Working Towards Lowering ARIA Rates, Reducing Amyloid Plaques: Marwan Sabbagh, MD, FAAN


The behavioral neurologist at the Barrow Neurological Institute detailed the significance of low rates of ARIA found in lecanemab, and the direction of anti-amyloid therapies in the future. [WATCH TIME: 4 minutes]

WATCH TIME: 4 minutes

"Since we know the ARIA rates tend to occur on the front end, in the first 90 to 180 days [of treatment], I think what you’ll see is more MRIs, more vigilance, and more surveillance at beginning. Fortunately, most of them resolved without treatment. But my point is, we’re going to want to address a lot of these concerns at the beginning of the study and not let that get out of control."

Over the past few years, there has been a surge within the Alzheimer disease (AD) drug development space to produce anti-amyloid therapies that lower the amount of amyloid-ß in an individual’s brain. The hope is that removing plaques will keep brain cells working normally for longer. In June 2021, the FDA approved aducanumab (Aduhelm; Biogen), an anti-amyloid monoclonal antibody for patients with early-stage AD; however, the therapy’s approval was met with controversy, as one of the main trials supporting its application did not show full efficacy and the therapy itself was linked to several amyloid-related imaging abnormalities (ARIA).

Lecanemab (Biogen & Eisai), a humanized monoclonal antibody that eliminates toxic amyloid-ß protofibrils, looks to follow in the steps of aducanumab as the next approved treatment for patients with early AD. In the phase 3 Clarity AD study (NCT01767311), one of the supporting trials for its new drug application, investigators reported an ARIA-edema rate of 12.5% for those on lecanemab vs 1.7% of those on placebo. Symptomatic ARIA-E occurred at a rate of 2.8% in the lecanemab group and 0.0% in the placebo group.

Currently under FDA review, a decision on lecanemab is expected to come on January 6, 2023. To learn more about the ARIA incidence of lecanemab, including how it might be handled if approved, NeurologyLive® sat down with Marwan Sabbagh, MD, FAAN. Sabbagh, a behavioral neurologist at the Barrow Neurological Institute, provided insight on whether the approach to lecanemab differs from other anti-amyloid therapies, as well as the significance of the growing treatment toolbox for patients with AD.

1. Irizarry M, van Dyck C, Sabbagh M, Bateman R, Cohen S. Clarity AD: A phase 3 placebo-controlled, double-blind, parallel-group, 18-month study evaluating lecanemab in early Alzheimer disease. Presented at: CTAD Conference, November 29-Dec 2.
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