, decision in the life history of a drug discovery project is the decision to start. Imagine a group considering whether or not to climb a mountain. Strategically, they decide whether or not they want to get to the top of that particular mountain; technically, they decide whether there is a feasible route; and operationally they decide whether or not they have the wherewithal to accomplish the climb. In the context of a drug discovery project, the questions are:



• Should we do it? (strategic issues)


• Could we do it? (scientific and technical issues)


• Can we do it? (operational issues).


The main factors that need to be considered are summarized in Figure 5.1.


image

Fig. 5.1 Criteria for project selection.



Strategic issues


Strategic issues relate to the desirability of the project from the company’s perspective, reflecting its mission (a) to make a significant contribution to healthcare, and (b) to make a profit for its shareholders. These translate into assessments respectively of medical need and market potential.



Unmet medical need


Unmet medical need represents what many would regard as the most fundamental criterion to be satisfied when evaluating any drug discovery project, though defining and evaluating it objectively is far from straightforward. Of course there are common and serious diseases, such as many cancers, viral infections, neurodegenerative diseases, certain developmental abnormalities, etc., for which current treatments are non-existent or far from ideal, and these would be generally accepted as areas of high unmet need. Nevertheless, trying to rank potential drug discovery projects on this basis is full of difficulties, because it assumes that we can assess disease severity objectively, and somehow balance it against disease prevalence. Does a rare but catastrophic disease represent a greater or a lesser medical need than a common minor one? Is severity best measured in terms of reduced life expectancy, or level of disability and suffering? Does reducing the serious side effects of existing widely used and efficacious drugs (e.g. gastric bleeding with conventional non-steroidal anti-inflammatory drugs) meet a need that is more important than finding a therapy for a condition that was previously untreatable? Does public demand for baldness cures, antiwrinkle creams and other ‘lifestyle’ remedies constitute a medical need?


Assessing medical need is not simply a matter of asking customers what they would regard as ideal; this usually results in a product description which falls into the category of ‘a free drug, given once orally with no side effects, that cures the condition’. Nevertheless, this trite response can serve a useful purpose when determining the medical need for a new product: how closely do existing and future competitors approach this ideal? How big is the gap between the reality and the ideal, and would it be profitable to try and fill it? Using this type of ‘gap analysis’ we can ask ourselves the following questions:



• How close do we come to ‘free’? In other words, can we be more cost-effective?


• Compliance is important: a drug that is not taken cannot work. Once-daily oral dosing is convenient, but would a long-lasting injection be a better choice for some patients?


• If an oral drug exists, can it be improved, for example by changing the formulation?


• The reduction of side effects is an area where there is often a medical need. Do we have a strategy for improving the side-effect profile of existing drugs?


• Curing a condition or retarding disease progression is preferable to alleviating symptoms. Do we have a strategy for achieving this?



Market considerations


These overlap to some extent with unmet medical need, but focus particularly on assessing the likelihood that the revenue from sales will succeed in recouping the investment. Disease prevalence and severity, as discussed above, obviously affect sales volume and price. Other important factors include the extent to which the proposed compound is likely to be superior to drugs already on the market, and the marketing experience and reputation of the company in the particular disease area. The more innovative the project, the greater is the degree of uncertainty of such assessments. The market for ciclosporin, for example, was initially thought to be too small to justify its development – as transplant surgery was regarded as a highly specialized type of intervention that would never become commonplace – but in the end the drug itself gave a large boost to organ transplantation, and proved to be a blockbuster. There are also many examples of innovative and well-researched drugs that fail in development, or perform poorly in the marketplace, so creativity is not an infallible passport to success. Recognizing the uncertainty of market predictions in the early stages of an innovative project, companies generally avoid attaching much weight to these evaluations when judging which projects to support at the research stage. A case in point is the discovery of H2 receptor blockers for the treatment of peptic ulcer by James Black and his colleagues where throughout the project he was being told by his sales and marketing colleagues that there was no market for this type of product as the medical professional treated ulcers surgically. Fortunately the team persisted in its efforts and again the resulting drug, cimetidine, became a $1 billion per year blockbuster.



Company strategy and franchise


The current and planned franchise of a pharmaceutical company plays a large part in determining the broad disease areas, such as cancer, mental illness, cardiovascular disease, gastroenterology, etc., addressed by new projects, but will not influence the particular scientific approach that is taken. All companies specialize to a greater or lesser extent on particular disease areas, and this is reflected in their research organization and scientific recruitment policies. Biotechnology companies are more commonly focused on particular technologies and scientific approaches, such as drug delivery, genomics, growth factors, monoclonal antibodies, etc., rather than on particular disease areas. They are, therefore, more pragmatic about the potential therapeutic application of their discoveries, which will generally be licensed out at an appropriate stage for development by companies within whose franchise the application falls. In the biotech environment, strategic issues, therefore, tend to be involved more with science and technology than may be the case in larger pharmaceutical companies – a characteristic that is often appealing to research scientists.


The state of a company’s development pipeline, and its need to sustain a steady flow of new compounds entering the market, sometimes influences the selection of drug discovery projects. The company may, for example, need a product to replace one that is nearing the end of its patent life, or is losing out to competition, and it may endeavour to direct research to that end. In general, though, in the absence of an innovative scientific strategy such top-down commercially driven priorities often fail. A better, and quicker, solution to the commercial problem will often be to license in a partly developed compound with the required specification.


In general, the management of a pharmaceutical company needs to choose and explain which therapeutic areas it wishes to cover, and to communicate this effectively to the drug discovery research organization, but most will avoid placing too much emphasis on market analysis and commercial factors when it comes to selecting specific projects. This is partly because market analysis is at best a very imprecise business and the commercial environment can change rapidly, but also because success in the past has often come from exploiting unexpected scientific opportunities and building a marketing and commercial strategy on the basis of what is discovered, rather than the other way round. The interface between science and commerce is always somewhat turbulent.

Related posts:

  1. Intellectual property in drug discovery and development
  2. Clinical imaging in drug development
  3. Choosing the target
  4. The role of information, bioinformatics and genomics

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Oct 1, 2016 | Posted by in GENERAL SURGERY | Comments Off on Choosing the project

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