Where the future of Alzheimer's drugs is heading

• Eli Lilly's drug candidate donanemab could soon become the third anti-amyloid monoclonal antibody — which targets a buildup of proteins in the brain thought to contribute to Alzheimer's — to receive some kind of FDA approval, all in the past three years.
• "Donanemab and related drugs caused a splash. But I think that now we're kind of moving on," said Keith Vossel, director of the Mary S. Easton Center for Alzheimer's Research and Care at UCLA.
• "The clinical uptake of these drugs has been slower than expected [because of] the moderate benefit that is offered, so that gives scientists more motivation to find news ways to slow the disease course."

Driving the news: An FDA advisory committee voted unanimously earlier this month in support of donanemab, concluding that its benefits outweigh its risks.

• The FDA had called for an outside review earlier this year after some patients enrolled in a clinical trial experienced brain swelling, bleeding and other adverse events.
• But Leqembi, the Alzheimer's drug from Biogen and Eisai approved a year ago, offers a somewhat cautionary tale: Many patients are still deciding that the drug isn't worth it, for one reason or another, as evidenced by its muted commercial success after launch. Sales have been picking up this year, however.

That's not to say that donanemab won't make a difference to some patients, as clinical trial data show it can slow cognitive decline by about a third.

• That may be enough to make Eli Lilly billions of dollars.
• But some scientists remain skeptical that the drug's effects, while measurable in clinical trials, will be noticeable to patients.

Where it stands: As of January, there were 127 drugs being assessed in 164 clinical trials against Alzheimer's, according to a study published in an Alzheimer's-focused journal. Three-quarters aim to modify the disease versus treat its symptoms, and a quarter were in Phase 3.

• Less than a fifth of total drugs under development — and 22% of those in Phase 3 trials — target amyloid.
• By comparison, a third of the drugs in late-stage trials target chemical messengers in the brain known as neurotransmitters.
• The drugs in Phase 3 trials target 10 categories of biological processes, and there are two Phase 3 trials looking at preventing the disease altogether.

One alternative target getting a lot of attention is tau, another protein that some scientists suspect may play a greater role than amyloid in cognitive decline.

The bottom line: "I think we're probably seeing something that is very close to the maximum benefit from an anti-amyloid therapy," said Matthew Schrag, a Vanderbilt neurology professor and director of the Cerebral Amyloid Angiopathy Clinic.

• "This is not the beginning. This is decades of development and many, many, many, many failed trials have led to something that is just barely detectable. And what we're learning is beta amyloid is just one component of a very complicated disease."