NEW YORK – Proteomics firm SomaLogic has developed a 27-protein panel the company believes could serve as a "universal" measure of cardiovascular risk.
Detailed in a study published last week in Science Translational Medicine, the panel provided strong discrimination between patients at the lowest and highest risk for cardiovascular events and could prove useful both in drug development work and as a clinical tool, said Stephen Williams, SomaLogic's chief medical officer and first author on the paper.
The study also offers a concrete demonstration of the depth and throughput enabled by the company's SomaScan platform. To develop their panel, SomaLogic researchers and their collaborators measured roughly 5,000 proteins in 32,130 plasma samples taken from 22,849 individuals. They then validated their results in an additional 11,609. Altogether, this makes for one of the largest — if not the largest — scale protein biomarker discovery and validation experiments done to date.
The samples came from participants in nine clinical trials covering a variety of cardiovascular risk factors and interventions, allowing the researchers to assess the performance of their markers across a wide range of conditions and treatments. They found that patients placed in the highest quintile of risk by the 27-protein panel had a 6.7-times higher rate of cardiovascular events within four years than patients in the lowest quintile of risk. That compared to a 2.9-times rate when stratifying patients based on traditional clinical measures.
The protein panel also showed the ability to detect an increase or decrease in cardiovascular risk in response to either the addition of a risk factor, such as chemotherapy treatment, or of a treatment, such as diabetes medication.
Boulder, Colorado-based SomaLogic ultimately aims to demonstrate the markers' utility for assessing risk and changes in risk in response to the full range of interventions used to treat cardiovascular conditions, though Williams noted that the company still needed to collect data on a few drug classes.
Williams indicated that SomaLogic was interested in taking the panel through the US Food and Drug Administration so that it could be used as a surrogate endpoint in clinical trials. He noted that the FDA has two regulatory pathways for surrogate endpoints — validated endpoints, which typically require extensive evidence from clinical trials before the agency will accept their use, and a less rigorous pathway in which endpoints must, in the agency's phrasing, be "reasonably likely to predict a clinical benefit."
Williams did not say which approach SomaLogic would pursue, noting that both were currently on the table.
The validated route "is a big lift, but that doesn't mean we're not prepared to do it," he said.
He noted that the STM study had been designed to align with the FDA's guidance on the qualification of surrogate endpoints.
"That doesn't guarantee that it is going to meet the requirements, but I think it raises the chances," he said.
Peter Ganz, senior author on the study and director of the Center of Excellence in Vascular Research at the Zuckerberg San Francisco General Hospital, said that another point in the panel's favor is that many of the proteins on it have causal relationships to cardiovascular phenotypes. According to the study, all 27 are linked to biological processes associated with cardiovascular risk, and 12 have "at least one genetic causal association with cardiovascular disease."
The FDA has in the past "said they would have greater confidence in [surrogate markers] if they are in the causal pathway of the disease," Ganz said. "We don't know what the FDA will ultimately think of this, but at least there are some features [to the panel] that should please them."
Ganz is not an employee of SomaLogic but sits on the company's medical advisory board, for which he does not receive any financial compensation. He is a longtime collaborator of the company, having worked with it on prior protein signatures for cardiovascular risk.
Ganz said he thought the panel could be particularly useful for pharma companies in evaluating the move from Phase II to Phase III clinical trials for cardiovascular drugs.
"You basically get all your experts in a room and review all your data and decide whether you are willing to commit to what is usually a few billion dollars for a drug in the cardiovascular space," he said. "Often that decision is based on surrogate markers. So, this would be, I would say, one of the most powerful surrogate markers for making that decision about going from Phase II to Phase III. That's how I would envision it being used."
Williams added that the company's efforts to develop evidence supporting the panel's use as a surrogate endpoint would also support its work on driving uptake of the panel for clinical applications such as helping doctors identify high-risk patients and monitor the effectiveness of treatment.
"If you look at the surrogate endpoints that are used to approve new drugs in drug development, they are also widely used in medical practice," he said. "So, this is a sweet spot in the intersection between our two businesses. If we can get a surrogacy claim and build that evidence, then we get two bangs for the buck — we get it for use in our life science business and we get it for use in healthcare."
The company has done a limited rollout of the test as one of its SomaSignal assays, which it offers as laboratory-developed tests. Nelson Trujillo, a cardiologist with Boulder Community Health and an author on the STM paper, is one of the physicians currently using the test. Trujillo told 360Dx previously he has primarily used the test to identify high-risk patients missed by traditional clinical measures.
Williams said he believed this was likely to be the most common use of the test clinically, noting that in the STM paper, most patients who had their risk level reclassified based on their panel score were up-classified to a higher risk level.
SomaLogic is currently using the panel in collaboration with several health systems to evaluate whether it is helpful for managing diabetic patients at high risk of cardiovascular disease. Williams said the company has started enrollment at four centers with a fifth soon to come on board for a roughly 2,000-subject randomized controlled study evaluating the panel in this population. The study will look at how the panel affects allocation of therapies as well as changes in patient risk over time along with health economic measures.
SomaLogic is also working with the company Qure to look at how the results of the test influence physician behavior.