NEW YORK (GenomeWeb) – Myriad RBM said this week that it has signed a deal with Sanofi to measure cardiovascular risk biomarkers in subjects participating in the pharma firm's Phase III trial for its type II diabetes drug lixisenatide.
The agreement follows a 2012 collaboration between Myriad RBM, Sanofi, and Canada's Population Health Research Institute (PHRI) that identified a set of protein markers associated with cardiovascular events or death in type II diabetes patients. Both projects are part of a larger effort to identify and develop a suite of protein biomarkers that could potentially be used for the management of type II diabetes and related conditions including retinopathy and chronic kidney damage, Myriad RBM President Ralph McDade told GenomeWeb this week.
Under the deal, Myriad RBM will measure a panel of 46 protein markers in around 5,300 serum samples from the Evaluation of Lixisenatide in Acute Coronary Syndrome (ELIXA) trial. The 46 markers are linked to cardiovascular risk and microvascular damage, which can lead to the retinopathy and nephropathy associated with type II diabetes.
The markers were first identified in the Outcome Reduction with Initial Glargine Intervention (ORIGIN) study, a seven-year, 12,500-participant trial Sanofi launched in 2005 to study its Lantus (insulin glargine) agent, comparing use of the drug in patients with impaired fasting glucose, impaired glucose tolerance, or early type II diabetes versus the standard of care for these patients.
Upon completion of the trial in 2012, Sanofi collaborated with the PHRI and Myriad RBM to identify protein markers for cardiovascular risk in 8,400 of these subjects using the latter's DiscoveryMAP assay panel to measure levels of 237 proteins in patient blood.
That effort identified 10 markers linked to an increased risk of myocardial infarction, stroke, or death and an additional five markers that, when added to the original 10, further improved prediction of death. It also identified a panel of nine markers that slightly improved the ability to predict progression to a composite outcome that, in addition to myocardial infarction, stroke, and death, included heart failure hospitalization or revascularization.
The study also identified a group of markers that were associated with microvascular damage, McDade said.
"[Sanofi] first went through the data from ORIGIN looking at cardiovascular outcomes," he said. "And then we asked them to continue going through it because we were very interested in the kidney damage [markers]."
In total, the researchers identified the 46 markers covering cardiovascular and microvascular risk that they now plan to measure in patients from the ELIXA trial. The study will provide, if not validation, then "certainly a strong verification" of the cardiovascular risk markers, McDade said, noting that it will be the third large-scale study using the markers to assess cardiovascular risk in type II diabetes patients.
McDade said that Myriad RBM is perhaps "equally excited about the retinopathy and nephropathy" markers. He noted that advances in the treatment of these conditions increases the usefulness of protein biomarkers for predicting and detecting them. He added that they could potentially be packaged into a panel for helping doctors better manage their type II diabetes patients.
McDade said that Myriad RBM's interest in microvascular risk markers dates back at least a decade to work the company did with Novartis, but that at that time there was little doctors could do for patients, even if they were shown to be at heightened risk for microvascular damage.
"The one thing a doctor could do was put a person on an ACE [angiotensin converting enzyme] inhibitor to reduce hypertension," he said. However, he added, in the US, this is standard practice for most type II diabetes patients regardless of their specific risk for microvascular damage.
Today, antifibrotic drugs exist that can be used to mitigate microvascular damage, McDade said. "So the thought is you can use these blood-based patterns to tell the physician that a person not only has type II diabetes but that they are also on the path to the [kidney] transplant list."
"[The protein markers] could be used as a sort of companion or complementary diagnostic [to determine] if a person is a candidate for one of these drugs," he said.
This, McDade said, would allow Sanofi to present physicians with a full portfolio of drugs and biomarkers for managing type II diabetes patients.
"They have their insulin [Lantus], they have their GLP-1 inhibitor [lixisenatide], they already have ramipril, which is their ACE inhibitor, and now if they have one of these antifibrotics. Then they have a portfolio they can take to the endocrinologist and say, 'Look, we have everything we need to manage these patients, and here are these blood [protein] patterns that show you we can identify them before the severe damage actually happens,'" he said. (Sanofi has partnered with Regulus on development of antifibrotic therapies.)
The question then becomes, how might they commercialize the biomarker assay, McDade said, adding that Myriad RBM is in frequent discussions with Sanofi about potential commercialization strategies.
"The question is whether they will partner with a big diagnostic company or with somebody like Myriad," he said, adding that he was hopeful for his firm's prospects due to the fact that large diagnostics firms like Roche are also Sanofi competitors in the pharma business.
"I think we have a real shot at being the diagnostic provider at least for this initial testing [of the assay] and release into the market," he said.
He noted that any commercialization process would likely involve partnering with PHRI, given that some of the intellectual property is shared with that institution.
"We have IP we filed specifically on the kidney and retinopathy side, so the microvascular [markers]," McDade said. "And there is the Canadian group that was the original group that directed the ORIGIN study. They have some joint IP on the cardiovascular markers. All together it is a pretty nice portfolio."