Could virtual modelling offer pharma firms the tools to advance drug r&d? PriceWaterhouseCoopers examines the drivers reshaping the industry
The pharma sector needs to radically overhaul its r&d practices and innovate in its delivery of medicines if it expects to meet the burgeoning demands of future disease treatment.
With global life expectancy on the increase, the burden of chronic disease soaring and demand rising for treatments for specialist or more complex diseases, there is greater need for the development of drugs that treat disease symptoms cost effectively .
One way of achieving this is through greater understanding of the human body at a molecular level and with pharma companies gaining a better grasp of the functional changes arising from disease.
predicitive modelling
According to a report published by PriceWaterhouseCoopers on the future of the pharmaceutical industry by 2020, only 11% of the molecules that enter pre-clinical development reach the market.1 And, generally, companies begin testing a specific target with a particular molecule in humans only in Phase II of clinical trials. Considering that, according to the Tufts Center for the Study of Drug Development, the average bill for producing a new medicine is US$868m (Euro 549m) and the average cost of conducting the r&d is $454m ( €287m) per product, pharma companies cannot really afford wide margins of error.
The report - "Pharma 2020: Virtual R&D Which path will you take?" - recommends using more specific molecular details to build predictive models and more accurate information that can drive the development of suitable medicines. One example is the development of a diabetic virtual mouse model created through a partnership between The American Diabetes Association and US biopharma company Entelos. The two organisations are using the mouse to study cures for Type 1 diabetes. The model is based on years of data from experiments on real animals but virtual animals could be created for any species for which there is enough data.
Already, methodology such as predictive biosimulation is increasingly playing a role in the r&d process, with scientists at University College in London using computer modelling to simulate the efficacy of an HIV treatment in blocking one of the key proteins used by the virus.
The report recommends the uptake of a more predictive way of testing molecules before they go into man. There is also a suggestion that with the advent of virtual patients, it will be possible to "screen" candidates in a digital representation of the human body, which can be adjusted to reflect common genetic variations and disease traits, such as a weakened cardiovascular system.
"Although the "birth" of virtual man is still years off, it is likely that the next stage is semantic technologies and computer-aided molecule design," the report states. "As the pharma industry waits for the "virtual man model" it can make improvements on how it conducts research. One way is by paying more attention to validating in vivo disease models and making them more predictive by using products with proven clinical efficacy to test them."
There is also an assumption that these scientific and technological advances will ultimately render the current model of development, which includes the four distinct phases of clinical testing, obsolete. Greater understanding of how the body behaves on a molecular level and a much better way of monitoring patients will allow pharma companies to re-haul their clinical trial designs, thus reducing the number of studies they perform and the number of patients on whom new medicines are tested.
"The aim is that pharma directs its efforts more productively," states the report. "As well as having to ensure that new molecules are safe and efficacious, it will have to provide value for money."
rewarding innovators
A small yet significant point is that they believe there is a better way of stimulating genuine innovation and that should come from rewarding scientists for what they do and not what the company does. So, for example, GSK has overhauled its incentive scheme and now pays its researchers a bonus only when a candidate molecule reaches the proof-of-concept stage or when they solve major problems.
The aim is to encourage researchers to focus on creating compounds that have a real chance of success and it strengthens the links between the research and development functions.
Other factors driving sector change is an increasing cautiousness from regulators to approve innovative medicines in the wake of drug scandals such as Vioxx. Many governments are also beginning to focus on prevention, rather than treatment. And while, on the one hand, such a shift can be viewed as prohibitive to pharma business, the report suggests that this trend can become an enabling force for industry to enter into the realm of health management.
Increasingly, patients are taking control of their own health management and the "self-medication sector" continues to be boosted by a growth in the number of prescription products attaining over-the-counter status. These trends leave the path open for pharma sector to "cash in" on the shift. However, the industry must be willing to rebuild its image and show the public and healthcare professionals that it has their best interests at heart.
Reference
1. CMR International survey of 29 pharma firms,1998, in PARALEX¢s Pharmaceutical R&D Statistical Sourcebook (2001).