Between 2003 and 2021, drugmakers spent an estimated $42.5 billion trying to build an Alzheimer’s treatment that did more than ease symptoms. Nothing worked. Then, in 2022, a trial of a drug called lecanemab finally did.
A century of symptom relief
Alois Alzheimer described the plaques and tangles of the disease in 1906. For most of the time since, medicine could only soften its edges. Donepezil, sold as Aricept, reached patients in 1996, and memantine, sold as Namenda, followed in 2003. Both modestly help memory and attention for months, sometimes a year. Neither slows the loss of neurons underneath.
The industry placed its bet on amyloid, a sticky protein that builds into plaques. The logic looked sound: rare gene mutations that raise amyloid production guarantee early-onset disease. But the results kept coming back empty. Pfizer and Johnson & Johnson’s bapineuzumab showed no efficacy in more than 2,400 patients. Eli Lilly’s solanezumab failed four phase 3 trials spread over a decade. Between 2002 and 2012 the failure rate for Alzheimer’s candidates hit 99.6%, the worst of any disease in medicine.
In 2021 the FDA gave Biogen and Eisai’s aducanumab, sold as Aduhelm, a contested conditional approval. It was later removed from the market, earlier in 2024.
Clarity AD and the turn
The lecanemab study, Clarity AD, enrolled 1795 people with early Alzheimer’s and split them evenly between the drug, given every two weeks, and a placebo. At 18 months, lecanemab had cut clinical decline on the CDR-SB scale by 27%, a difference of -0.45 points. The gap showed up as early as six months. “The lecanemab Clarity study results prove the amyloid hypothesis,” said Haruo Naito, Eisai’s chief executive.
The FDA first cleared the drug, marketed as Leqembi, in January 2023 under its accelerated pathway, then granted traditional approval that July. Teresa Buracchio of the agency’s neuroscience office called it “the first verification that a drug targeting the underlying disease process of Alzheimer’s disease has shown clinical benefit.”
Lilly’s donanemab, sold as Kisunla, came next. Its TRAILBLAZER-ALZ-2 trial ran across 277 sites in 8 countries and enrolled 1736 patients, 860 on the drug and 876 on placebo, dosed every four weeks for up to 72 weeks. The FDA approved it in July 2024 for adults with mild cognitive impairment or mild dementia and confirmed amyloid. It is the first of the class with evidence supporting a stop once plaques clear, which can mean fewer infusions and a lower bill.
Limits that remain
The National Institute on Aging is plain about this: there are currently no known interventions that will cure Alzheimer’s. The studies showed slower decline in some participants over 18 months, not a halt. Both drugs can cause amyloid-related imaging abnormalities, swelling or bleeding in the brain, so doctors are advised to watch with MRI scans. Medicare Part B covers part of the cost for patients who meet set criteria.
R. Scott Turner, who directs the Memory Disorders Program at Georgetown University, welcomed the second option. “A more competitive landscape for MCI and AD treatments may also lead to price competition,” he said, “thereby permitting greater access to treatment for the millions of affected individuals.”
Patients should talk to their doctor about whether either drug fits their stage of the disease.
Sources
- How Is Alzheimer's Disease Treated? | National Institute on Aging
- FDA Approves Eli Lilly's Donanemab for Early Symptomatic Alzheimer Disease | NeurologyLive – Clinical Neurology News and Neurology Expert Insights
- Alzheimer's: 20 Years, 99% Failure, $42 Billion, Two Drugs | TheraRadar
- Lecanemab Shows Highly Statistically Significant Reduction of Clinical Decline in Early Alzheimer Disease | Pharmacy Times
- FDA Grants Traditional Approval to Lecanemab as Therapy for Early-Stage Alzheimer Disease | NeurologyLive – Clinical Neurology News and Neurology Expert Insights
