Next-generation sequencing (NGS) in diagnostics is rapidly growing, having made great strides since the conclusion of the Human Genome Project fifteen years ago. Increasingly rapid and effective testing capabilities for hereditary diseases, cancers, cardiac and respiratory conditions, neurodegenerative disorders, and even infectious disease, are either on the horizon or have arrived. The promise of DNA sequencing through this methodology alone has attracted many companies, researchers, and investors.The Worldwide Market forIn VitroDiagnostics, 11th Edition, has been released recently, and features a significant section on molecular diagnostics, including NGS. Below is a selection of developments that have arisen in the period since our report’s August publication.
In July, Genepath Laboratories (Chatswood, NSW, Australia) launched their NextGen test, a genetic screening test for use in detecting multiple treatable conditions, in conjunction with the heel-prick newborn screening test. NextGen can screen for over 60 serious medical conditions—50 of which were not previously tested in Australia—including conditions associated with sudden infant death syndrome (SIDS), life threatening conditions like tyrosinemia and familial hemophagocytic lymphohistiocytosis, conditions that cause developmental disabilities in both physical growth and intellect, conditions leading to heart and lung diseases, and rare cancers. Sample collection for the NGS panel is a simple mouth swab that can be performed on patients of any age, but is best for newborns as the targeted conditions usually appear in the first year of life. Among the conditions tested is familial hypercholesterolemia, a condition—easily treated through diet and medication—that significantly increases risk for myocardial infarction in young adults, and is estimated to be severely underdiagnosed in Australia.
Women’s health company NxGen MDx (Grand Rapids, MI) also announced in July that they had developed a new method of DNA tagging, called active molecular identification (AMI), to track samples and prevent laboratory errors, using synthetic DNA to tag a patient’s sample at the beginning of the testing process. AMI tagging accompanies and identifies the patient’s sample throughout the entire process, and connects it to the final test results, reducing the incidence of sample mixups. Validation studies were conducted to ensure that the synthetic DNA used in the methodology does not affect testing.
Meanwhile, it was announced in August that a five-year NIH grant valued at over $8 million had been awarded for research on the clinical and economic benefits of conducting NGS testing in newborns at multiple institutions, including Cincinnati Children’s Hospital, Mt. Sinai Hospital, Rady Institute for Genomic Medicine, Tufts Medical Center, University of North Carolina-Chapel Hill, and the University of Pittsburgh. Four hundred newborns known to be at high-risk for genetic diseases, but have not yet been diagnosed, will be enrolled in the study and will receive whole-genome and targeted genomic sequencing to test for over 1,700 genetic disorders. The multiplex panel is under development with Quest Diagnostics. Results will be compared with more conventional diagnostic procedures, with focus on time to diagnosis, time to treatment, and the total costs associated with each methodology.
An article to be published in theJournal of Global Antimicrobial Resistance (DOI:10.1016/j.jgar.2018.08.018; available online, currently in press), illustrates the potential of whole-genome sequencing in more rapid and comprehensive diagnosis of drug resistant tuberculosis. A study conducted in Indonesia, which has the world’s second highest TB burden, involved the use of WGS on over 300 samples from HIV-negative TB patients, among which, nearly 16% were found to have drug-resistant strains of the disease. The concurrence rate between WGS-based testing and more conventional phenotypic drug susceptibility testing was high for rifampicin and isoniazid, but less so for streptomycin and ethambutol. A potential advantage of WGS-based testing is that testing by more conventional means has been shown to be poorly corresponded with reported prior treatment for TB, due to clinicians targeting only patients with previous treatment or other risk factors, resulting in many undetected drug-resistant cases. WGS-based testing is potentially helpful in limiting the spread of drug resistant TB by testing patients who lack such risk factors.
In August, Novogene Bioinformatics Technology (Beijing) announced approval for its NovoFocus NSCLC CDx assay by the China Food and Drug Administration. The NGS-based diagnostic analyzes tumor samples for multiple genomic mutations associated with non-small cell lung cancer, which accounts for approximately 80% of all lung cancer cases in China. Results from sequencing and analysis of ROS1, EGFR, and ALK can be used to identify NSCLC patients eligible for treatment with CFDA-approved cancer therapies including Crizotinib (XALKORI), Gefitinib (IRESSA), and Osimertinib (TAGRISSO), respectively. Other genes targeted in the panel are KRAS, BRAF, and PIK3CA. NovoFocus NSCLC CDx was developed on the Thermo Fisher Ion Proton sequencing platform.
Asuragen (Austin, TX) announced in September the expansion of its own oncology portfolio with the launch of their newly CE-markedQuantideX NGS DNA Hotspot 21 Kit. The kit is a next-generation sequencing panel designed to detect numerous tumor types, including those in colorectal cancer, melanoma, and non-small cell lung cancer. QuantideX NGS DNA Hotspot 21 uses Asuragen’s NGS-in-a-Box design and the company’s Sample-Aware bioinformatics software, which determines whether a sample has sufficient DNA that can be amplified. The panel is indicated for use on Illumina’s MiSeq platform.
IDbyDNA (San Francisco) signed a licensing agreement mid-September with Fleury Group (São Paulo, Brazil) to offer the company’sExplify platform for clinical metagenomic testing in South America, with Fleury integrating the platform into its own laboratory operations. Fleury will also develop a full suite of clinical tests for Explify, beginning with a respiratory panel that detects over 200 common, rare, and novel bacterial, viral, and fungal pathogens in respiratory specimens.
IDbyDNA, which developed Explify in collaboration with ARUP Laboratories (Salt Lake City), is in another partnership, begun in January with Locus Biosciences (Morrisville, NC), to develop a diagnostic test for the Explify platform to detect Pseudomonas æruginosa. Locus will use the test to recruit and select patients for its clinical trial for LBx-PA01, a CRISPR-based antimicrobial product that targets the pathogen, which is associated with sepsis and a number of nosocomial infections.
Jerusalem-based NovellusDx will merge with a newly-formed Israeli subsidiary of Cancer Genomics (Rutherford, NJ), which will combine the former’s expansive cancer test portfolio and large tumor biology dataset with the latter’s proprietary NGS and machine learning tech. Cancer Genomics will be the surviving entity, but NovellusDx shareholders will gain a 49% stake in the company as part of the merger agreement.
Miami-based Igenomix has developed the Analysis of Infectious Chronic Endometritis (ALICE), an NGS-based diagnostic for the uterine infection that can lead to infertility in women. As traditional diagnostic methods do not accurately identify the bacteria in endometritis, nonspecific antibiotics are often prescribed and will not always be as effective as the infection requires. ALICE requires just a small endometrial sample from which DNA is extracted; the sample undergoes bacterial analysis through next-generation sequencing. With ALICE, clinicians can detect the correct culprit and prescribe the right pro- and antibiotic to treat the infection, and improve women’s reproductive success.
Again, for the latest market analysis of next-generation sequencing-based IVD, see the eleventh edition of our flagship report,The Worldwide Market forIn VitroDiagnostics, published in August.