On July 4th 2017, Professor Dame Sally Davies (Britain’s Chief Medical Officer) published her independent report, entitled ‘Generation Genome’. The report explored the current use of genomics in our health and care system, and how its potential may be developed. This report has caused quite a stir, calling for the NHS and UK biotech industry to do more by making whole genome sequencing standard practice within five years, starting with genome mapping for all cancer patients. The report has been welcomed by many, including Jeremy Hunt (Health Secretary), who said that it was crucial to “push the boundaries of modern science" for the benefit of NHS patients. Horizon are working at the forefront of this technology; driving the translation of genomic knowledge into tools and services designed to drive personalised medicine. We at Horizon are very pleased with the Generation Genome report and are highly supportive of its recommendations.
Perhaps the most daunting challenge facing the healthcare system is the management of limited resources alongside an ageing population. The solution may lie in the fact that most of the diseases associated with ageing, such as cancer and dementia, are driven by genomics. Through a deeper and more thorough understanding of the genetic drivers of disease and genetic features that are predictive of treatment success an era of truly personalised medicine can be ushered in.
What is happening now is a new gold rush is taking place where drugs are being designed to work specifically for smaller populations of patients with particular genetic features. The Holy Grail is to build sufficient understanding of all of the genetic predictors and drivers of disease to enable the development of drugs that are targeted to those predictors and drivers. Dame Sally’s report commented that this approach has the potential to remove the ‘trial and error’ approach typically applied in drug development, while bringing fewer side effects, quicker remission and huge cost savings to health care systems.
Genomics also holds the promise of completely transforming the way that medicines are developed. It currently costs, on average, more than £1.6bn to develop a drug, and takes approximately 14 years or more to reach the market. The majority of this is associated with the impact of failures; effort, time and resources spent on avenues of research and development that ultimately don’t lead to a therapeutic. However, by using knowledge of the genetic drivers of disease to create more focused drug development programmes, much of the risk can be stripped out, significantly lowering the cost of development and reducing timelines to as little as three to five years in some cases. And this isn’t a dream for the future, it’s happening now. For example, approximately 80% of AstraZeneca’s drug development programmes are matched to a genetic biomarker (100% for cancer medicines).
Linking drug development to the underlying genetic drivers of disease means that clinicians can perform genetic tests to determine which drugs or combinations of drugs are most likely to work for a given patient. Consider lung cancer. This isn’t a single disease, but is instead thousands of diseases that can be characterised into pools of patients based on their particular genetic features, which can inform not only how the disease is likely to progress, but also what their risk profile was prior to onset of the disease and how to most effectively treat it when it has started. If two individuals both have lung cancer, they may well have different genetic features underlying that disease, and so that if a clinician has a toolbox of drugs that cover all of these genetic features, they are then in a far better position to deploy the right drugs to treat that disease. This approach means that we are prescribed the right medicines for us as individuals and payors are paying for drugs with the highest probability of success, rather than a one size fits all approach. Everyone benefits: patients have better outcomes, taxpayers get a better return on health care investment, and pharmaceutical companies have a route to change their development model and make it more efficient.
Additionally, when you consider the total pharmacopeia available today, few drugs were developed with the genetic drivers of disease in mind. Now, the promise exists to reposition many of these drugs to the patient populations, often in new indications, where they can have the most impact. An excellent example is AstraZeneca’s drug Tagrisso, which targets a small subset of patients with non-small cell lung cancer. This was an existing drug that was repositioned to benefit a specific new patient population based on their genetics and through this targeted approach came to market for this indication in approximately three years.
A convergence of technologies and business models has enabled this golden age for genomics. As the cost of sequencing a genome has come down we now have a viable approach to address questions around the drivers of disease, however translating this information into meaningful tools has been another challenge.
What’s really lead to the phase change is that technologies like gene editing have emerged, allowing those genetic drivers to be recreated in the form of human cells. These cells have become incredibly important tools in the life sciences because, whether disease takes place at the genetic level or the protein level, the function or dysfunction ultimately takes place within cells. So, by examining what happens in cells you can gain important insights into how disease develops, how it differs between individuals, and what impact a potential new drug is likely to have.
Horizon sits at the epicentre of this gold rush, building cells that act as the picks and shovels underpinning this revolution in the life sciences. We perform gene manipulation to make changes to cells, engineering them so that they reflect disease in real patients, letting you have in effect a pair of patients in a test tube, one healthy, one with disease, who differ only in the genetics that you’re interested in that you think drive disease or predict disease onset or response to a drug. These cells are then deployed to prove the hypothesis regarding the genetic cause of disease and to help pharma companies develop the drugs to treat it.
The implications of this work are vast. Once we understand the genetic drivers of disease, even for rare disease, we can try to develop cures. Horizon is also active in this space, supporting biotech and pharma companies in the fight against rare diseases like severe combined immunodeficiency (bubble boy syndrome) or more common ones like cancer.
One application showing tremendous promise is cell therapy, where the cells of a patient can be removed from them, their genetic code edited to repair the disease, and then the cells are re-implanted back into the patient to treat the disease. Immunotherapy is another highly exciting area. Cancer cells differ from normal cells in the body and the immune system attacks them when it is able to recognise them. However, this seldom occurs. Immunotherapy aims to re-activate the immune system, modifying or painting targets on cancer cells so that the cancer cells are destroyed as if they were an invading organism. Horizon is very active in both of these areas.
Horizon’s models are helping to condense drug development programmes, helping to support the development of a new pharmacopeia or toolbox of drugs over the next 10–15 years that can be used to treat patients with all kinds of genetic background. The question then shifts to how do you make sure that you deliver those drugs to the right patient at the right time, and that’s what Dame Sally was referring to in her report.
This is where the next wave is emerging. Your Genetics play a large role in the onset of disease but it is not the only factor. The environment is also important - the classic nature versus nurture argument. However, we now know that these are not entirely separate as your environment plays a significant role in activating your genes.
If where you live, what you eat, or if you smoke can turn on genes or impact the development of disease, there is a significant opportunity to intervene. Genomic screening early in life can identify your risk factors, and then you have the opportunity to manage and actively monitor your lifestyle to reduce the risk of disease and to catch it early when it is most likely to be able to have a positive intervention based on matching that new drug toolbox to your particular genetics.
Given the enormous potential of linking genetics with drug discovery and diagnostics, it is unsurprising that personalised medicine consortia have been established that bring together industry, academia, government and payors, all looking to advance the space and to support more fast-track clinical trials. Indeed, Barack Obama, Senator at the time, was a big supporter and introduced his Precision Medicine Initiative to advance the space.
In the future, Dame Sally has imagined a health care system where sequencing your genome has become a routine part of healthcare, informing clinical decision making and driving healthier lifestyle choices. This will help to ensure that the NHS is well-positioned to provide the highest standards of care well into the future, tailored it to the individual. At Horizon, we are completely supportive of this vision, and we are proud to be at the forefront of making it a reality.
Dr. Darrin M Disley
July 14th ,2017