Grail Inc.’s multi-cancer blood test, Galleri, failed to hit its primary goal in a large-scale National Health Service trial, triggering a steep sell-off that cut the company’s stock price in half. The NHS-Galleri study was designed to show that routine blood screening could catch cancers early enough to reduce late-stage diagnoses across a broad population. Instead, the results fell short of that threshold, raising hard questions about whether the technology is ready for widespread clinical use.
NHS Trial Misses Its Central Target
The Galleri test was built on an appealing premise: a single blood draw could screen for more than 50 cancer types by detecting fragments of tumor DNA circulating in the bloodstream. The NHS-Galleri trial, one of the largest randomized screening studies ever conducted in the United Kingdom, set out to prove that this approach would meaningfully shift cancer diagnoses from late stages to earlier, more treatable ones. That endpoint was chosen deliberately. Peer-reviewed research published in the Journal of Medical Screening had established that reductions in late-stage cancer incidence correlate strongly with mortality reductions across historical screening trials, making stage shift a defensible surrogate for lives saved.
Yet the trial did not deliver the stage shift researchers expected. According to BBC coverage, the multi-cancer blood test missed its key goal in the NHS trial. Earlier data from the study, published in The Lancet, had offered some encouraging signals, including what was described as a substantial reduction in Stage IV cancer diagnoses and increased Stage I and II detection of deadly cancers, according to a Lancet analysis. That same work pointed to a four-fold higher cancer detection rate in the screened group. The tension between those interim findings and the trial’s failure to meet its primary endpoint is the central puzzle confronting researchers and investors alike.
Why High Specificity Was Not Enough
Part of the answer lies in the gap between laboratory performance and real-world screening effectiveness. A systematic literature review conducted by UK health authorities and published in the NIHR evidence library found that the Galleri test, evaluated in the PATHFINDER study, achieved a specificity of approximately 99.5%. That figure sounds impressive, and in a clinical setting it means the test rarely flags healthy people incorrectly. But the same review pegged the test’s positive predictive value at roughly 43.1%, meaning that among those who received a positive result, fewer than half actually had cancer. In a screening context applied to millions of people, that rate generates a large volume of false alarms, each requiring costly and anxiety-inducing follow-up imaging and biopsies.
The review also documented that sensitivity, the test’s ability to correctly identify people who do have cancer, varied widely depending on the tumor type. Some aggressive cancers with high cell-free DNA shedding were caught reliably; others, particularly early-stage or slow-growing tumors, slipped through. That uneven performance across dozens of cancer types helps explain why a population-level trial measuring overall stage shift could fall short even when the test performs well for certain individual malignancies. The NIHR technology assessment program explicitly flagged these limitations, cautioning that existing evidence was insufficient to support confident conclusions about population-level screening benefit.
Investors Absorb a 50% Stock Collapse
Financial markets reacted swiftly and severely. Grail’s shares plunged nearly 50% on Friday after the company disclosed the trial results. The sell-off reflected not just disappointment over the data but also deep uncertainty about Grail’s path to regulatory approval in both the United States and the United Kingdom. The company had been seeking clearance based in part on the NHS-Galleri trial as a flagship demonstration of clinical utility, and the missed endpoint weakens that case considerably.
The scale of the decline, separately confirmed by Wall Street Journal market reporting, wiped out billions in market value in a single session. For a company that had positioned itself as the leader in multi-cancer early detection, the loss signals that investors now see a much longer and more uncertain road to commercialization. Grail will likely need additional trial data or a redesigned study to rebuild confidence among regulators and payers, and that process could take years.
The Screening Paradox for Patients
For the millions of people who had hoped a simple blood test might catch hidden cancers before symptoms appear, the trial result carries a more personal sting. The promise of multi-cancer early detection rests on the idea that finding tumors at Stage I or II, rather than Stage III or IV, gives patients far better odds of survival. That logic is sound in principle, and the meta-regression evidence supporting the link between stage shift and mortality reduction is well established across decades of screening research for individual cancers like breast, colorectal, and lung cancer.
But applying that framework to a single test spanning more than 50 malignancies introduces new layers of complexity. A modest improvement in early-stage detection for some cancers can be offset by missed cases in others, or by overdiagnosis of tumors that might never have caused symptoms. Patients who test positive face a cascade of follow-up scans and biopsies, some of which will ultimately reveal no cancer at all. Meanwhile, those who receive a negative result may be falsely reassured even though the test is known to miss certain tumor types and early lesions. Clinicians and ethicists must weigh these trade-offs carefully before recommending population-wide screening.
What Comes Next for Regulators and Researchers
The regulatory path forward is now more complicated. Agencies in both the UK and US had been watching the NHS-Galleri trial closely as a potential template for evaluating multi-cancer tests. With the primary endpoint missed, regulators are likely to demand stronger evidence that Galleri can reduce cancer deaths rather than simply detect more tumors. That could mean longer, larger trials powered for mortality outcomes, or more targeted studies focusing on high-risk groups where the balance of benefits and harms may be more favorable. Health technology bodies, drawing on work such as the NIH-linked evidence infrastructure, are expected to scrutinize not only clinical performance but also cost-effectiveness and health-system impact.
Researchers, for their part, are already parsing the NHS data to understand where Galleri performed best and where it fell short. One possibility is that multi-cancer blood tests will first find a role as adjunct tools for patients with elevated risk, such as heavy smokers or those with strong family histories, rather than as universal screens. Another is that future versions of the technology will incorporate additional biomarkers or machine-learning refinements to boost sensitivity without sacrificing specificity. Whatever the direction, the combination of sobering trial results and a dramatic market repricing, highlighted in both Reuters and Wall Street Journal updates, underscores that the road from promising concept to proven public-health tool is longer than many investors – and patients – had hoped.
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*This article was researched with the help of AI, with human editors creating the final content.
