2019: A Watershed Year for Genomics in Clinical Care

For her whole life, Victoria Gray has lived with the debilitating pain of sickle cell disease, a genetic condition that affects millions worldwide. She’s endured transfusions and hospitals stays, and lived with the fear that deadly complications of the disease could leave her children motherless. In July, she was the first patient in the U.S. to be treated using CRISPR-modified cells. While it’s too early to know if she’s cured, early results show that the edited cells are producing the crucial protein she needs.

2019 may well be remembered as the start of a new era of treatment for patients with genetic disease. And Victoria’s story is just one of many from 2019 showing the power and promise of genomics to improve human health. Below I have selected a few highlights from this year.

Faster, more precise diagnosis across clinical indications

Streamlined, automated diagnosis for children with genetic disease

Investigators at the Rady Children's Institute for Genomic Medicine developed a new whole-genome sequencing and interpretation pipeline for the diagnosis of rare diseases. In an average of about 20 hours this new protocol was able to provide diagnoses to critically ill infants in the NICU. By enabling faster and more widespread implementation of genomic diagnosis, this new pipeline could have an enormous impact on outcomes: an estimated 10-12% of infants admitted to regional NICUs may benefit from same-day diagnosis and implementation of targeted treatments. 

Early cancer detection in a blood sample closer than ever before

In October, Grail presented data showing that their multi-cancer early detection blood test detected cancer across all stages with a single, very low false positive rate. For the 12 most deadly cancer types, the overall detection rate was 76%. The test also identified the tissue of origin for the cancers with high accuracy, a feature that could provide doctors with critical information for diagnostic work-up and next steps. Although this test is still in development, it is enormously exciting to be on the brink of having a reliable liquid biopsy test to screen for and detect multiple cancer types. Survival rates are 5-to-10 times higher in patients whose cancers are diagnosed at early stages.

Refining risk for genomic conditions using polygenic scores

In a preprint posted in November, researchers described an analysis of more than 80,000 individuals showing that for three important genomic conditions polygenic background powerfully modifies the risk conferred by mutations in single genes. For example, the probability of breast cancer by age 75 can vary from 13% to 76% for BRCA1/2 mutation carriers based on the combination of multiple other genetic variants. These findings have important implications for understanding disease physiology and for how patients and their providers take action – whether they take preventative medication, undergo enhanced screening, or go so far as to have prophylactic surgery.  

Clinical genomic testing becoming accessible to the masses

Bringing genomics to where the patients are

Decentralization of testing through in vitro diagnostic (IVD) solutions that bring testing to where patients are being treated is critical to the continued expansion of genomics. This is especially important in cancer, where 80% of oncology practices are community treatment centers. This year we have partnered with multiple companies to enable development of IVD tests and companion diagnostics on Illumina Dx instruments. We’ve announced partnerships with Adaptive Biotechnologies, Qiagen, Lexent Bio and ArcherDx to develop IVD kits for a variety of oncology applications in the U.S. and around the world.

Health systems and payers embracing genomic testing

In 2019, England continued its preparations to become the first country to deliver whole genome sequencing to patients at scale through its Genomic Medicine Service. Tens of thousands of patients in the National Health Service will be impacted. Globally there are population genomics projects in multiple countries underway that have been inspired by England’s example of genomics on a national scale. Many of these may eventually include clinical aspects as well. 

Several large health systems and employers in the U.S. have also embraced large scale genomic testing in 2019. Ochsner Health System in New Orleans launched a digital population health screening program that is identifying patients particularly vulnerable to hereditary cancers and heart disease and recommending genomic testing. Chicago’s Northshore University HealthSystem began offering genomic health tests to more than 10,000 patients as a primary-care service – not just to patients with genetic health risks. Apple is now offering employees free genomic testing at its on-site health clinics.

Decades of research paying off: treatments and possibly cures

Medicines for “n-of-1”

Dr. Timothy Yu and his colleagues at Boston Children’s Hospital reported the creation of what’s believed to be the first “custom” treatment for a genetic disease. The drug, an antisense oligonucleotide designed to block the effects of an extraneous bit of DNA in the MFSD8 gene, is named “milasen” in honor of the only patient who will ever take it: a girl with Batten disease named Mila Makovec. She received her first dose in January 2018 and within a month her mother noticed an improvement in her symptoms. Though Mila remains severely disabled, her experience with custom genomic therapy is giving hope to other families of children with genetic disease. Lydia Seth’s parents have established the Lydian Accelerator to help accelerate this type of treatment for her and others with genetic disease. Important questions about regulation of this approach remain, however.

Gene therapies re-emerge after two-decade hiatus

After the death of Jesse Gelsinger in 1999, research on gene therapy was paused due to safety concerns, but in the intervening years there have been advances in tools and approaches. The FDA now predicts they will be approving 10 to 20 cell and gene therapy products a year by 2025.

“Bubble boy” disease

In April, encouraging results were reported in the search for a gene therapy treatment for children with X-linked severe combined immunodeficiency (SCID-X1), known colloquially as “bubble boy disease.” Previously the best available treatment was a bone marrow transplant, but only about 20% of patients were eligible. Commenting on the recent results, James Downing, president of St. Jude Children’s said “From a physiological point of view and from a quality-of-life point of view, this is a cure.” It remains to be seen whether the effects will last, but this was a momentous advancement and important change in the prospects for children who would otherwise endure a lifetime of isolation to avoid deadly infection.

Spinal muscular atrophy (SMA)

The first gene therapy for SMA, the leading genetic cause of infant mortality was approved by FDA in May. This is only the second therapy available for this devastating disease. Like the new experimental treatment for SCID-X1, Zolgensma uses a viral vector to deliver a functional copy of a gene. A one-time infusion is potentially curative, a fact that its manufacturer and patients have pointed out to critics of its high price.

Gene editing

Multiple trials are underway taking advantage of gene editing (using CRISPR and other tools) for gene therapy. In addition to the sickle cell disease trial that Victoria Gray is participating in (see beginning of this post), there are trials ongoing for beta thalassemia, MPSI and MPSII and hemophilia. In a big move forward, the first trial to deliver a CRISPR-based editing tool directly into the body is underway, aimed at correcting a mutation for an inherited type of blindness called Leber congenital amaurosis.

Looking forward to 2020

In spite of these breakthroughs, there is still so much more to learn. Less than 0.02% of humans have had their genomes sequenced, and we haven’t yet deciphered the function of 99% of the variants discovered in the human genome. Big science and data sharing initiatives are laying the groundwork for continued discovery and deeper understanding of the genome’s role in health and disease. And while reimbursement and use of genomic medicine has increased significantly, there are still too many patients for whom genomic medicine is inaccessible.

About a month after Victoria Gray left the hospital in Nashville where she received the experimental CRISPR-based treatment – what she dubbed her “supercells” – she was back for a check-up. She reported that she hadn’t had any painful sickle cell crises, she hadn’t needed to go to the hospital, and she was able to reduce her pain medication. In her view, the treatment was a miracle. "When you pray for something for so long, all you can have is hope," she said.

That’s what genomics is: hope. Hope came to many in 2019 thanks to genomics, and I feel confident that in 2020 even more patients and families will be impacted. At Illumina we’ll be entering the new year more passionate than ever to bring to life the innovations that are going to enable fundamental genomic insights into our health and the world around us.