Page 24 adjusted appropriately . This also brings economic benefits in the form of lower costs for clinical trials and less inappropriate use of expensive drugs .
Development of minimally invasive liquid biopsies facilitates the development of rapid multiparameter disease profiling and monitoring
The discovery and use of relevant diagnostic biomarkers are driven by the increasing ability to rapidly detect and analyse low levels of DNA and other biomolecules through rapid progress in technologies including next generation sequencing . These innovations will drive the development of liquid biopsies ( mostly from blood ), measuring multiple molecular parameters without the need to frequently access scarce tissue . The ability to measure multiple parameters from blood enables the development of diagnostic panels that combine companion and complementary diagnostic tests with the prognostic tests that guide the broader therapeutic approach to further personalise patient care . Developments in immunotherapy and the understanding of the role of immunity in cancer progression will drive an increasing need for biomarkers capable of predicting and guiding the response to checkpoint inhibitors and a whole new range of other immunotherapies and their combinations .
Substantial scientific , technical , and other challenges
The scientific and technical challenges of identifying relevant biomarkers and developing companion and related diagnostics remain substantial , as summarised below ( Figure 19 ).
Figure 19 : Challenges to the adoption of CDx
• Lack of standardisation for a test can limit use outside of centres with high levels of oncology expertise
Clinical
• Depending on indication , there may be limited treatment options , making it difficult to exclude patients based on biomarker expression
Economic
Scientific
Other
• Biomarkers can reduce patient population size , thus limiting the market opportunity for cancer drugs
• The majority if ICI to date have been approved on their own in the absence of a biomarker
• Regulatory agencies are still unfamiliar with liquid biopsies and criteria for market clearance may yet still evolve
• PD-L1 diagnostics have proven unreliable due to the dynamic expression of this biomarker
• Requirements to combine biomarkers adds complexity
Source : goetzpartners Research
Ensuring accuracy of CDx tests can be difficult and different for the same marker in separate cancers
CDx biomarkers are difficult to predict accuracy Many of the targets only occur in a very small proportion of patients ( sometimes < 5 %). Some patients test positive for more than one driver mutation , meaning that physicians must base their choice on additional factors . Although the advent of NGS technologies has facilitated biomarker identification and analysis , the validation of the clinical utility of such markers will remain a challenge , due to the inherent heterogeneity of cancer . Pembrolizumab is FDA approved for different biomarkers including microsatellite instability (“ MSI ”) and tumour mutational burden (“ TMB ”) as well as for PD-1 expression levels for different malignancies . While an oncology drug may have a test to predict efficacy in one cancer , this does not translate to efficacy in all cancers . This is the case with pembrolizumab and metastatic melanoma , however Novigenix are developing a liquid biopsy-based test to predict ICI effectiveness in this pathology .
Economic hurdles to diagnostic development remain The economic hurdles facing CDx development remain significant . CDx are frequently developed through collaboration between pharma and diagnostics companies . While pharmaceutical companies are increasingly bearing the cost of CDx development , the relative market value of the drug compared to the diagnostic means that the upside remains in drug development . There is little incentive for drug companies to fund the development of clinically valuable broader complementary diagnostic tests that may promote the use of drugs from other companies in the same class . Instead , they are motivated to focus on CDx that promote the use of their drugs alone .
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