Why Pharmacogenetics Matters

'It is an unfortunate fact that medicines are currently not as effective as they could be in an average of around 50% of patients, and in certain indications the success rate is even lower. This is why Roche is systematically pursuing personalised medicine'1

'Biotech/pharma and personalized medicine manufacturers who are early adopters of personalized medicine stand to receive significant ROI as highly effective targeted therapies displace traditional therapies'2

'To support the patient recruitment and multi-center trial requirements for more targeted study populations, companies may begin to develop research and information collaboratives with affiliates, academic medical centers and research organisations'2

^{1. Severin Sachwan, CEO, Roche (Burrill & Co Biotech 2009 - Life Science: Navigating the Sea Change)}

^{2. Deloitte Centre for Health Solutions}

^{What is pharmacogenetics?}

Pharmacogenetics is the study of how our genetic make-up affects the way in which we metabolise and respond to drugs. As a result, it is expected to play a key role in the future of drug development and healthcare delivery as the industry faces increasing pressure to replenish its pipeline, improve drug safety, and deliver cost-effective medicines. In its 2009 Global Biotechnology Report, Ernst & Young has speculated that with ‘the use of biomarkers to identify promising targets upfront, personalised medicine will also make early stages of the value chain – research and early development – more valuable’ .

By using genetic data to influence drug development and patient treatment, pharmacogenetics is an example of translational medicine in action - the movement of science from the bench to the bedside.

^{There is an increasing appreciation of the importance of pharmacogenetics in the drug development process, as evidenced by the level of investment in it by companies in the pharmaceutical and biotechnology sectors. Key players are, via collaboration and M&A activity, ensuring that they have access to the expertise needed. In addition, the FDA and the EMEA have recognised its importance in their Critical Path Initiative and Road Map respectively - http://www.fda.gov/ScienceResearch/SpecialTopics/CriticalPathInitiative, http://www.ema.europa.eu}

^{The growing number of genetic discoveries can only enhance this potential.}

By combining its access to genetic expertise with strategic advice on the application of pharmacogenetics in drug development, London Genetics can help companies meet this need for smarter, faster and safer drug development. Pharmacogenetics is part of the drug development puzzle.

 

How can pharmacogenetics add value across the R&D chain?

Pharmacogenetics can add value in the following areas:

• Providing an increased understanding of drug response profile and therefore confidence in a positive efficacy signal; which can be particularly important at the proof-of-concept stage;

• Identifying patient subpopulations which respond best and with the least side-effects to a given development compound or marketed drug. This leads to more effective and efficient clinical trials, resulting in improved pipeline productivity. Safety concerns have lead to some high-profile and costly marketed drug withdrawals in recent years. As well as leading to increased costs and loss of revenues and shareholder value for the companies involved, there has also been an impact on the industry’s reputation, and an increased regulatory focus on the safety of medicines. This been exemplified by an FDA Guidance for Industry in December 2008. In ‘Diabetes Mellitus – Evaluating Cardiovascular Risk in New Antidiabetic Therapies to Treat Type 2 Diabetes (Dec 2008)’  it discussed various issues such as ‘how to demonstrate that a new therapy.....is not associated with unacceptable increase in cardiovascular risk’, and that safety concerns were to be addressed during drug development. By identifying those patients whose genetic make-up means that they will experience side-effects when given certain drugs, the use of pharmacogenetics can help improve safety.

• Strengthening submissions for regulatory approval;

• Generating data which supports cost-effectiveness claims, leading to increased uptake and market share. This is an important consideration in this era of constrained healthcare budgets, particularly since severe side-effects can lead to significant hospitalisation costs. Various bodies are undertaking studies looking at the cost-effectiveness implications of prescribing based on genetic make-up. It is increasingly recognised within the biopharmaceutical industry that globally the payers will only pay for cost-effective drugs. In its Pharma 2020: Challenging business models. Which path will you take?, PriceWaterhouse Coopers believes that demand for personalised medicine is increasing , and payers are starting to pay for performance, outcomes and value for money.
  

• Via post-market surveillance, improving use of existing and recently launched drugs;

• Providing opportunities for lifecycle management.

Pharmacogenetics case study – warfarin

The widely used generic anticoagulant warfarin illustrates many of the ways in which pharmacogenetics can add value in the biopharmaceutical industry. For this drug, metabolism is affected by genetic variation among other factors. Getting dosing right is difficult and risks are high, since underdose can lead to strokes and overdose to bleeding, for example in the gut or brain. It estimates that genetic testing could prevent 85,000 serious bleeds and 17,000 strokes a year, leading to healthcare savings of $1bn per annum.

As a response to this, tests for warfarin-metabolising genes are being developed. The drug label, which was first modified in 2007, was updated for a third time in January 2010 to provide information on how specific genetic variants may influence a patient’s response. In Europe, the EU-PACT study is looking at the effect of gene-based dosing on 2000 patients. This study is taking place across eight centres, including some of the academic founding partners of London Genetics. Following work by the International Warfarin Pharmacogenetics Consortium, which developed an algorithm with the potential to help doctors prescribe the optimal warfarin dose, the NIH has started a large clinical trial to test whether gene-based dosing leads to optimal outcomes. It will involve 1200 patients and report in 2012. Backing up these trials, in March it was announced that a Medco Research Institute/Mayo Clinic real-world study had shown that when genetic data was available to warfarin-prescribing doctors, hospitalisations due to bleeding fell by nearly a third.

For this well-established generic, pharmacogenetics is enabling it to be prescribed in a more cost-effective and safe way, with significant impact on the product’s lifecycle expectations. The point to note here is that not only do these studies show how pharmacogenetics can inform increasingly safe treatment of patients, but also effective patient treatment. The other upside for the pharma companies involved may well be increased revenues from a boost in confidence about warfarin prescription.