NEW YORK – With a new name, new distribution deals, and a new clinical trial underway, ClearNote Health — formerly Bluestar Genomics — is entering the commercial market, starting with its pancreatic and ovarian cancer assays.
The San Diego-based company announced on Wednesday that it is rebranding to ClearNote Health to indicate its transition to the commercial phase of its business as it commercializes its first test for the early detection of pancreatic cancer. The firm also announced an international distribution agreement for the test with LifeStrands Genomics, which will distribute the test in Singapore and Malaysia.
Earlier this month, the company announced the initiation of its New Onset Diabetes Management for Earlier Detection (NODMED) trial, which will evaluate its epigenomic test's ability to identify pancreatic cancer in patients over the age of 50 who have recently been diagnosed with type 2 diabetes. The firm has started enrolling patients, with hopes for total enrollment of about 6,500, CEO Dave Mullarkey said in an interview. The company is collaborating with Thermo Fisher Scientific subsidiary contract research organization PPD to manage the trial and expects a data readout in the second half of 2024, Mullarkey noted.
David Halpert, principal investigator at JEM Research Institute and one of the participants in the NODMED study, said via email that patients recently diagnosed with type 2 diabetes have an eight times greater chance of developing pancreatic cancer than people without diabetes.
"With diabetes on the rise and really poor survival rates in pancreatic cancer, it is imperative that we utilize early detection to diagnose patients at stage I or II, when their cancer may still be treatable," he said. There is currently no noninvasive early detection of pancreatic cancer.
ClearNote's blood-based assays combine genomic and epigenomic information and quantitatively measure the 5-hydroxymethylcytosine (5hmC) biomarker, a key component of the methylation pathway that is "extremely informative in helping understand the process of when cells become cancerous," Mullarkey said. The biomarker is particularly well suited for early-stage detection because the company doesn't use "chemically damaging" bisulfite conversion and requires at a minimum 50 percent to 75 percent less input DNA than other approaches, meaning its tests require a lot less sequencing.
To run the as-yet-unnamed test, circulating tumor DNA is extracted from a patient's plasma and biotin tags are attached to the bases to modify hydroxymethyl groups on cytosine. Streptavidin-coated magnetic beads are used to enrich and then amplify the biotinylated DNA fragments that have 5hmC. Those fragments are then sequenced, providing data that is analyzed by an algorithm to produce an epigenetic signature that indicates the presence of cancer.
Earlier this year at the American Society of Clinical Oncology's GI cancer symposium, the firm shared results from a performance evaluation of the pancreatic cancer test. The assay showed 55 percent sensitivity and 98 percent specificity in a cohort of 1,433 patients with new-onset diabetes. Data presented in November at the American Pancreatic Association's annual meeting found the test had a sensitivity of 67 percent and specificity of 97 percent in 2,150 patients over the age of 50. The NODMED trial is intended to further expand the company's body of evidence.
The pancreatic cancer test is in the early stages of commercialization, with a physician experience program in the US intended to get the word out about the test and encourage clinicians of multiple specialties to utilize it. That program allows physicians to get experience ordering the test and working with the results, and ClearNote is actively recruiting and enrolling doctors for the program.
The firm is also having ongoing conversations with both private payors and the Centers for Medicare and Medicaid Services about reimbursement options — Mullarkey said there are opportunities to either leverage existing local coverage determinations or submit for a new coverage determination from CMS to garner coverage for the test, and that the company is currently making its final decision. Right now, the assay is offered as a laboratory-developed test, but the company is contemplating pursuing clearance from the US Food and Drug Administration, which issued breakthrough device designation for the test last year.
Outside of the US, ClearNote is partnering with diagnostic laboratories and entering into test send-out agreements, meaning labs in other countries will collect blood samples and send them to ClearNote's CLIA lab in San Diego for testing. However, Mullarkey noted that the option to replicate the lab's workflow and open additional laboratories in different regions is on the table and part of the firm's future plans.
While the LifeStrands distribution agreement is the only one that has been announced, Mullarkey said there are a number of global agreements with other partners in the final stages of confirmation and will be announced next year.
He also noted that right now, regulatory clearance in many other countries isn't necessary because the tests are being performed in the US. However, if the firm tries to secure government reimbursement in those countries, local trials or regulatory approvals may be needed.
In the US, the response to the pancreatic cancer test has been positive despite only being in the early stages of commercialization, Mullarkey said.
Elena Christofides, an endocrinologist who is participating in the physician experience program, said via email that she reached out to ClearNote to learn more about the test and plans to deploy it in 2023. Pancreatic cancer can be difficult to diagnose in early stages and is typically not found until there's little that can be done for the patient, so the actions that can be taken with early detection are "the only hope we can offer patients today."
Although the pancreatic cancer test is already being commercialized, ClearNote also has an ovarian cancer test nearly ready to launch. That test is in the final stages of validation and is expected to be commercially available in mid-2023, with plans to launch a clinical trial concurrently, Mullarkey said.
Beyond ovarian and pancreatic cancer, Mullarkey said the technology is being adapted across 15 different cancer types and works well in both detecting those cancers and identifying the tissue of tumor origin. A targeted multi-cancer test focused on high-risk patients is also in development with a potential launch date in the second half of 2023, he said.
Regardless of the cancer being detected, the test and fully automated workflow remain the same, he noted. The assay analyzes the whole genome and profiles the entire 5-hydroxy methylome, which is fed into a specific algorithm that analyzes different regions of the genome and performs the particular analysis needed to detect the signal for the cancer of interest.
While the company's primary focus is on early cancer detection, its technology has broader potential applications. ClearNote has multiple ongoing pharmaceutical and biotechnology collaborations to determine the technology's ability to monitor response to therapies and detect cancer recurrence, Mullarkey said. The company is currently working on pilot studies to explore the full benefit of its technology, he added.
As the firm transitions to its commercial era, the focus will remain on the "highest mortality cancers in patients at high risk for those cancers and particularly where no early effective detection tools exist today," Mullarkey said. "These are the areas with the highest unmet need."