New Alzheimer’s Trial to Combine Anti-Amyloid and Anti-Tau Therapies to Arrest Disease Progression


A new study will combine an Alzheimer’s medication that slows disease progression in some patients with two drugs that target disease-driving proteins to see whether their effects can be amplified. This will be the first trial to test drugs acting on amyloid and tau for patients with late-onset Alzheimer’s, the most common type of dementia.

The trial will recruit 900 participants with early Alzheimer’s at UCSF and other sites nationwide. It is funded by a $151 million grant from the National Institute on Aging, part of the National Institutes of Health.

The grant was awarded to neurologist Adam L. Boxer, MD, PhD, the trial's principal investigator and project leader and endowed professor in memory and aging in the UCSF Department of Neurology. The trial is co-led by Keith Johnson, MD, professor of radiology and neurology at Harvard Medical School.

In the Alzheimer’s Tau Platform (ATP) clinical trial, researchers will evaluate the effects of two anti-tau therapies and an anti-amyloid therapy, such as lecanemab (Leqembi), which was approved by the Food and Drug Administration in January 2023 after demonstrating a 27% reduction in global impairment compared with placebo.

Lecanemab and related drugs clear amyloid and have also been shown to reduce tau. But drugs that specifically target tau may be more effective because their levels and locations correlate more closely with symptoms.

Multiple medications may create synergistic effect


“The ATP trial represents the next era in Alzheimer’s treatment developments, since it will use a combination of therapies that may have additive or synergistic effects,” said Boxer, who also directs UCSF's clinical trials program for Alzheimer’s disease and frontotemporal dementia as well as the Neurosciences Clinical Research Unit. “In addition to potentially better clinical results, this treatment approach is constructed on a novel, more efficient clinical trial design.”     

Final details of the trial are pending, but researchers will likely recruit participants age 60 or older with asymptomatic Alzheimer’s disease or mild cognitive impairment, confirmed by tau blood tests, PET scans and cognitive testing.

Trial may exclude placebo, due to ethical considerations

Participants will be divided into multiple parallel groups and randomized to receive the anti-amyloid medication with or without one or two of the tau medications for a duration of 24 months. It is not yet known whether a small subgroup will receive a placebo, with some researchers questioning whether placebo use is ethical in this population.

The study will conclude with cognitive testing, brain imaging, and blood level tests of tau and related proteins.

According to Boxer, the trial is expected to save up to 50% in costs because it replaces multiple trials testing each tau therapy alone followed by combination trials and it requires substantially fewer participants.

Eventually, other drugs may be added to the “rolling platform” format of the trial. These include medications that target other disease drivers, such as metabolic dysfunction or inflammation. It is believed that trials such as this one will lead to “clinically meaningful advances at a much faster rate than in the past,” Boxer said.

Reviewing 30 years of research

Boxer recently cowrote a review article examining the past and future of clinical trials for Alzheimer’s disease. He suggests that moving forward, the challenge will be to develop more efficacious therapies with greater efficiency.

“Novel trial designs, including those testing multiple different therapies at the same time either in comparison to one another [umbrella trials] or in combination with one another, or those testing the same therapy in multiple diseases [basket trials], will accelerate clinical development,” he said. “Better diversity and inclusivity are needed, and blood-based biomarkers may help to improve access for medically underserved groups. Incentivizing innovation in both academia and industry through public-private partnerships, collaborative mechanisms and creating new career paths will be critical to build momentum.”

Neurology and neurosurgery research and treatment take place within the UCSF Weill Institute for Neurosciences.

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