GRAIL is a biotechnology company that develops tests for early cancer detection.
Can you introduce the Galleri test and explain the technology behind it?
The Galleri test, developed by Grail, is a multi-cancer early detection test based on significant insights from early experiments that identified unique DNA fingerprints in blood, consistent with cancer, in asymptomatic individuals. This innovation originated from a lab director’s observation during a non-invasive neonatal test, which unexpectedly indicated cancer in some cases. This test uses blood samples to identify genomic features and abnormal DNA fragments, employing a methylation platform for high sensitivity and specificity. It is designed to detect multiple types of cancer in individuals who show no symptoms, fundamentally changing cancer detection.
What is methylation and its role in the Galleri test?
Methylation in DNA provides a distinct fingerprint, which the Galleri test leverages to not only detect the presence of cancer but also to help identify the cancer's origin, whether it be the lung, pancreas, or another organ. This method involves examining methylation patterns in the blood to decode additional information provided by the epigenome. It marks a significant advancement in utilizing epigenetics to detect multiple cancers, thereby enhancing our ability to understand where exactly the cancer is stemming from within the body.
How broad is the field of application of the Galleri test? What type of cancers can it currently detect?
The Galleri test can identify over 50 types of cancers, focusing particularly on highly lethal cancers that lack existing screening modalities in population health, such as pancreatic, esophageal, and liver cancers. This capability represents a significant shift in medical practice, offering a broader screening range than the standard five single-cancer tests typically available. It extends the potential for early detection to a wider array of cancers, many of which are currently undetectable in early stages by other means. In fact, nearly 70% of cancer deaths are caused by cancers without recommended screening.
What are the test’s limitations?
While the test marks a significant advancement, it currently has limitations in detecting certain cancers, like brain tumors and some encapsulated or indolent cancers, such as testicular and slow-growing thyroid cancers. These limitations are due partly to biological barriers like the blood-brain barrier and the nature of certain tumors which do not shed DNA into the blood as readily. Ongoing research and development are aimed at overcoming these hurdles to enhance the test's applicability and accuracy.
What is the success rate of the Galleri test in detecting cancers?
The Galleri test demonstrates a positive predictive value of over 40%, which is a substantial improvement over most traditional single-cancer screenings that often show values below 10%.
Additionally, the test boasts a specificity greater than 99%, significantly reducing the rate of false positives. This high level of accuracy is crucial for minimizing unnecessary diagnostic procedures and is pivotal for the test’s integration into routine clinical practice.
Why is it recommended that the Galleri test be used in conjunction with traditional screenings?
The Galleri test is designed to be used in addition to existing standard of care screenings, such as mammograms, which are imaging-based and detect different types of cancers. This approach is vital because each method detects cancers in different ways; for instance, mammograms are particularly effective in identifying certain breast cancers, which the Galleri test may not detect as effectively. By integrating both methods, we can cover a broader spectrum of cancer types and stages, improving overall detection rates.
The FDA has not yet approved the Galleri test. What do you do to change that?
We are currently working closely with the FDA to achieve approval for the Galleri test, which has already received breakthrough designation. Our efforts include extensive clinical trials involving over 380,000 participants to ensure robust validation of the test's efficacy and safety. The test is already available in the U.S. on a prescription basis and has been accredited by CAP, CLIA, and New York State for our laboratory-developed test (LDT). We anticipate FDA approval following thorough review and demonstration of the test’s effectiveness in real-world settings.
Can you share some real-world outcomes of the Galleri test?
Since its implementation, the Galleri test has been instrumental in detecting cancers like cholangiocarcinoma and pancreatic cancer among asymptomatic individuals, reflecting its real-world impact beyond clinical trials. We have partnered with various health systems across the U.S., which has facilitated the integration of this test into everyday medical practice, significantly affecting patient outcomes. However, like all screening tests, the Galleri test has had instances of false positives, which we continuously study to improve accuracy. Our re-test program helps manage these cases by confirming or refuting initial findings, guiding further monitoring and investigation.
What progress has been made with getting the Galleri test covered by insurance providers?
We are making significant strides with insurance coverage for the Galleri test. Several insurers are currently providing coverage to their policyholders in the United States. We are also engaging in educational campaigns to help insurers understand the technology and its validation status. Additionally, we have recently initiated a partnership with CMS to conduct a real-world implementation study, the REACH study, targeting the Medicare population. This study not only aims to assess the test's effectiveness but also emphasizes reaching underserved communities.
Is the Galleri test currently available outside of the United States?
In the United Kingdom, we are collaborating with the NHS on a large-scale clinical trial involving 140,000 individuals, which is part of our efforts to integrate the test into their healthcare system. Results from this prevalent round screening are anticipated later this year, and there is potential for the program's expansion to include up to a million individuals. However, the test is not yet available in the European Union.
How are AI and machine learning utilized?
Machine learning is pivotal to the functionality of the Galleri test, influencing over 80% of our technology. These tools are essential for analyzing complex epigenetic patterns detected in the blood, which are indicative of cancer. Our technology evaluates more than a million CPG sites across the genome, utilizing machine learning to distill vast amounts of high-dimensional data into clinically-actionable information. This integration of AI allows for precise detection of multiple cancers, underscoring the transformative potential of this approach in cancer screening.
What are the key milestones Grail aims to achieve in the next three to five years?
Over the next few years, our primary goal is to secure broad adoption and FDA approval through our ongoing clinical trials and our breakthrough designation status. We are currently completing several major studies, including Pathfinder 2, and are eagerly anticipating the third round of annual screening results from the NHS-Galleri study. Concurrently, we are working with health systems to facilitate the test's current use by licensed prescribers, aiming to create a robust system that effectively manages the diagnostic process and significantly impacts patient outcomes through early detection.
