Lab21 make it personal

In an age of personal computers, personal MP3 players and personal trainers, Lab21 say they have the key to personalised medicine

With a genome of 30,000 genes and an estimated 5 million single nucleotide polymorphisms, it is clear that there are endless genetic combinations that can affect an individual’s response to medicines. It seems that there is no such thing as an average patient.

“We are all different,” explains Dr Nick Kerton, CEO of Lab21, a new company set up to provide, among other things, phamacogenetic testing. “For example, if there were 2 versions of me, each slightly overweight for their height, and each with the same blue eyes, we could still have different responses to the same drug.”

This is not a new idea - as early as 1964 genetic variations in ethanol metabolism was noted - but it is one which has been slow to catch on with drug discovery companies and health care providers.

One size fits all
Traditional pharmacology has adopted the ‘one disease, one drug’ approach, but it is becoming increasingly apparent that this rather blunt edged tool is not working as well as it should. It is a sobering thought that the majority of drug therapies only work in 40-50% of cases. That was the well-publicised admission of Allen Roses, vice president of GlaxoSmithKline, and has been seen, not as a statement of defeat, but rather a call to arms for the scientists and clinicians involved in pharmacogenetics and personalised medicine.

Combining genetic insights with pharmaceutical knowledge, personalised medicine is based on the idea of using a patient's genotype as a factor in deciding on treatment options, capitalising on the differences in our DNA to give each patient the best chance of a successful therapy.

Get personal
At the core of personalised medicine is the idea that humans differ from one another in their reactions to drugs. This may be in the way they metabolise drugs, in the way the drugs actually operate within their bodies or the rates and extent to which the drugs are removed. The rapid advancements in molecular biology and the Human Genome Project have given researchers precise tools with which to dissect these differences, and to apply this knowledge to clinical treatment.

Indeed, matching patients to treatments by screening their genetic makeup has become the goal for those working towards personalised medicine. It is about putting patients into smaller, more predictable treatment groups than is currently possible. This means that specific treatments and therapeutics prescribed will be best suited for an individual's genotype.
Lab21 has such a goal. Set up in April this year, and bringing together high level drug discovery experience and a wide range of testing technologies, it provides drug discovery and clinical trials services to the pharma and biotech industries, and testing services to the NHS and private hospitals. Dr Nick Kerton said: “We believe that Lab21 has already made significant progress towards the goal of personalised healthcare. Our customers can benefit today from a unique portfolio of tests that allow the characterisation of a virus, the assessment of prospective drug candidates, and the understanding of potential resistance. In addition, we can genotype a trials population, assess their pharmacogenetics, or monitor patients undergoing therapy.”

They say that by testing each patient and detecting which variant of a disease they are suffering from they can then tell what treatment strategy the patient would benefit most from. “There are natural non-responders, who will not get the beneficial aspects of a given drug. Or there are subtle differences in someone’s genetic makeup that mean that they will respond differently.” Explains Dr Kerton. “It will also help to combat the hundreds of thousands of patients that die each year due to adverse drug reactions.”

Dr Nick Kerton, CEO of lab21 (right) Tony Ratcliffe,financial director (left)

It is fairly well recognised that a personal approach to medicine would reduce the risk of adverse drug reactions. The FDA now requires pharmacogenetic data to be included in submissions for new drug approval and clinicians and healthcare providers are also embracing the same molecular and pharmacogenetic tests. They expect that each individual patient journey will be safer, more effective and more cost efficient as a result of this new approach. Here, government is stepping in with, for example, the recent issue of UK guidelines that call for genetic testing to be used as a front-line test for the diagnosis of Cystic Fibrosis in babies.

Industry interest
Industries interest in the use of genetic testing to develop and prescribe drugs is relatively recent, but it has stimulated considerable investment on the part of pharmaceutical companies. One estimate is that somewhere between 10 and 20% of big pharmaceutical company research and development budgets are now directed towards genomics. However, some say that the old model of big pharma drug discovery will just not work effectively and many industry observers have said that the era of personalised medicine will be the end of the ‘blockbuster’ drug.

Undoubtedly economics will play a crucial role in how personalised medicine will develop. However, this is a complex issue as it could bring increased cost in some respects, and considerable savings in others. The advantages of large scale drug production will be lost when making drugs for smaller more specific populations. However a report from the Boston Consulting Group suggests that that the massive development cost of taking a drug from concept to market, around £500 million, could be reduced by 30% by personalised medicine.

The huge cost of clinical trials is another area that could be made more efficient. “It could be that drug tests at the clinical trial stage have failed because the population that have been selected were non-responders.” Explained Dr Kerton. By carefully monitoring the sample population of a clinical trial, respondent and non-respondent patients can be identified in advance and only those likely to benefit from the treatment enrolled into trials.

Challenges
The challenge now for the pharmacogeneticists is the implementation of personal medicine methods into the way health services are provided. “We can envisage the day when companies will offer doctors a diagnostic package enabling the doctor to do a test that will indicate if a drug will be valuable or not for an individual patient on the basis of certain genetic or physiological markers,” suggests Mike Ward, a life sciences specialist at the FBR International investment bank.

In the gamut of publicity that has surrounded personalised medicine some have pointed out that policy makers need to focus on the science and not the hype when considering the technology. In his recent book, The Politics of Personalised Medicine, Adam Hedgecoe of Sussex University suggests that a healthcare revolution based around pharmacogenetics “lies tantalisingly out of reach.”

However, with new genomic insights, companies like Lab21 may hold the key to personalised medicine’s promise of removing much of the uncertainty that surrounds current drug use - saving money, time and lives.

By Phil Prime

Case studies
One example where genetic variation can have important health implications is in the treatment of ADHD (attention-deficit/hyperactivity disorder).
Strattera (atomoxitine HCL) was approved by the FDA in November            2003 for the treatment of ADHD in children. The drug is well absorbed after oral administration and is metabolised by the cytochrome P450 2D6 (CYP2D6) enzyme pathway. The approved FDA label notes that genetic variation in this pathway means that CYP2D6 poor metabolisers have 5-fold higher peak concentrations of the drug in their blood; they take up to 5 times longer to eliminate the drug from the body and have a significantly increased chance of side effects. Clearly, knowing the CYP2D6 genetic profile of an individual will be important when prescribing this drug. This measurement is one of many that can be provided by Lab21.

It has been known for a long time that cancer is not the came in any two patients, even when they have the same type of cancer. Antigenics have produced a personalized vaccine, Oncophage, designed to treat cancer with the intent of minimizing side effects that is currently being evaluated in clinical trials. Based on proprietary heat shock protein technology, the Oncophage vaccine is designed to capture the particular cancer’s ‘fingerprint.’ This fingerprint contains unique antigens that are present only on that particular patient’s specific cancer cells. Injection of the vaccine is intended to stimulate the patient’s immune system to recognize and attack any cells bearing the specific cancer fingerprint.