The New Alzheimer's Therapies are Not What One Would Call Successful

The first batch of immunotherapies demonstrated to be capable of clearing extracellular amyloid-β from the brain have performed poorly in late stage Alzheimer's patients. Data is beginning to emerge for their ability to modestly slow down the progression of the condition at earlier stages, however. This somewhat fits with the amyloid cascade hypothesis, in that it is evidence to support the idea that amyloid-β is no longer important to disease progression once the condition has reached the stage of becoming a feedback loop involving tau aggregation, chronic inflammation, and cell death.

Unfortunately, it isn't strong evidence for amyloid-β aggregation to be the major player in early Alzheimer's, building the foundation for that late stage disease environment to exist. When we say "modestly slow down the progression", it is worth noting that the reported effect size really isn't all that impressive, and it becomes reasonable to ask whether the side-effect profile and cost of the treatment is actually worth it. If amyloid-β were the major mechanism of early phases of Alzheimer's disease, wouldn't we see a much more profound benefit from clearance?

Expensive therapies that do little for patients are, unfortunately, business as usual in the fields of neurodegeneration and cancer. Pharma companies have become adept at colluding with regulators to eke out some declaration of marginal success from what is essentially a failed avenue of research and development. Much has been learned about the biology of the brain in the course of developing immunotherapies that can clear amyloid-β, and in principle clearance of protein aggregates is desirable even if immediate and obvious benefits are not realized, but at the same time this is quite clearly the wrong direction for Alzheimer's therapies.

New Alzheimer's drug slows cognitive decline by 35%, trial results show

A new Alzheimer's drug slowed cognitive decline by 35%, according to late-stage trial results, raising the prospect of a second effective treatment for the disease. Donanemab met all goals of the trial and slowed progression of the condition by 35% to 36% compared with a placebo in 1,182 people with early-stage Alzheimer's, the drugmaker Lilly said. It comes after trial results published last year showed that lecanemab, made by Eisai and Biogen, reduced the rate of cognitive decline by 27% in patients with early Alzheimer's.

In patients on donanemab, 47% showed no signs of the disease progressing after a year, according to a statement issued by Lilly. That compared to 29% on a placebo. The drug resulted in 40% less decline in the ability to perform activities of daily living, the company said. Patients on donanemab also experienced a 39% lower risk of progressing to the next stage of disease compared to those on a placebo.

However, the company also reported side-effects. Brain swelling occurred in 24% of those on donanemab, with 6.1% experiencing symptoms, Lilly said. Brain bleeding occurred in 31.4% of the donanemab group and 13.6% of the placebo group. Lilly also said the incidence of serious brain swelling in the donanemab study was 1.6%, including two deaths attributed to the condition and a third death after an incident of serious brain swelling.


I disagree. I think a 35 % slowdown in progression for a first of its kind therapy is pretty good.

Posted by: Antonio at May 12th, 2023 1:16 AM

I'm hoping this is the start to more and better treatments for this terrible disease.

35% is a good start, but, really, hoping it'll be well over 75% over next couple years with improved therapies.

Posted by: Robert at May 12th, 2023 10:44 AM

Plasmapheresis with albumin replacement showed already a 60% slowdown in the randomized AMBER trial. So 35% for the risk of brain bleeding, dying, and brain volume loss which is seen on anti-amyloid beta treatment is IMHO not that great.

Posted by: ML at May 13th, 2023 12:13 PM
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