Beach ghosts and donanemab
Yesterday evening as sundown approached, I looked out a window on the west side of our house and saw a startling headless reflection looking back enquiringly at me. The optics were easily explained: I was standing illuminated by bright sunlight from the front, the room behind me was dark, and the beach grass in front of me was mostly in the shadows. My legs were blocked from the sunlight by the window sill, so my lower legs disappeared in the reflected image. I’m not sure what happened to my head. I grabbed my iPhone to record the moment, a moment that oddly invoked a supernatural combination of trepidation and exhilaration.
As for more earthly things, the FDA informed Eli Lilly in March that its application for full approval of the anti-amyloid monoclonal antibody donanemab was to be paused for further review. Donanemab is the most effective medication yet in completely removing beta-amyloid plaques from the brain, but it has only a modest 35% benefit in slowing cognitive impairment. Subjects with the mildest disease had the best response to donanemab, and a trial in asymptomatic subjects who have amyloid plaques in their brains but no cognitive impairment is underway. Most Alzheimer’s experts interviewed for a NeurologyToday article released yesterday felt that donanemab should eventually be approved, but they agreed that the details of who should and shouldn’t receive it and other issues of use should be clarified. For example, carriers of the APOE-4 allele are at increased risk of having symptomatic, sometimes fatal swelling and/or bleeding in the brain when given donanemab or similar drugs. Should all APOE-4 carriers be excluded from treatment? If not, who will pay for the added surveillance such as frequent MRI scans that will be needed for APOE-4 carriers. If we exclude all APOE-4 carriers, we will have excluded 60% of people living with Alzheimer’s disease. I agree that the FDA is right to pause the approval of donanemab before opening what may become a neurological Pandora’s box. Let’s be sure we get it right.
A “neurological Pandora’s box” is simply more than this cerebrum can fathom. I am certainly glad and thankful that you are at the front lines, fighting this noble battle, my dear Dr. Gibbs.