Pancreatic cancer is the third leading cause of cancer death in the U.S., in part because many cases aren’t diagnosed until they are advanced. Bluestar Genomics Inc. wants to change that with its epigenomics technology which can detect early pancreatic cancer from a standard blood draw by analyzing cell-free DNA in plasma. Now, the FDA has provided a bump, granting breakthrough device designation to Bluestar’s noninvasive pancreatic cancer detection test in patients with new-onset diabetes.

According to the San Diego-based startup, of an estimated 60,000 patients diagnosed with pancreatic cancer in the U.S., nearly a fourth are found to have new-onset diabetes prior to receiving their cancer diagnosis. Bluestar believes its test could help to screen the roughly 1 million U.S. adults diagnosed annually with new-onset diabetes for pancreatic cancer, leading to early detection and intervention.

“Early detection is paramount for giving patients better treatment options to potentially improve outcomes,” said Kelly Bethel, chief medical officer of Bluestar Genomics. She noted that late diagnosis deprives patients of potentially curative options, such as surgery, that can increase survival rates.

Bluestar’s blood-based assay combines proprietary chemistries, bioinformatics and artificial intelligence with next-generation sequencing of DNA to not only pinpoint differences in sequencing but also analyze global patterns of epigenomic characteristics. 5-hydroxymethylcytosine (5hmC), the oxidized form of one of those epigenomic characteristics, has attracted attention for its impact on cellular processes and its relation to certain cancers.

Growing body of evidence

Bluestar’s 5hmC assay detects pancreatic cancer-derived fingerprints by evaluating 5hmC changes in DNA in disease-relevant genes.

In a study published in October in Nature Communications, Bluestar’s assay identified DNA-based epigenomic changes that could be used as new biomarkers to detect pancreatic cancers before they become untreatable.

The study included 307 subjects over age 40, 64 of whom had diagnosed pancreatic cancer. The results showed that 5hmC changes in 37 genes enabled the detection of pancreatic cancer in the cell-free DNA of participants with an area under he receiver operating characteristic (AU-ROC) curve of 0.92. The assay significantly outperformed CA 19-9, another blood test sometimes used to detect pancreatic tumor markers both in sensitivity and specificity, particularly in identifying stage I and II cancers.

The company plans to conduct a large clinical validation study to confirm the assay’s ability to detect pancreatic cancer in patients with new-onset diabetes.

“Currently, there are no screening methods to enable early detection of pancreatic cancer, while early, accurate detection has the potential to significantly improve prognosis by enabling better therapeutic options for patients,” said Samuel Levy, Bluestar’s CEO and chief scientific officer. “With FDA’s designation, combined with continued collaboration with top research institutions, our goal is to accelerate important clinical validation studies to bring out pancreatic cancer test to market in the coming years and continue to extend our efforts toward a multicancer screening test.”

Bluestar has already logged some miles toward its goal of a broad cancer screening test. In December, the company published work detailing the development of a genome-wide 5hmC map by characterizing the genomic distribution of 5hmC in 19 human tissues derived from 10 organ systems. Based on a study of 96 samples from the nervous, cardiovascular, digestive, reproductive, endocrine, respiratory, urinary, integumentary, skeletal and lymphatic systems, the map is the most thorough examination of 5hmC as a biomarker for cancer detection, according to the company.

A number of liquid biopsy companies are looking to bring multicancer tests to market, and pancreatic cancer is a key target, given its aggressive nature.

Base Genomics Ltd. is developing a DNA methylation-based blood test to screen for multiple early stage cancers, as well as to detect residual disease in patients previously treated for cancer. One of the cancers the technique has been shown to detect is pancreatic cancer. The London-based startup was recently snapped up along with Thrive Earlier Detection Corp. by Exact Sciences Corp. for $2.56 billion.

Grail Inc. plans to launch its Galleri liquid biopsy multicancer detection test as a laboratory-developed test in the second quarter of 2021. The company, whose $7.1 billion acquisition by Illumina Inc. is being challenged by the FTC, claims its test can detect a majority of pancreatic cancers at stage I.