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Widening the focus on innovations in cancer treatment

Published on 03/09/18 at 11:56am

Cancer treatment is making leaps and bounds, but public focus tends to gravitate towards the therapies themselves. Matt Fellows explores other areas where innovation is creating better patient outcomes.

Much has already been said on the advances of cancer treatment, and with much excitement. Rightfully so, as the rise of immuno-oncology blockbusters such as Bristol-Myers Squibb’s Opdivo and MSD’s Keytruda continue to dominate the market and rack up an ever-growing list of approved indications around the globe. The benefits they present to patients and the battle against cancer have transformed the treatment landscape, bringing progress that just didn’t seem possible years ago.

However, while these treatments are often at the centre of any discussion on innovations within the field of oncology, the conversation doesn’t end there. There is more to the story when it comes to the pursuit of better treatment outcomes, at both extreme ends of the clinical development journey.

At the near-end, much of the magic of innovation in the space is occurring in the preclinical stage. From technological advancements such as artificial intelligence and machine learning which leverage complex algorithms to analyse huge datasets and calculate drug targets to optimise development on a scale unattainable by human researchers, to the discovery of novel biomarkers which could broaden our understanding of the disease, the space is rife with new, progressive and effective tools and methodologies which feed into more robust drug development.

One such development, announced over the Summer this year, is GlaxoSmithKline’s new $300 million partnership with personal genomics and biotechnology firm 23andMe, a company which has made a very big name for itself in just over a decade by offering direct-to-consumer genetic testing kits. Through the service, users provide a saliva sample via a kit delivered by post, which is sent back to the lab, amplified, and tested against a wide array of variants. By using the service, consumers can gain insight into many aspects of their health and ancestry.

As the owner of what is currently the largest genetic database in the world, 23andMe is the ideal partner with which to forge a path ahead in genetics-based drug discovery, so its little wonder GSK moved to secure the partnership. The genetics company previously announced plans to move into drug development back in 2015 with the formation of a new therapeutics division and agreements to supply anonymous genetic data to major players such as Pfizer and Roche’s biotech arm Genentech.

By leveraging an estimated 80% of the firm’s existing database of genetic data from over five million customers, GSK hopes to galvanise its drug discovery and development efforts. Matt Nelson, Head of Genetics at the company, spoke to [Pharmafocus] to explain exactly how genetics-based approaches allow for more effective identification of ground-breaking drug targets.

“The more we understand about a disease, the better we will be at being able to find a way to prevent, treat or even cure it,” he remarked. “Genetic data can significantly improve our understanding of diseases, helping to explain why some people develop certain diseases whilst others don’t.  It can help us understand the disease pathway and how we might disrupt or target it, designing and developing more targeted medicines.

“We know drug targets that are backed by genetic information are approximately twice as likely to become a successful medicine, so understanding how a medicine is working can help us avoid unwanted side-effects and enhance the probability that the medicine will be effective.

“The advantage of basing early discovery decisions on human genetic insights is that these are directly relevant to human disease biology, whereas many cellular or animal models of disease may not accurately predict therapeutic effects.  However, this is not to say that every discovery decision must be backed by human genetic evidence or that other forms of evidence are not critical.”

It’s not a new school of thought, but only now is its potential ready to be fully reaped, as Nelson explains: “The benefits of using genetic data are well understood. However, it is only through significant scientific and technological advances in this area that have made it possible to generate it at a cost and scale that allows consumers to generate their own genetic information. Combined, this has created the unique 23andMe database, with billions of genetic and phenotypic data points that will improve our understanding of disease in a way that would not have been possible five years ago.”

So what does this mean for the new partnership, and the R&D efforts that it will spearhead?

”The collaboration combines 23andMe’s large-scale genetic resources and advanced data science skills, with the scientific and medical knowledge and commercialisation expertise of GSK,” Nelson continues. “We will work together to better understand key genetic effects on disease risk, severity, and progression, and to leverage that information to inform and direct R&D activities.

“The primary goal of the collaboration is to leverage 23andMe's genetic and phenotypic database to yield new diseases insights at a significant scale that will help identifying targets for drug discovery and development of medicines and possibly cures. But the ability to identify and invite people with a particular disease or risk factor, and in some cases specific genetic subgroups, to participate in studies that are relevant to them could significantly shorten recruitment and reduce clinical development timelines.”

It’s an exciting prospect, and GSK is keen to start work immediately. To this end, it has contributed its existing LRRK2 inhibitor programme as a potential treatment for Parkinson’s disease, hoping that 23andMe’s genetic database can quickly and efficiently identify carriers of a rare genetic variant to aid development – a process which would otherwise be costly and time-intensive. Under GSK’s estimations, there are around one million US patients with Parkinson’s disease, but only 135,000 LRRK2 G2019S carriers, and so just 10,000-15,000 such patients who are LRRK2 G2019S carriers; thus, clinical trial sites would need to genotype 100 Parkinson’s disease patients to find just one LRRK2 G2019S carrier.  23andMe’s database provides the solution, offering 10,000 re-contactable individuals with Parkinson’s disease, 3,000 re-contactable LRRK2 G2019S carriers, and 250 re-contactable LRRK2 G2019S carriers with the disease. The partnership means GSK can quickly recruit exactly who they need, and streamline development timelines far beyond what would be possible otherwise.

Early warnings

On the other end of the spectrum, after an oncology drug has successfully proven its efficacy in human trials and made it to market, lies a new challenge, and an endeavour that is arguably equally as crucial: the challenge of rapid cancer diagnosis. This is an ongoing battle and one in which much progress has already been hard-fought over the decades of educating the public, but, because treatment cannot solve the problem alone, there is still more work to be done. [Pharmafocus] caught up with Cancer Research UK’s Head of Early Diagnosis, Jodie Moffat, to get an accurate picture of where these efforts stand today, and why they’re so important.

“Cancer Research UK is making a huge investment towards increasing the amount of early detection research that goes on in the field of cancer,” she remarked. “Historically, there’s been relatively little happening in that space so we’re making a big effort to pull together the communities, build the expertise and fund some of these innovations.

“We’ve all seen those headlines of a blood test that can pick up early signs of cancer, and I think certainly there’s lots of research happening that’s investigating that; what biomarkers might we identify that we can use to catch early indicators earlier via a blood test? There’s also other things happening in terms of the imaging technology and volatile organic compounds – a whole range of different things. I think through the investment of CRUK we hope that we’ll be able to really identify this tech and innovation that will really help make a difference in the future, and then of course we just need to make sure the health services are in a position to implement them into practice.” 

Moffat identified a key tool in this effort: the multi-disciplinary diagnostic centre (MDC), a concept which began in Denmark and which CRUK, through a partnership with NHS England and Macmillan Cancer called Accelerate, Co-ordinate and Evaluate (ACE), is testing out in various locations across England.

“Some cancers have straightforward patterns of display; when the patient goes to a doctor and presents their symptoms, quite often the GP will know exactly what they’re suspicious of and will refer them on a particular route,” she explains. “Patients who present more generic symptoms such as weight loss or fatigue which don’t lend themselves to a particular route – they could be linked to a number of different diseases.

“If patients present those symptoms and the GP is suspicious that there might be something serious underlying them, they can refer the patient to an MDC and a problem-solving lens will be put to that patient and a number of tests can be performed to determine the cause of the symptoms. The idea is that you have hopefully removed the possibility of the patient being referred on the wrong route, that the patient doesn’t spend the same length of time as they would have done in other scenarios, and they reach a diagnosis and a resolution sooner than they would have done otherwise.”

Pushing for earlier diagnosis is a key element in the pursuit of better patient survivability which should not be forgotten; there is even a synergistic benefit to achieving earlier diagnosis which feeds into clinical development: it could help provide more participants with early-stage disease to participate in clinical trials. Moffat agrees: “There are still improvements that can be made to early-stage disease as well as late-stage disease, and so if you have a treatment that you want to trial in early-stage patients, then our efforts to diagnose patients earlier will give you a greater pool of patients from which to draw data. I think the opportunity is there.”

A two-pronged approach

It’s clear that both efforts in preclinical development and in more effective diagnosis are crucial in the treatment of cancer, but the important takeaway is that neither can be truly effective without the other.

“Earlier diagnosis and access to the best treatments go hand in hand. We don’t want to just diagnose patients earlier – that in itself isn’t going to make a difference,” Moffat notes. “It’s about the treatments that they get and the treatments that are available to them. We know that those more curative treatments like some radiotherapies and surgery are more common and more accessible to those patients who are diagnosed early – normally around Stage I or II; as that stage becomes more advanced, those treatments are just no longer an option for those patients. We see that play out in survival rates.

“I think we do actually have to delve a bit deeper into the data and have a look at where that need lies. Where do we find that we’ve got lots of patients diagnosed at a late stage? Lung cancer, colorectal cancer, prostate cancer – these are all areas where we’re getting really significant numbers of patients diagnosed with late-stage disease each year, and the survival that they have is really poor at those stages. There’s a huge opportunity and a huge need there.

“There’s also a lot we need to do around some of the treatments for patients. Lung is another example whereby not only do we need to get better at diagnosing that cancer earlier, but we also need to do better with treatment because when you look at the survival that patients – even with Stage II or III – have compared to some of the other cancer types, it’s much poorer. So there’s definitely room to improve those rates through those treatment options. It’s not a black and white thing with one over the other; they need to go hand in hand, and we can use data to really help us focus our efforts accordingly.”

However, there’s a big challenge standing in the way.

“A key consideration is the impact of workforce on both securing early diagnosis and delivering treatment,” Moffat highlights. “The NHS is in really challenging times at the moment; we’ve got an ageing population, so even if we didn’t see any improvements in the way we’re delivering care, we would still see more demand for services. We’re really going to be challenged to deliver the sorts of outcomes we’d like to see and we won’t be able to meet the international outcomes we’re seeing in other comparable countries.

“There is definitely some scope for improvements to push for greater efficiency and capacity in the system, but that is not going to take us far enough and relieve the capacity that we need for this. Unfortunately you can’t get away from the fact that the government needs to really take this seriously, plan for the future, deliver what we need now and ensure that we have a workforce in place that’s fit to deliver the services that patients need.”

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