LONDON – Twenty years on from sequencing of the first draft of the human genome and the associated hype, 2019 was the year that the science of genomics truly began to make an impact in health care.

From being restricted to research, genome sequencing is being applied to clinical practice, in the diagnosis of infections and monitoring of antimicrobial resistance; in rare disease diagnoses; the preimplantation and prenatal detection of inherited disorders; and the mutational profiling of tumors to guide treatment of cancer.

At the same time, wider uptake and application of genome sequencing in health care is generating huge datasets linking genes and longitudinal health records that provide an unprecedented resource for biomedical research. From being limited to looking at variants implicated in a single disease in small cohorts, it is becoming possible to investigate the genetic underpinnings of multiple disorders at once.

Clinical deployment is being enabled by regulatory approvals and reimbursement for gene-targeted therapies and genomics-based diagnostics.

Liquid biopsy tests for isolating and profiling tumor DNA from blood are a notable case in point. For example, in April, Inivata Ltd., of Research Triangle Park, N.C., secured Medicare coverage of its test for screening 36 genes that commonly are mutated in advanced non-small-cell lung cancer (NSCLC). That both avoids the need for a tissue biopsy and enables patients to get faster access to appropriate targeted therapies.

Blood samples sent to Inivata’s lab are sequenced within seven days. That compares to the two to four weeks required to extract and process a tissue biopsy. A study published in 2017 showed fewer than 10% of patients with NSCLC were profiled for all the genes for which there are FDA-approved therapies.

There is a job to do educating clinicians that liquid biopsy is here and now. But with clinical data indicating tumor DNA picks up 26% more actionable mutations than tissue profiling, coupled with the ease of doing the Inivata test, adoption will lead on to improved care.

Another example of the way in which genomic testing is translating into routine clinical care comes from Cambridge, U.K.-based Predictimmune Ltd.’s approved prognostic test for inflammatory bowel disease (IBD). The gene expression signature of 17 genes in T cells extracted from blood at the point of initial diagnosis singles out patients who are likely to have a relapsing course of disease.

That allows those patients to have first-line treatment with anti-TNF alpha drugs, rather than starting on steroids and moving on to antibody therapy following a relapse, as is the practice in Europe.

In the U.S., where it is common to begin treatment of IBD with anti-TNF therapies, it will become possible to avoid overtreatment and side effects in those patients with less aggressive disease.

In addition to informing treatment, better understanding of the likely course of IBD is allowing for earlier discussion of appropriate lifestyle changes.

As those examples show, single gene assays and targeted gene panels are demonstrating their worth in the clinic. Following on behind are regulatory-approved whole exome sequencing assays, with Nanthealth Inc., of Culver City, Calif., last month securing FDA approval of Omics Core, the first such test.

Omics Core determines the overall mutational profile of a tumor by sequencing 19,396 protein coding genes in a patient’s tumor and their healthy tissue, using circulating tumor DNA or mucosal membrane samples. That pinpoints all the acquired gene-coding mutations in a tumor genome. The information can be used to identify tumors that are susceptible to immunotherapies.

Genomics testing to pick up mutations also is being applied in infectious diseases, to track the emergence of resistance to antimicrobial drugs. For example, in November, Vela Diagnostic’s Sentosa test became the first HIV-1 genotyping assay to receive marketing authorization from the FDA.

Singapore-based Vela’s test is able to detect 342 drug resistance mutations in HIV-1. It can be used to choose the best treatments for patients who are newly diagnosed, or to switch a patient to another antiretroviral when resistance emerges.

In oncology, genome science has underpinned development of more than 50 targeted drugs aimed at 20 molecular alterations in tumors, and genomics data are beginning to make an impact on treatment decisions.

Currently, around 10% of patients could benefit from genome-targeted therapies, aimed at mutations such as Brc-Abl or ALK. Another 17% are estimated to be able to benefit from therapies, such as PARP inhibitors, which do not directly target a tumor-driven mutation, but rather the vulnerabilities that arise as a result of a mutation.

Moving toward routine care

As the here-and-now examples above demonstrate, genomics is beginning to deliver the promised dividends of the human genome project in health care. However, for now, it is being applied on a case-by-case or product-by-product basis. But based on those advances, some countries have launched plans to roll out genomic medicine at scale.

For example, France’s Plan for Genomic Medicine 2025, aims to integrate genomics into routine care, setting up 12 ultra-high-throughput sequencing labs around the country and a national data analysis hub to interpret and store data.

Another center is responsible for developing tools and processes and for implementation and workforce training.

In the U.K., it is now a year since the government-sponsored 100,000 Genomes Project reached its target of sequencing 100,000 genomes from rare diseases patients and their parents, and of cancer patients. In July, those sequences were made available for research.

Actionable findings have been uncovered in one of five rare diseases patients and half of cancer patients. With advances in genomics coming thick and fast, it is intended to look again at the sequences of rare diseases patients who did not get a diagnosis the first time around.

The project, conceived as a pathfinder for bringing genomics into routine use in the National Health Service, has now led on to the formation of the Genomic Medicine Service, with a target to sequence 5 million genomes in the U.K. within five years.

That will provide equity of access to the full range of available genomics tests, standardizing testing for all patients. For the first time, whole genome sequencing will be available as a diagnostic test for a number of specific conditions, including 21 rare diseases, all pediatric tumors and some adult cancers, including sarcoma and acute leukemias.

Building on that, in November, the U.K. government announced a pilot program in which 20,000 newborns will have their whole genomes sequenced and curated for use in their future health care.

There is still some way to go, but this can be seen as a first step to systematically applying genomics for all.

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