NEW YORK (GenomeWeb) – Decode Genetics and Intermountain Healthcare are aiming to amass the biggest research repository of genomic and patient outcomes data by sequencing the genomes of 500,000 individuals.
Through the population health initiative, called HerediGene, Intermountain aims to improve understanding of the underlying causes of disease and use that information to take better care of its patients. Icelandic firm Decode hopes to also unravel the complexity of human disease, and will put that knowledge toward discovering and validating drug targets, something it has already been doing for more than half a decade for its parent firm Amgen.
"We'll be aggregating maybe the largest ever combined genomics and clinical outcomes database over the next five years," said Lincoln Nadauld, Intermountain's chief of precision health. "Intermountain's goal is to turn around and use those insights to change the way that we manage patients so that we can intervene earlier, so we can screen patients and do surveillance in a way that allows us to prevent certain conditions or health events from happening."
The half-a-million HerediGene participants, meanwhile, will have the chance to learn if they harbor clinically actionable, disease-linked variants in 59 genes that the American College of Medical Genetics and Genomics has said should be reported to patients. Anyone over the age of 18 living in the communities served by Intermountain in Utah and Idaho will be eligible to partake in the initiative. "We're actually approaching this in a non-discriminatory fashion and we will be collecting samples from all comers," including healthy and sick people, said Nadauld.
Intermountain will consent patients into the study, collect samples for analysis, and send them, anonymized, to Decode in Iceland for analysis. Decode will conduct the genomic analysis on de-identified samples, but both partners will have access to the research data.
"Our role in this is to simply discover what it is that characterizes a group of people who share a disease or share a response to treatment," said Decode Genetics CEO Kári Stefánsson, emphasizing that the company will not have access to identifiable information on Intermountain patients. "We have no interest in data on individuals."
Genome sequencing conducted within the HerediGene initiative will be free for participants and the costs will be borne by the collaborators. While Nadauld wouldn't disclose how much money the health system is committing to the project, he noted that both Intermountain and Decode are "investing heavily." As such, they will have access to the data and opportunities to advance new technologies and interventions based on the findings.
"This initiative is one of our top priorities because of the scale of investment," Nadauld said. "I think it represents how serious we are about precision health … If there is a novel technology, if there is a cutting-edge approach, including mapping genomes, that will better help our patients, we'll invest as needed to make that a reality for our patients."
The collaboration fits with Intermountain's increasing interest in using genomics in patient care. Intermountain has tried to improve patient health by decreasing variation in care delivery, and by focusing on patient safety. But more recently, the health system has been investing in precision health approaches.
In oncology, for example, Intermountain was an early adopter of genomics in 2013, when it decided to offer all stage IV cancer patients tumor profiling on a large panel of cancer-linked genes and use the results to inform treatment. More recently, Intermountain rolled out a 104-gene panel for germline testing to assess the hereditary risks for cancer patients and their families. This test is offered to all newly diagnosed cancer patients.
In deciding to report back actionable variants in the ACMG-59 genes, Intermountain estimates that 3 percent of participants will receive results. As a result, Intermountain had to set up the infrastructure to ensure that patients were receiving accurate results and had the necessary support to integrate the information in their care.
A clinically actionable finding via whole-genome sequencing by Decode will have to be reanalyzed and confirmed by Intermountain in its CLIA lab. In-house genetic counselors will then reach out to individuals with positive results to guide them about screenings, additional follow-up interventions, and cascade testing for family members.
In partnering with Intermountain, Stefánsson was intrigued that the Utah health system's goals appeared to align with the Scandanavian healthcare model of "not just trying to deal with disease, but also to help its population to maintain health."
Since its launch in 1996, Decode has amassed extensive experience with population genomics within its home country and elsewhere. For example, Decode has performed extensive DNA sequencing for the National University Hospital of Iceland and there, Stefánsson believes his company has had the most direct impact on healthcare by helping the hospital diagnose rare genetic childhood disorders.
Before Amgen acquired it in 2012, the company had tried its hand at drug and diagnostic development, launched a consumer genomics arm, and survived bankruptcy. All the while, the company maintained its focus on building repositories of genomic and clinical data, largely on the Icelandic population, and these data have been the engine for its novel gene-disease discoveries.
Decode has genotypic and medical data on 175,000 Icelanders, a genealogy database that spans nearly all of Iceland's current population of around 300,000 people, and phenotypic data stored in an electronic medical record system. The firm also has whole-genome sequencing data on about 80,000 Icelanders. The WGS and outcomes data on an additional 500,000 individuals from the Intermountain collaboration will make it the largest repository of its kind, Stefánsson said.
Greater access to genomic and clinical data from more diverse populations will increase the pace of discoveries, he firmly believes. "We've made a lot of discoveries, but there is an awful lot about the nature of disease that is yet to be discovered," Stefánsson said. "What you're doing is trying to understand human diversity when it comes to disease."
Amgen, too, is hopeful that the data collected within this collaboration will aid its drug discovery and development efforts. A spokesperson for the company said that bringing Decode under its aegis more than six years ago has already "fundamentally changed the composition of Amgen's pipeline."
Before acquiring Decode in 2012, about 16 percent of drugs in Amgen's pipeline were genetically validated, but since then, this has risen to more than 75 percent. The conventional wisdom is that genetically validated targets provide more certainty about the chances that drugs interrogating those targets will reach patients, and ideally, get to market faster and cost effectively.
Amgen has held up Decode's discovery of a rare mutation in ASGR1 and its association with a 34 percent lower risk of coronary artery disease as an example of how genomics is informing its drug development work. The company announced a few years ago that it would take this genomic insight and develop a treatment for heart disease. Researchers from Amgen even published Phase I safety data on AMG 529, an anti-ASGR1 monoclonal antibody.
Although Amgen has since decided to stop advancing AMG 529, because it didn't meet its "strict commercialization criteria," the drugmaker hasn't yet given up on trying to target ASGR1 with other modalities. An Amgen spokesperson said that the firm is still working on understanding the mechanism linking ASGR1 to heart disease and has been pursuing other strategies to interrogate the target. "We remain enthusiastic about ASGR1 as a target based on the genetic data," the spokesperson said.
Amgen isn't the only company trying to de-risk its pipeline with large-scale genomic data. The type of population health research model Intermountain and Decode are embarking on has been successfully executed by Regeneron Pharmaceuticals and Geisinger Health in Pennsylvania through a collaboration inked in 2014.
Within Geisinger's MyCode Community Health Initiative, consenting patients have their exomes sequenced by Regeneron and around 2 percent of participants receive results indicating they have a likely pathogenic or pathogenic variants in 76 genes associated with 27 conditions. By next month, Regeneron will have sequenced the exomes of 145,000 MyCode participants, and more than 1,000 patients have received results so far.
AstraZeneca announced in 2016 that it would partner with Human Longevity, the Wellcome Trust Sanger Institute, and the Institute for Molecular Medicine in Finland, to analyze the genomes of 2 million patients to bolster its drug discovery engine.
And GlaxoSmithKline inked a four-year exclusive pact with consumer genomics firm 23andMe last year to gain access to genomic and clinical data on consenting customers. Although, the majority of 23andMe's customers agree to contribute their data research, the deal did raise concerns among industry observers and bioethicists as to whether consumers truly understood what they were consenting to.
In a website explaining the HerediGene initiative to potential participants, Intermountain is careful to explain that this effort to whole-genome sequence 500,000 people is quite different from the genotyping done by popular consumer genomics firms, such as 23andMe and Ancestry.com. Additionally, unlike the consumer genomics research model, Intermountain's patients will not pay to be whole-genome sequenced, and can still receive results back if they wish.
Early feedback, according to Nadauld, suggests that people perceive the collaboration with Decode as a positive opportunity for the regions Intermountain serves. "There is enthusiasm … when they understand that a major healthcare provider in the community is investing heavily to prevent disease, and help them and their families live the healthiest lives possible," Nadauld said.