Nordic Bioscience, a leading biomarker company, today announced that the internationally recognized New England Journal of Medicine Evidence (NEJME) has published research that further establishes and positions its extracellular matrix (ECM) biomarker, PRO-C6, as a potential next-generation biomarker for trial enrichment in patients with heart failure with preserved ejection fraction (HFpEF). The paper is entitled “Endotrophin, a collagen VI formation-derived peptide, in Heart Failure” and can be found here: https://evidence.nejm.org/doi/full/10.1056/EVIDoa2200091
The studies, conducted in collaboration with Bristol Myers Squibb and the University of Pennsylvania, combined analyses of six independent cohorts of HFpEF patients from around the globe which are being evaluated with the PRO-C6 biomarker. HFpEF is a highly heterogenous syndrome greatly affected- and driven by underlying comorbidities, with no current treatments that selectively reduce morbidity and mortality. It poses one of the greatest unmet medical needs today, and its prevalence is projected to increase in the coming years.
This discovery has led to the issuing of an official Letter of Support from the U.S. Food and Drug Administration (FDA), acknowledging and supporting the further study of the PRO-C6 biomarker assay for trial enrichment inHFpEF:
“The plan to study the PRO-C6 biomarker assay for prognostic enrichment is consistent with the FDA’s guidance document ‘Enrichment Strategies for Clinical Trials to Support Approval of Human Drugs and Biological Products’. The ability to identify patients at greater risk for events can reduce the sample size needed to show an effect in an outcome study,” excerpt from the official FDA Letter of Support.
The PRO-C6 biomarker assay has been transferred to the Roche Diagnostics cobas® e platform, increasing accuracy in sample measurements, enabling future IVD-based decision making. This is an important step in making sure that clinical samples are utilized in the best way possible and to enable patient segregation and drug decision-making in clinical trials.
Morten A. Karsdal, Chief Executive Officer of Nordic Bioscience said:
“Having the PRO-C6 biomarker assay on the Roche Diagnostics cobas® e platform is an important step for increasing the utility of the biomarker and paving the way for clinical decision-making in a disease area with significant complications where better diagnostic and prognostic biomarkers are required. Seeing the data validated and published in the NEJM Evidence journal is a great scientific achievement.”
“Identifying and developing therapies for the broad HFpEF population has been a challenge. Many clinical trials have failed due to the inability to identify patient subgroups and match them to potential therapies,” said David Gordon, vice president, Cardiovascular & Fibrosis Discovery Biology, Bristol Myers Squibb, a GHFC leader. “Data on PRO-C6 gathered thus far and the letter of support from the FDA reinforce the potential of this biomarker to be used in routine cardiology practice to help identify individual patient risk, prognosis, and even potentially guide therapeutic decisions.”
Fibrosis is acknowledged to be a key driver of HFpEF pathology, contributing to ventricular stiffness and reduced function. Improving understanding of how fibrosis and extracellular matrix (ECM) turnover are regulated could be the key to unlocking novel treatments for HFpEF patients.
The PRO-C6 biomarker assay measures type VI collagen formation, which is known to be upregulated when fibroblasts are activated. This increased activity causes fibrosis. Furthermore, when type VI collagen is formed, a bioactive molecule, endotrophin, is released, which is known to be involved in pathological processes that could contribute to HFpEF pathology, including inflammation and fibrosis. The PRO-C6 biomarker assay therefore describes key pathological features of HFpEF, highly associated with risk of outcome, that are not currently described by other biomarkers in the field.
Study lead and corresponding author Julio Chirinos, MD, PhD, an associate professor of Cardiovascular Medicine at the Perelman School of Medicine at the University of Pennsylvania said,
“PRO-C6 represents a highly promising biomarker for assessing risk in heart failure with preserved ejection fraction, which is an extremely important clinical problem,” said “We urgently need novel approaches for risk stratification and precision therapeutics for this common form of heart failure, and this research moves us in the right direction.”