Oncology
specific genes, but requires yet another assay, MethylSeq.
It is possible to design a repertoire of tests aimed at different patient groups, and in the future, these could potentially be used as a screening tool for the non-symptomatic or people with early-stage symptoms. For instance, greater sensitivity tests involving broad genetic coverage and multiple technologies could be used to reveal individuals in need of further care or treatment, providing details of therapy requirements. However, for lowest-price regular assessment of groups at high risk due to familial or lifestyle factors a small-scale minimum coverage DNA sequencing test would be more appropriate. This could be used regularly to highlight the emergence of common mutations, with potentially massive savings in long-term healthcare costs as well as quality of life improvements. Nevertheless, while cfDNA tests hold much
potential to improve and accelerate cancer diagnosis and treatment, it’s important to be aware of their limitations. The risk of false positives is a critical factor that needs to be carefully considered. Scenarios where this might be an issue include recurrence surveillance when an old, dying tumour hasn’t yet been fully cleared. It can also be caused by sequencing errors which randomly arise in high-sensitivity tests, particularly after DNA amplification. Whatever the cause, the potential patient distress and associated costs require mitigation planning.
A growing opportunity We’re at an exciting juncture for liquid biopsy genetic testing, where the science, technology, and regulatory environments are broadly aligned. It’s still early days, however, and the technology requires further development and refinement. Costs need to decrease significantly to drive
the levels of engagement needed for better rates of early cancer diagnosis. The pan-cancer solutions from FoundationOne and Guardant 360 have broken new ground from a technology and regulatory perspective but currently cost £4250+ per test. Since the cost of DNA sequencing is continually reducing, with clinical-grade full- genome coverage available to consumers for as little as £255, there is huge scope for price reductions to make DNA testing more accessible and entice a broad audience to include DNA tests in regular health check-ups. For example, BUPA is already offering a wide gene panel for general health and fitness in the UK for £149 including follow-up consultation. For comparison, in the US, a cervical HPV test regularly used for screening costs less than £42,
excluding physician and collection costs. There are also many opportunities to improve
the coverage, sensitivity, and speed of liquid biopsy genetic test devices. This is an area where a lot of activity is expected over the coming months and years. While liquid biopsy testing is currently used for treatment decisions and post surveillance, it is moving into diagnosis where symptoms are present; later it will move into screening. Innovation in this space requires a pragmatic
and strategic approach, since not all cancer types release enough ctDNA for NGS analysis to be effective at standard sequencing depth. Grabbing these opportunities is key to securing or maintaining a leading position in the precision medicine market. Doing this requires substantial knowledge of how genetic variants and mutations impact human health, how they interact with each other to modify their effects, and which are directly actionable. Naturally, it’s important to understand the
growing competition to seek novel targets and market niches. However, a clear understanding of how to use morbidity statistics and population variant frequencies is also essential to ensure a sustainable product is developed with clear revenue expectations. Beyond initial product design, a growth plan is important to ensure products aren’t overtaken by a rapidly moving market. This might be achieved by increasing the genetic range, or by applying similar techniques to a growing range of medical and lifestyle situations. While there are many challenges to overcome, the regulatory situation is encouraging. Companies that pay mind to the recent FDA
approvals and develop regulatory strategies in tandem with product development strategies that empower customers and patients will be best placed to accelerate time to market. Those that make it could play a lead role at the forefront of molecular diagnostics for precision oncology and beyond, enabling many people to live longer and have better lives after cancer. CSJ
References 1 FDA, Approved Drugs, cobas EGFR Mutation Test v2
https://www.fda.gov/drugs/resources- information-approved-drugs/cobas-egfr- mutation-test-v2
2 FDA Report, Adaptive Biotechnologies ClonoSEQ Assay
https://fda.report/PMN/K200009
3 FDA, Recently Approved Devices, Guardant360 CDx – P200010
https://www.fda.gov/ medical-devices/recently-approved-devices/ guardant360-cdx-p200010
4 FDA, Recently Approved Devices, FoundationOne Liquid CDx – P190032
https://www.fda.gov/ medical-devices/recently-approved-devices/
74
www.clinicalservicesjournal.com I September 2023 About the author
Simon Forbes PhD is the head of genomics and bioinformatics at Sagentia Innovation. With 30 years’ experience in human genomics and bioinformatics, Simon was previously director of the cancer genetics project ‘COSMIC’ at the Sanger Institute. He now helps Sagentia Innovation’s clients navigate the genetic technology landscape in healthcare and beyond.
foundationone-liquid-cdx-p190032
5 FDA, Approved Drugs, FDA approves liquid biopsy NGS companion diagnostic test for multiple cancers and biomarkers https://
www.fda.gov/drugs/resources-information- approved-drugs/fda-approves-liquid-biopsy- ngs-companion-diagnostic-test-multiple- cancers-and-biomarkers
About the author
Laurie Clarke is VP and principal of medical device regulatory at Sagentia Innovation’s sister company TSG Consulting. Previously a Food and Drug Administration (FDA) partner at several large law firms she has a wealth of experience obtaining premarket authorisation for medical devices via the 510(k), PMA, de novo, and HUD/HDE pathways.
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