For 18 years, from memantine in 2003 until 2021, no new class of Alzheimer’s drug won approval. Then the FDA cleared aducanumab, sold as Aduhelm, by accelerated approval, and one of the most argued-over decisions in recent agency history followed.
The data were ambiguous, according to the drug-industry tracker TheraRadar. Three members of the FDA’s advisory committee resigned in protest, and Medicare limited coverage at first. Biogen withdrew the drug in 2024.
Two antibodies that did slow decline
Lecanemab, approved in 2023, and donanemab, approved in 2024, produced cleaner results. Lecanemab is the product of Eisai and Biogen, and donanemab is Eli Lilly’s. Both are anti-amyloid antibodies, and both slow cognitive decline by 25% to 35% over 18 months in early-stage patients with confirmed amyloid. A 27% slowing, TheraRadar notes, means patients on the drug declined 27% less than those on placebo. It does not mean the disease was cured.
Donanemab’s TRAILBLAZER-ALZ 2 trial enrolled 1,736 patients. The drugs carry a price in side effects. Brain swelling (ARIA-E) appeared in 12.6% of lecanemab patients against 1.7% on placebo, and in 24% of donanemab patients against 2.1%. Microhemorrhages showed up in 17.3% and 31.4% respectively, against 9% and 13.6% on placebo.
Why uptake is slow
Treatment means IV infusions, an amyloid PET or spinal fluid test to confirm eligibility, and regular MRI scans to watch for brain swelling and bleeding. Annual costs top $26,000. TheraRadar describes real-world uptake as slow. Cholinesterase inhibitors and memantine are still widely used, but they ease symptoms and do not change the course of the disease.
Roughly 7 million Americans have Alzheimer’s, and the number is projected to reach 13 million by 2050.
What failed, and what comes next
The field has a long record of late-stage failure. One in four Phase 3 trials in Alzheimer’s ends in termination, about three times the rate in diabetes or rheumatoid arthritis. Anti-tau antibodies such as semorinemab and zagotenemab have failed so far. Novo Nordisk’s EVOKE trials of oral semaglutide, which enrolled about 3,800 patients over two years, did not slow cognitive decline.
TheraRadar points to blood tests for p-tau217 as the most promising near-term development, since replacing amyloid PET scans with a blood draw could widen access to treatment. Companies investing in the area include Eli Lilly, Biogen, Eisai, Roche and Novo Nordisk. Patients and families weighing these drugs should talk to their doctor.
