Companion diagnostics (CDx) are developed alongside the drug using the drug diagnostic co-development model. The field has expanded from a handful of oncology drugs with corresponding diagnostics to include multiple therapeutic areas, and the number of combinations has grown significantly over the years.
Below are the top technology trends impacting the CDx theme, as identified by GlobalData.
Big data and companion diagnostics
The use of algorithms that employ big data to facilitate clinical decision-making will be more widespread in the future. These algorithms typically require large datasets with many variables such as genetic information as well as clinical characteristics including disease activity and progression. Using this information, clinicians are then able to predict prognosis and optimal treatment options using patient-level characteristics.
New information can be added to the knowledge base, regularly updating the algorithms. Aggregating data from different sources helps identify patterns that would not normally be identified if the data points were analyzed independently. Companies such as Foundation Medicine, Congenica, deCODE Genetics and Illumina use this type of approach for their products.
Artificial Intelligence (AI)
The large datasets collected continuously from various molecular profiles, in addition to the development and deployment of wearable medical devices and mobile health applications, have enabled the wide application of AI. New research opportunities in predictive diagnostics and precision medicine with the use of AI have emerged in recent years.
Many companies are also using AI in their products. Amplion, a leading precision medical intelligence company, recently launched Dx:Revenue, a software intelligence platform that uses machine learning (ML) to deliver insights to pharmaceutical partnerships. Deep Genomics, a Toronto startup, uses AI to reduce costly trial and error in drug discovery by analyzing large genomic databases. The company aims to identify patterns in large datasets of genetic information and medical records, looking for mutations and links to disease.
In cancer research and care, biomarkers used in the development of precision medicine provide a strategic opportunity for technological developments to improve human health and reduce healthcare costs. Cancer biomarkers can be categorized as predictive or prognostic based on their use. Predictive biomarkers predict response to specific therapeutic interventions such as HER2 positivity/activation, which predicts response to trastuzumab in breast cancer.
Prognostic biomarkers may not directly relate to or trigger specific treatment decisions, but rather aim to inform physicians about the risk of clinical outcomes such as cancer recurrence or disease progression in the future. Biomarker research is arguably still in its infancy, as new biomarkers are still being discovered and their clinical utility is increasingly understood.
Recently, there has been an increased use of biomarkers in clinical trials. More than 90% of oncology drugs that enter clinical development will not reach marketing authorization because clinical trials have failed to demonstrate therapeutic benefit, contributing to costly and slow cancer drug development. The role of biomarkers should therefore play an important role in minimizing the risk of failure of clinical trials.
Lab-developed tests and companion diagnostics
A laboratory-developed test (LDT) is a type of diagnostic test that is designed, performed, and used in a single laboratory. In contrast, in vitro diagnostic (IVD) tests are U.S. Food and Drug Administration (FDA)-approved diagnostic tests sold as complete kits that a laboratory purchases from a manufacturer. Many labs opt to use LDTs because they are generally much less regulated than commercial CDx. As a result, medical center laboratories have been at the forefront of precision medicine, rapidly developing tests for rare diseases, public health threats, and oncology.
In emerging markets, the high cost of imported test kits, poorly defined reimbursement processes, and an underdeveloped private health insurance sector have driven the use of LDTs. Nevertheless, some LDTs (such as those for ovarian and cervical cancers) have been associated with serious safety concerns.
Next Generation Sequencing (NSG)
Sequencing technologies have rapidly advanced in recent years, moving from traditional first-generation sequencing methods such as Sanger to more advanced second-generation sequencing such as NGS. Although highly accurate, Sanger sequencing has low sensitivity, can be complex and time consuming, and is not standardized in terms of laboratory practice. NGS enables rapid and accurate sequencing of an entire genome by both fragmenting DNA and sequencing these fragments in an automated and parallel fashion.
NGS can be used for whole genome sequencing, exome sequencing, transcriptome sequencing (RNA sequencing), and targeted sequencing of multigene panels. Genome-wide sequencing has enabled major advances in understanding the molecular bases of cancer. Doctors are able to sequence their patients’ tumors to match them with therapies designed to target the genetic alterations causing tumor growth.
Many companies are capitalizing on the need for personalized treatments by offering different NGS technologies. Illumina offers sequencing by synthesis with its Solexa system and semiconductor sequencing with its Ion Torrent system, while Thermo Fisher offers sequencing by ligation with its SOLiD/Life Technologies system.
The diagnosis and screening of tumors by non-invasive methods represents an important paradigm shift in precision medicine. Tumors are highly heterogeneous, and tumor detection methods such as tissue biopsies are invasive and do not fully reflect tumor dynamics or treatment sensitivity. One area of active research has been the evaluation of alternative sources of test material. More recently, liquid biopsies – the detection of mutations from circulating tumor DNA (ctDNA) found in the plasma of primary tumors – have gained popularity.
Obtaining enough tumor tissue for testing can be quite difficult, especially when the biopsy sample is insufficient and invasive procedures pose a health risk to patients. For example, approximately 27-31% of patients with non-small cell lung carcinoma (NSCLC) are unable to provide an appropriate specimen at diagnosis. Liquid biopsies are a minimally invasive alternative method. Additionally, ctDNA genomic analysis has the potential to offer insight into multiple metastatic sites. This is particularly useful in settings of increased genomic heterogeneity, such as in patients with treatment resistance.
There are a limited number of liquid biopsies marketed for use as companion diagnostics on the market. Companies such as Roche and Amoy diagnostics sell liquid biopsies that detect mutations in the epidermal growth factor receptor (EGFR) (NSCLC biomarker) in ctDNA, Sysmex sells liquid biopsies that detect KRAS mutations (biomarker for colorectal cancer ), while Illumina recently announced the launch of its first liquid biopsy solution for the detection of cancer biomarkers.
This is an edited excerpt from Companion Diagnosis – Thematic research report produced by GlobalData Thematic Research.