This article has been updated to include a comment from a Helix customer and to correct that it is whole-exome sequencing, not Helix's Exome+ assay, that was authorized by the FDA.
NEW YORK – Helix said on Monday that it has received de novo authorization from the US Food and Drug Administration for its whole-exome sequencing platform, as well as 510(k) clearance for a direct-to-consumer genetic risk test for late-onset Alzheimer's disease.
The Helix Laboratory Platform is the first whole-exome sequencing platform to be authorized by the agency. It was analytically validated using a novel representative sampling-based approach together with defined quality metrics to establish its accuracy and reproducibility.
The clearance of the Alzheimer's test, called Helix Genetic Health Risk App (HRA) for late-onset Alzheimer's disease, serves as a template for additional germline tests the company and its partners plan to seek market authorization for, including for cancer, cardiovascular disease, and carrier screening.
"We are excited to have pioneered this new regulatory authorization pathway to help health systems, life sciences companies, and payors to accelerate the advancement of genomic discoveries from bench to bedside," said Helix CEO Marc Stapley in a statement.
The Helix Laboratory Platform is authorized as a qualitative in vitro diagnostic device for exome sequencing and the detection of single nucleotide variants and small insertions and deletions in human genomic DNA extracted from saliva samples collected with the Oragene Dx OGD-610 kit. It is intended for use with specific germline assays authorized by the FDA and runs in Helix's CLIA/CAP laboratory in San Diego.
The Alzheimer's test determines the e2/e2, e2/e3, e3/e3, e2/e4, e3/e4, and e4/e4 genotypes in the APOE gene and reports whether a result is associated with an increased or decreased risk of developing late-onset Alzheimer's disease.
James Lu, president and cofounder of Helix, said in an interview that the structure of the authorization — separating the assay platform from the tests — fits well with the company's model to 'sequence once, query often.' "We want to generate a really high-quality dataset and be able to use that over and over again," he said. "So there is a decoupling of the data generation and the data usage components, which we always thought was essential in genomics, but historically, it has really never been that."
The representative sampling approach for the validation, he explained, involved building a series of quality metrics to infer the sequencing accuracy at different genomic positions, and then validating those quality metrics across thousands of clinical samples.
The quality metrics included sequencing coverage, for example, but also involved removing, or blacklisting, regions in the genome that are known to be difficult to sequence. "We used quality metrics as the way to ascertain the underlying accuracy of a data point," he said. "That does give us a broad swath of genome that falls within this category of representative sampling."
However, certain variant types — in particular, general copy number variants — are not covered yet under the current authorization, though they may become important over time. Helix will be adding content, "both from an applications perspective but also from a technical performance perspective, over time," Lu said.
While the current authorization is for exome sequencing only — and not Helix's Exome+ assay, which includes a clinical exome and about 300,000 informative noncoding regions, as well as the mitochondrial genome — the same validation approach could be used for even broader assays in the future, he said, including whole-genome sequencing. For now, and until the price of whole-genome sequencing comes further down, Helix will stick with an exome-based assay, though.
The Alzheimer's disease risk test, which relies on the exome data, serves as template for other virtual panels. "We view this first reference application, APOE, as a starting point," Lu said. "Additional applications and panels of tests require very little additional laboratory validation because we have validated the platform."
Also, the fact that the Alzheimer's test and, presumably, future tests, is authorized for over-the-counter (or direct-to-consumer) use, provides additional flexibility that can be helpful, even though Helix's main business is population genomics rather than DTC services. "Sometimes it may be easier to enable a direct-to-consumer workflow that has proper follow-up with a provider," Lu said.
The authorization process took more than a year, he said, and the FDA has been "incredibly collaborative throughout the process in making sure that we can get to the right place."
Having an FDA-authorized platform and test "provides us with new market opportunities and the ability to offer patients a higher-quality product," he said. In particular, the firm believes it will help in discussion with health systems, payors, and life science companies.
Population genomics projects, in collaboration with health systems, remain Helix's core business, he said. Three large ongoing projects — with the Renown Institute for Health Innovation, AdventHealth Orlando, and the Mayo Clinic — have all restarted their recruitment during the COVID-19 pandemic, he said, and some projects have switched to digital enrollment and at-home sample collection.
"This is an important recognition by the FDA of the necessity of clinical whole-exome sequencing in genetic risk assessment and an acknowledgement of the sequencing platform and its output as a clinical product," said Joseph Grzymski, CSO of Renown Health, in an email. "The Healthy Nevada Project and Renown Health are excited about our longstanding partnership with Helix as we expand benefits to our participants and patient population on the only FDA-authorized platform."