An experimental Alzheimer’s disease treatment from Eli Lilly removed toxic plaques from the brain more effectively than Biogen’s approved drug Aduhelm in a small study of people with early dementia symptoms.
The study results, unveiled Wednesday at a medical conference, position Lilly’s treatment as a more potent clearer of the sticky clumps of protein in the brain that have long been linked to Alzheimer’s. But the data’s significance won’t be clear until Lilly reports the outcome of a larger trial testing donanemab’s effect on the cognitive and functional decline brought on by the disease.
Notably, though, donanemab’s greater plaque clearance was not associated with higher rates of a side effect that’s associated with drugs like it and Aduhelm. The side effect, known as ARIA, is in the spotlight following the deaths of two participants in a clinical trial of another experimental Alzheimer’s treatment called lecanemab, which is also designed to clear brain plaques. Full results from that trial were presented Tuesday at the same medical meeting, the Clinical Trials on Alzheimer’s Disease conference.
Lilly’s study is also significant as the first head-to-head comparison of two treatments that target the plaques in early Alzheimer’s disease. These plaques, consisting of a protein called amyloid beta, have been the focus of decades of research, but until recently every drug development effort had failed.
The trial, called TRAILBLAZER-ALZ 4, enrolled 148 patients aged 50 to 85 years old with early symptomatic Alzheimer’s disease. Data showed that, after six months, treatment with Lilly’s drug had cleared amyloid from the brain in about 38% of treated patients, compared to only roughly 2% of those given Biogen’s Aduhelm. Average reduction versus baseline levels was just over 65% among study participants given donanemab and 17% in participants on Aduhelm.
In the trials that supported Aduhelm’s approval, treatment did eventually result in similarly high amyloid clearance as donanemab, but not until an assessment at 18 months.
Twenty-five percent of patients in the donanemab group experienced ARIA, or amyloid-related imaging abnormalities, with only 2.8% reported as symptomatic. Among the Aduhelm group, ARIA was reported in 26% of treated patients, with 4.3% symptomatic. In both groups, the symptomatic cases were related to ARIA that involved brain swelling, or edema.
“This was ... the first study to obtain ARIA rates side by side using identical methods for ARIA assessment in the same patient population, demonstrating the ability to disconnect rate of plaque clearance from rate of ARIA incidence,” said Mark Mintun, Lilly’s vice president of pain and neurodegeneration R&D, in a company statement.
Lilly is currently running a large Phase 3 trial of donanemab that’s designed to measure the drug’s cognitive and functional benefit. Data are expected in mid-2023.
A decision from the Food and Drug Administration on approval of donanemab could come before then, though, as earlier this year Lilly applied for an accelerated clearance based on mid-stage study results that showed strong amyloid clearance and hinted at a clinical benefit.
Donanemab’s comparison versus Aduhelm could factor into the FDA’s decision, as the agency granted accelerated approval to Biogen’s medicine based on how well it cleared amyloid plaques, establishing a new regulatory standard.
Eisai, which is leading development of lecanemab in partnership with Biogen, has also applied for a speedy approval of its drug and expects a verdict in early January.
Neither lecanemab nor donanemab may initially be used widely if approved by the FDA next year. Doubts over Aduhelm’s effectiveness led to low uptake of the medicine and spurred Medicare, which covers many of the Alzheimer’s patients that would be eligible for treatment, to restrict reimbursement of anti-amyloid drugs to clinical trials.
Executives at Eisai and Lilly expect they could win broader coverage with more convincing trial results than Aduhelm had, but that will take time and, possibly, a standard approval from the FDA.
Eisai already has the data it needs in hand, presenting on Tuesday detailed results from a study that showed lecanemab slowed patients’ cognitive and functional decline by 27% more than placebo. While that benefit is viewed as modest at best by some doctors, it sets a bar for donanemab and other drugs that might follow.