NEW YORK (GenomeWeb) – Personalized wellness firm Arivale is entering a new period of research partnerships, exploring how the multi-omic, longitudinal dataset generated by its genomics-informed health coaching business could generate new diagnostic biomarkers or inform development of future therapeutics.
The company continues to work with founder Leroy Hood and collaborators at the Institute for Systems Biology and Providence St. Joseph Health in Seattle. It has also begun a study of Alzheimer's disease with California's Hoag Health Network, another on inflammatory bowel disease with the University of Michigan, a projectin breast cancer survivors with the Swedish Cancer Institute, and an observational study examining the oral microbiome with Colgate.
Mining its data for insights into disease diagnosis and treatment has been part of the company's mandate from the beginning but now becoming formalized in a new way, fueled by data from a cohort of more than 15,000 customers, some of whom the company has now followed for up to four years.
"It was always the [goal] to be able to make a material impact not just on wellness but also on helping people identify disease early and helping physicians … intervene before a person really progressed towards these diseases that create a tremendous amount of suffering," said Mia Nease, founder of Arivale's research group and head of healthcare and life sciences partnerships for the company.
According to Nease, Arivale has reached a "critical mass" of data, both in terms of member genome sequences and longitudinal monitoring, analyzed for what the company has previously described as 'transitions': some change from health to less-health or vice versa, or in sad cases, from illness to more severe illness and even death.
"We have seen and observed these transitions … and observed things that allow us to then go to our collaborative partners who are deep subject matter experts in their [respective] disease states to say 'OK, this is what we're observed. Now how can we figure out what that means in terms of therapeutic interventions [and] lifestyle change," she added.
Andrew Magis, Arivale's director of research, argued that the company's new effort with the University of Michigan illustrates the distinctiveness and attractiveness of its dataset, compared to other longitudinal cohort data that investigators might mine.
In addition to taking multi-omic measurements in the same individuals over time, Magis said, Arivale has been able to keep very high consistency, maintaining relationships with the same vendors with "standard procedures for collection and batch correction and removing noise."
All of this, he argued, makes a big difference in the likelihood of finding a signal when analyzing the data in question. "If you try and cobble together a meta-analysis from datasets that have been collected from lots of different vendors or lots of different sources — and we find this with many things that we look at — oftentimes the noise of that batch overwhelms [the disease state] that you're studying," he explained.
With University of Michigan researchers, Arivale has been sharing data to recapitulate results the university generated in mouse models — identifying specific genes associated with a risk for inflammatory bowel disease.
"They are genes that produce reactive oxygen species that are involved in host-microbe defense in the gut," Magis said. "And since we had thousands of whole-genome sequences along with this matched patient data, we were able to look at rare variants in … the human homologues of these genes and then perform a phenome-wide association study … to look for the effects of being a carrier of one of these rare variants."
In doing so, the collaborators have already found "a number of interesting proteins and metabolites, as well as microbiome taxa," that differed between carriers and non-carriers.
"They were able to take this data back into their mouse models and validate it," Magis added. "So we have all this great validation data now showing that there is a similar effect in both mice and humans with … loss of function mutations in these genes … And we can explore 'what does this mean? How could this be used either as a diagnostic marker or as a potential therapeutic marker for IBD?'"
The company and the Michigan researchers are writing a joint paper describing the results in more detail, which they hope to publish in a peer-reviewed journal.
As much as the company's various research efforts are aligned with the discovery goals of partner institutions or companies, they also support Arivale's own interest as it pushes for recognition of its business model — health and wellness coaching informed by genomic risk data and repeat monitoring of molecular biomarkers — as clinically useful and worth its expenditure.
Some of the research studies are addressing this question directly — looking at whether (and how) the wellness interventions, dietary advice, and other suggestions that the company already offers customers, based on existing scientific understanding, actually improve their health.
For example, the Alzheimer's study with Hoag Hospital includes a randomized intervention aspect, in which Alzheimer's patients are receiving either standard-of-care or standard-of-care plus Arivale's coaching to test the hypothesis that this kind of lifestyle intervention can help slow the progression of the disease.
In the breast cancer trial with the Swedish Cancer Institute, Arivale hopes to measure the effect of its program in helping women who have been treated with chemotherapy and radiation "get back to a wellness state."
But Lewis said Arivale recognizes that the ability to prove the utility of its model may also depend on the longer-term biomarker and therapeutic discovery opportunities in these two studies and others. In other words, as the science that is being generated from its cohort potentially expands the kinds of insights and interventions that it can offer customers, the value of its service should become easier to demonstrate.
"What we see in healthcare is, all the incentives are perverse in nature, so you only get reimbursed if you're treating a condition, you don't actually get reimbursed for intercepting a condition or keeping someone well," Lewis argued. 'That is a major structural flaw in the system and it's going to take something transformational to shift."
According to Nease, it's hard to define a tipping point in this process, but there are also factors at play outside of the question of adding to the toolbox of interventions that can be made based on genetics and biomarker monitoring, and proving that those interventions are cost effective. Trends in healthcare system consolidation and outcomes-based reimbursement have also combined to incentivize preventive approaches, she said.
Alongside Arivale's efforts to advance science that can improve the utility of its wellness model, and to prove the model itself, Lewis said a key aspect will be to continue to push prices down. In that vein, the firm has reduced the costs of its services from $3,500 for a year or about $1,000 for three months in 2017 to $199 per month now.
The company also made a change to offer an option for wellness consultation without genetics and blood monitoring, but Lewis explained that that is more of a way to help interested customers engage with the company, and hopefully become slowly comfortable with the implementation of genetic and other testing, rather than an intention to actually offer long-term coaching in isolation from the scientific aspects it has made its cornerstone.
Nease added that in addition to a growing research focus, Arivale intends to expand on consumer-driven partnerships this year, focusing on ways in which it might be able to improve individuals' use of things like vitamins, probiotics, and other over-the-counter products.