Eli Lilly announced Wednesday that its tau PET ligand, flortaucipir, aka AV1451, met co-primary endpoints in a small Phase 3 trial. This autopsy study apparently confirmed, postmortem, that flortaucipir had predicted tau pathology and Alzheimer’s disease among 67 volunteers who were approaching the end of their lives when they signed up.

“Based on ongoing research it appears tau PET could have clinical potential for both diagnostic utility and for disease staging,” said Gil Rabinovici, Stanford University, California. “But in terms of the result of this trial, we have to wait to see.” Lilly plans to present data from the trial at the upcoming Clinical Trials on Alzheimer’s Disease conference in Barcelona.

Eric Reiman, Banner Alzheimer’s Institute, Phoenix, considers the study important. “Avid has been a leader in correlating antemortem tau imaging with postmortem tau pathology. This is not easy to do, but is required by the FDA to prove that the PET biomarker meets standards of truth,” he told Alzforum. “I look forward to seeing the data.” Banner researchers participated in the study.

The A16 trial enrolled 156 volunteers who were believed to have at most six months to live and who consented to donating their brains for autopsy. There seems to have been no requirement that the volunteers have a diagnosis of AD. Each volunteer was going to undergo at least one flortaucipir PET scan. Co-primary outcomes were a pattern of tracer uptake that corresponded to neurofibrillary tangle accumulation consistent with Braak stage V/VI, and a pattern consistent with high levels of AD neuropathologic change as defined by National Institute on Aging-Alzheimer's Association (NIA-AA) criteria. Five independent readers interpreted each scan.

The release claims the tracer met endpoint criteria for 67 of the 156 enrolled. A spokeswomen from Lilly told Alzforum that the 67 satisfied the trial’s power calculation, so Lilly did not need to wait to analyze data from additional participants.

Even if the outcome holds up, this data would not prove the tracer reliably quantifies neurofibrillary tangles in people at earlier Braak stages. “Most people consider Braak stages III and IV clinically meaningful, and ideally a tau tracer should be useful in those stages, as well,” said Rabinovici.—Tom Fagan

Comments

  1. This study represents a landmark achievement, in that PET data acquired with the most widely used tau tracer have now been compared on an individual basis with postmortem findings in 67 participants. As was the case with amyloid PET, the Avid team has led the way in large-scale postmortem correlation, and they deserve congratulations for these efforts. Specific findings from this unprecedented sample will likely be a valuable contribution, particularly as they may relate to earlier stages of tauopathy that are getting increased focus in the setting of AD prevention trials. The details will likely reward careful scrutiny.

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References

External Citations

  1. A16 trial

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