GeneDx pushes for faster rare disease diagnosis

It takes an average of six years for most patients to get accurately diagnosed with a rare disease after symptoms begin, according to the National Organization for Rare Diseases.

Katherine Stueland, CEO of genetic testing company GeneDx, wants to change that.

“It seems unconscionable that families are going through [a yearslong journey] when we can rule in or rule out whether or not there’s an underlying genetic diagnosis within a matter of weeks,” she told Healthcare Brew.

About 80% of rare diseases are genetic, according to the National Human Genome Research Institute. A 2023 meta-analysis suggests that genome sequencing—analyzing a person’s DNA—and exome sequencing—analyzing protein-coding genes—diagnoses those rare diseases in about 38% and 34%, respectively, of people referred for testing.

“Part of what we need to do is really take an exome and a genome off of this pedestal as a test of last resort, and educate providers and families that results are fast, they are affordable,” Stueland said.

Gathering evidence

One potential solution? Normalizing newborn testing for a large number of rare diseases.

In the ongoing Genomic Uniform-screening Against Rare Disease in All Newborns (Guardian) study, GeneDx, Columbia University Irving Medical Center, NewYork-Presbyterian, and other hospitals and researchers are testing the effectiveness of genome sequencing on top of the standard screening all newborns undergo in the US.

Results published in JAMA in October found that of the nearly 4,000 babies successfully screened between the study’s September 2022 start and July 2023, 3.7% tested positive for an early-onset genetic condition, including some treatable conditions—like a rare heart condition called long QT syndrome—that weren’t identified in the standard newborn screening.

“We’re actually delivering clinically actionable information,” Stueland said. “We’re able to, with the provider, direct the family to add zinc as a supplement, put the baby on a ketogenic diet, enroll in a clinical trial, or have access to an FDA-approved therapy.”

The initial results sequenced for 156 treatable early-onset genetic conditions, plus an optional 99 neurodevelopmental disorders. The study has since expanded to check for more than 450 conditions, she said.

In contrast, the US Department of Health and Human Services currently recommends newborns be screened for 38 core conditions and 26 optional conditions.

GeneDx’s future

Alongside its screening efforts, GeneDx became profitable in Q3 this year—the first time since it was founded in 2000—netting $1.2 million and producing 19,262 exome and genome test results for the quarter, the company announced on October 29.

The publicly traded company also announced last month that it would allow biopharmaceutical companies to analyze its deidentified genetic dataset, which has 700,000+ clinical exomes and genomes, through its data visualization tool GeneDx Discover.

This follows other initiatives like the UK Biobank Exome Sequencing Consortium, a partnership through which the publicly accessible UK Biobank database and research resource shares exome sequencing data with at least eight biopharmaceutical companies.

In a 2021 perspective article about this consortium, published in the journal Nature Genetics, researchers from Bristol Myers Squibb, Regeneron, Biogen and other major pharmaceutical companies argued that large genetic biobanks can help drugmakers pinpoint the causes of rare diseases, identify drug targets, and predict potential side effects.

Considering counterpoints

A July 2023 editorial by medical journal the Lancet’s editorial board, however, noted that genome sequencing of newborns may have several drawbacks.

The editorial doesn’t mention the Guardian study but talks about similar efforts, like the UK National Health Service-embedded Newborn Genomes Programme, which aims to sequence whole genomes of 100,000 newborns in the UK.

The authors wrote that the psychological and financial toll of genome sequencing can be significant due to potential uncertain results, follow-up appointments, and tests.

The Guardian study’s October results, 25 positive screen results were found to be false positives after additional testing, according to October’s JAMA article.

It’s also possible that genetic data in these projects could be leaked, and there’s a long-term ethical concern with parents sharing genetic information of babies who can’t consent, the Lancet authors added.

Stueland, however, emphasized in a statement that genomic newborn screening is “the key to earlier, more accurate diagnosis and treatment for rare diseases,” and that GeneDx only tests for treatable conditions.

”Guardian is not burdening parents and families with nonactionable, risk-related information,” she said.