Part one: from biomarkers to biosensors

“Ask your doctor if this is right for you.”
 
Eighteen years after this refrain appeared in the United States upon the legalisation of direct-to-consumer healthcare advertising, it is starting to show its age. Today, fewer and fewer patients passively accept physicians’ advice.
 
Patients are increasingly active, informed consumers entering clinics armed with research and opinions about their healthcare options. They desire data on similar patients while calculating the benefits and risks of their choices. They ask, "Will this treatment work for me?" and "Which option offers the best value?"

To the patient–consumer, "precision medicine" represents the ideal standard of care: the individualised, evidence-based treatment that provides the best opportunity for a positive outcome. This desire for evidence of a treatment’s relevance, in conjunction with evolving pressures for clinicians and payers, has fuelled the meteoric success of genomic tests and targeted oncologics.

Indeed, the patient–consumer’s demands complement other shifts in the healthcare ecosystem, such as payers’ search for evidence to rationally constrain costs, clinicians’ struggle to retain profitability under payment reform, and regulators’ modernisation of approval mechanisms. Stratifying populations based on efficacy and risk factors not only helps to influence patients, but also to generate synergies that enhance overall commercial success.

In this new era of opportunity, genomics is one of the approaches available to sponsors to stratify patient populations in relevant ways. There are a myriad of strategies emerging, from novel classes of biomarkers to new instruments for collecting real-world evidence.

Thus, this multi-part series will survey the changing gamut of options for developing precision medicines, devices, and diagnostics—beginning with emerging biomarker strategies. Subsequently, this series will explore patient preference instruments that are creating new paths to regulatory approval, companion apps that are unlocking new value in highly scalable ways, and a convergence of technologies that represent a new model for clinical development.

 

From Biomarkers to Biosensors

The genomic testing methodologies for targeted oncologics that rocketed the term “precision medicine” into the public’s vocabulary are but the tip of the iceberg for biomarker-based strategies to identify relevant patient subpopulations.

In oncology, a second revolution aims to deliver more timely and comprehensive answers to cancer patients than possible through the first generation of companion diagnostics and laboratory developed tests.

One disruptive change is how and when patient samples are drawn. The first-generation tests guided treatment decisions based on tissue that was surgically biopsied from early tumours. However, after rounds of treatment, tumours are likely to evolve to resist prescribed therapies. As samples from the early tumour less accurately reflect the current state of the patient’s disease, the latest tests increasingly exploit non-invasive blood draws to provide physicians and patients with clearer options on a regular, perhaps even monthly, basis.

Additionally, these emerging liquid biopsy-based tests generally assess new classes of biomarkers, including cell-free tumour DNA, exosomes, and individually-analysed circulating tumour cells. Some tests examine not only genomic markers, but also proteomic markers, which may provide greater insight into disease phenotype than mutational status alone. Choosing the appropriate testing methodology is a nuanced affair; technologies’ relevance varies depending on the indication, disease stage, and the exact questions companies seek to answer for patients and clinicians.

A third major shift may extend from a deeper appreciation of cancer as a heterogeneous disease that is driven by multiple subclonal species of tumour cells. As patients and oncologists seek to prioritise and treat multiple disease drivers simultaneously, they may well force change in how both diagnostics and drugs are prescribed. That is, demand may wane for companion diagnostics that inform the selection of a single drug and demand may rise for larger panels that assess the relevancy of many drugs at once.

Furthermore, the data that emerges from the development of these diagnostics may then support the rational prescription of oncologics as combination therapies, mirroring the advent of HIV cocktail therapy in the 1990’s.
 
Outside of oncology, however, genomic testing is generally less prevalent, but that has not arrested the progression of precision medicine.

For cardiology, this is particularly true. A wave of new wearable sensors means that cardiology and other fields are not void of biomarkers to offer patients evidence-based, tailored treatments. For example, wearable sensors such as the ZIO Patch from iRythm Technologies and the AliveCor Mobile ECG allow continuous monitoring of cardiac status for more customised care.

Data from the sensors helps to reduce hospital visits, detect and respond to adverse events in real time, and provide a plethora of data and ancillary events of significant R&D value. Additionally, as cardiovascular conditions can span many years and patients often endure long-term trials of various medications to find an efficacious treatment, the ability to detect early efficacy signatures would provide marked advantages for patients.

 

Looking Ahead

Sponsors have a plethora of biomarker-based diagnostic options available to stratify patients for both response and risk. However, beyond biomarkers, there are numerous ways to deliver on the promise of precision medicine’s higher standard of personalised care and value.

The next instalment of this series will examine the patient preference instruments that not only provide meaningful guidance to patients, but also are creating new paths to regulatory approval.