Insight

Liquid Biopsy – What’s real and what’s hype?

KPMG perspective on this innovative technology

Alasdair Milton, PhD

Alasdair Milton, PhD

Managing Director, Healthcare and Life Sciences Strategy, KPMG US

+1 617-988-5419

Puja Ghelani

Puja Ghelani

Director Advisory, Strategy - PDT, KPMG US

+1 918-845-2389

Kristin C. Pothier

Kristin C. Pothier

Global and National Leader, HCLS Strategy, KPMG LLP

+1 617 549 2779

Fast facts:

The market is as bullish as ever on liquid biopsy and the opportunities this technology represents to stakeholders across life sciences, but what’s real and what’s hype?

  • R&D advancements and FDA approvals continue to drive market enthusiasm
  • Deal activity and investments are high, with 2021 acquisition revenue multiples ranging anywhere from 26x to 154x
  • Public investment continues to grow, for example, the UK’s Department of Health and Social Care partnership with Grail to do 165K liquid biopsy tests over the next few years as part of its established population genomics program, Genome UK
  • KPMG proprietary Precision Medicine Insights database highlights an increase in anticipated use as Oncologists expect to increase treatment with targeted therapies
  • While analysts estimate the global addressable market size to be $70-100B across the diagnostic continuum from screening and diagnosis to treatment selection and ongoing monitoring, current market value (based on revenue generated from liquid biopsy) is likely in the range of $0.7-$2.3B at this time—highlighting that there’s a long way to go before the technology is widely adopted in clinical practice
  • Indeed, latest ESMO guidelines published in early-July 2022 highlights liquid biopsy as standard-of-care for genotyping and treatment selection in many advanced cancers, but cautions that “lack of evidence of utility prevents a recommendation to incorporate ctDNA assays for other possible purposes like screening, molecular residual disease assessment, molecular relapse monitoring and early assessment of treatment response”

 

Key takeaways

While it holds much future promise, the path to unlocking the full market potential of liquid biopsy is not necessarily clear to stakeholders such as pharma and biotech, diagnostics companies, and healthcare providers. We believe that:

  
  

Pharma and biotech must invest in use beyond treatment selection

  
  

Diagnostics manufacturers and labs must continue to focus on test quality and clinical utility

  
  

Healthcare providers must take a more active role in driving adoption

 

Pharma and Biotech: Invest in applications of liquid biopsy to expand from mostly treatment selection (including CDx) to include recurrence monitoring, specifically focusing on MRD (minimal residual disease).

A small number of tumor cells can remain in the body after a “curative-intent” treatment, driving relapse or recurring disease, either locally or through distant metastases. This is MRD. Due to the microscopic nature of the residual tumor cells, detection is particularly challenging and well-suited for liquid biopsy, which can detect circulating tumor DNA (ctDNA), circulating tumor cells (CTC), or tumor specific microRNA.

With its advantages around non-invasiveness and quick turnaround time, liquid biopsies and improved MRD testing can be particularly useful in investigational trials. Liquid biopsy can be used to complement tissue profiling and patient selection, potentially resulting in faster identification of responders, improved efficacy outcomes, and more cost-efficient trials. With additional investment and clinical evidence, liquid biopsy can transition from its current role as a supplementary testing tool to a key cog in the care continuum.

Pharma and biotech must continue to explore the application of liquid biopsy in investigational trials for MRD monitoring and invest in programs that drive clinical evidence generation to expand the use of these tests beyond treatment selection.

An increasing number of liquid biopsy tests such as Guardant Health’s Guardant360 CDx, Foundation Medicine’s FoundationOne CDx, and Menarini Silicon Biosystem’s CELLSEARCH are being used across many parts of the oncology care continuum.



1. Screening: 
Identify potential cancer risk early among healthy individuals



2. Risk stratification: 
Identify populations who are at higher risk of developing cancer



3. Diagnosis: 
Definitively diagnose cancer



4. Staging & Prognosis: 
Determine stage of disease and associated prognostic information



5. Therapy selection: 
Determine applicability of a therapeutic drug to a specific patient



6. Treatment monitoring: 
Measure a patient’s response to treatment and/or treatment efficacy and/or side effect



7. Recurrence monitoring: 
Monitor recurrence in those who are in or have completed treatment, or previously diagnosed with cancer


Screening

   
  • Identify potential cancer risk early among healthy individuals
  • E.g., PSA for prostate cancer, mammogram for breast cancer, pan-cancer screening (e.g., Grail Galleri)


Risk Stratification

   
  • Identify populations who are at higher risk and who should be considered for diagnostic testing
  • E.g., Percepta Nasal Swab to more accurately assess risk in patients with lung nodules


Diagnosis

   
  • Definitively diagnose a patient for a condition
  • E.g., skin biopsy to diagnose melanoma


Staging &
Prognosis

  • Determine stage of disease and associated prognostic information
  • E.g., imaging tests and tissue biopsy to identify stage of lung cancer during initial diagnosis


Therapy Selection

   
  • Determine applicability of a therapeutic drug to a specific patient
  • E.g., Cobas EGFR Test v2 to select for treatment with Iressa, Gilotrif, Tagrisso, Vizimpro etc. in NSCLC


Treatment
Monitoring

  • Measure a patient’s response to treatment and/or treatment efficacy and/or side effects
  • E.g., blood test to monitor nephrotoxicity of immunosuppressive drugs such as cyclosporine


Recurrence
Monitoring

  • Monitor recurrence in those who are in or have completed treatment, or previously diagnosed with cancer
  • E.g., PET/CT scan to assess suspected recurrent breast cancer

Illustrative, not exhaustive

 

Diagnostics Manufacturers and Labs: Improve test quality through new avenues and focus on conveying clinical utility at key treatment decision-points outside of therapy selection

By exploring alternative technologies that test for new targets such as RNA and proteins (instead of ctDNA, which has been a primary focus of the market), Dx manufacturers and labs may be able to improve test accuracy, an issue that has plagued this technology since its discovery many decades ago.

Additionally, market value has largely been concentrated in treatment selection, where tissue is often preferred if available – improving test quality to expand application across the diagnostic continuum, particularly for monitoring, early screening and risk stratification, will be particularly beneficial in unlocking market potential.

Tumor-agnostic testing for therapy selection seems to be an idealistic ambition at this time, but as advances in tumor agnostic therapies continue to drive innovation in the biopharma industry, with updated approval processes at both the FDA and EMA that support this innovation, Dx companies need to follow suit and pave the way with tumor agnostic testing – better liquid biopsy tests would lend itself well to this purpose.

While there are a few large liquid biopsy panels for therapy selection on the market, companies that offer smaller, more targeted panels are carving out a niche for themselves and getting adopted by clinicians. This also addresses the reimbursement challenges that are associated with testing everything under the sun as payors establish high standards for RWE on overall cost effectiveness.

While specialty labs (e.g., Grail, FoundationOne) have taken a lead role in driving research and development of marketed liquid biopsy tests, hospital and reference labs can play a supporting role in accelerating market expansion by mirroring the investment in specialized molecular pathology and NGS testing capabilities which are foundational to liquid biopsy LDT proliferation. This proliferation would then drive clinical and real world evidence (RWE) generation and improve test availability once validated. 

Diagnostic manufacturers and labs must continue to innovate and gather data demonstrating the clinical utility of liquid biopsy tests at different points across the care continuum while also focusing on tailoring solutions to the specific unmet needs for oncology indications where possible.

Increasing use of targeted therapies will continue to help drive an increased patient pool size for LBx testing in therapy selection and recurrence monitoring, areas that are seeing growing LBx uptake.

Providers expect to increase the use of single and  combination targeted / IO therapy 5 years from today…

Percentage of Patients treated by Therapy Type (% of 100)

Q: What percent of your actively treated cancer patients by stage receive the following treatments? US, Canada, EU5 Oncologists (n=142)

Note(s): 1. With or without surgery. Across Stage 1-4 patients and not weighted based on volume of patients in Stage 1-4; 2. Immunotherapy; 3. IO = Immunotherapy

…which will drive more LBx testing for treatment selection and recurrence monitoring

Oncologist LBx utilization, by Continuum Area (1 – 5 scale)

Q: Across the diagnostic continuum, to what extent are you utilizing liquid biopsy today? How do you expect that to change in 5 years vs. today? US, Canada, EU5 Oncologists (n=142)

Legend: (Scale of 1-5)
1 – Don't Use; 5 – Always Use


Source(s): KPMG Precision Medicine Insights database; NIH
 

Healthcare providers: Take a more active role in driving adoption to help address fundamental barriers to broader usage for both treatment selection and MRD monitoring, including lack of reimbursement and clinical evidence

Use of liquid biopsy testing beyond therapy selection in the clinics today is still limited and this is attributed to multiple challenges, including:

  • Reimbursement challenges constraining the use of liquid biopsy for early screening due to test accuracy and yielding of questionable clinically actionable information
  • Tissue is still the preferred sample type if possible when it comes to therapy selection, given liquid biopsy may not be as accurate in identifying more complex fusions and other biomarkers
  • Linking clinical outcomes to the utility of liquid biopsy in monitoring is still in its early stages

However, hospitals and AMCs can drive awareness, education, and improved testing outcomes by developing capabilities to conduct liquid biopsy testing in-house (in the form of LDTs). While RUO (research use only) kits may represent an attractive space for growth and revenue for diagnostic manufacturers, hospitals can leverage these RUO kits to improve familiarity and/or improvise their own LDTs.

At this time, diagnostic manufacturers and specialty labs are driving reimbursement initiatives, including public-private partnerships, test sponsorships, inclusion in treatment guidelines etc. but with healthcare providers taking ownership and driving more active participation in the development and refinement of liquid biopsy tests and access to these tests, the market may be able to unlock this potential more concertedly – not in the least by helping generate the RWE payers are increasingly focused on, and that help fill the data gaps that exist.

The opportunities for liquid biopsy are real, but realizing its true potential requires a focused corporate strategy for many key market players. By no means are the above activities a comprehensive list of ‘must dos’ for unlocking the value of this technology—based on decades of experience and dozens of clients, we’ve highlighted a few sample areas that major stakeholders in the liquid biopsy ecosystem can start investing in to unlock the potential that liquid biopsy holds.

To learn more about KPMG Precision Medicine Insights database, visit our website.


Special thanks to:
Puja Ghelani, Efe Alyanak, Sophie Kijel, Erik Landry, Emily McPhee, Ping Ngok