Early Alzheimer’s Treatment with Lecanemab Shows Reduced Disease Progression

The efficacy of lecanemab in treating individuals with early Alzheimer’s disease and how long the monoclonal antibody medication could be effective were discussed in two presentations at the American Academy of Neurology annual meeting in Denver. Positive results were reported in an abstract and a poster about the use of the intravenous infusion therapy that targets amyloid in the brain.

“These studies are refining our understanding of the impact of lecanemab treatment on clinical outcomes and biomarker outcomes,” said Michael Irizarry, MD, MPH, senior vice president of clinical research and deputy chief clinical officer for the Neurology Business Group, Eisai. “I think the field can build on this as we continue to develop more and better treatments for Alzheimer’s disease.”

Both presentations were based on substudies of the Phase 3 clinical trial Lecanemab Clarity AD: Quality-of-Life Results from a Randomized, Double-Blind Phase 3 Trial in Early Alzheimer’s Disease. The trial followed 1,795 individuals with early Alzheimer’s disease who were treated with open-label lecanemab or placebo. The researchers concluded that the treatment reduced markers of amyloid and resulted in moderately less decline in measures of cognition and function than placebo.

Efficacy and Biomarker Results with Lecanemab

The poster presentation, Lecanemab for the Treatment of Early Alzheimer’s Disease: Extension of Efficacy and Biomarker Results from Clarity AD and the Downstream Implications of Targeting Tau, was based on a tau PET substudy of 342 patients, Dr. Irizarry said. Tau PET looks at the location of tangles in the brain and the intensity of neurofibrillary tangles.

The cohort was similar to the overall population, he said. The results showed that lecanemab slowed the spread of tangles, particularly in the medial temporal lobe, which is involved in memory. The sub­study also staged participants by the levels of tau in the brain, with 40% having low tau and 60% intermediate tau.

In some clinical trials, people with lower levels of tau are excluded because they progress more slowly and so it may be harder to see a treatment effect, Dr. Irizarry explained. This substudy identified a treatment effect in patients with low and intermediate levels of tau.

“Overall, what this suggested is that if you treated people in the earlier pathological stages of symptomatic Alzheimer’s disease, you may be able to improve or stabilize longer,” he said. “This was an exploratory substudy, so we will be looking at this more carefully in another clinical trial we have ongoing, the AHEAD 3‒45 Study, which is treating people who are cognitively unimpaired but already have elevated amyloid in the brain.”

Efficacy Extension Further Urges Early Alzheimer’s Diagnosis and Treatment

The abstract, Lecanemab for the Treatment of Early Alzheimer’s Disease: The Extension of Efficacy Results from Clarity AD, was an open-label extension substudy that evaluated whether treatment benefits were maintained beyond the 18-month Phase 3 trial. It also compared the progression of the disease of patients in both the lecanemab cohort and the placebo cohort, who later started to receive lecanemab treatment.

At 6 months, that separation between the cohorts was maintained so the placebo group who started late on lecanemab didn’t catch up to the lecanemab group. However, the disease progression of both groups was similar, but parallel, Dr. Irizarry said.

“This suggests that if treatment is delayed, then people just lose or decline to a level they don’t catch up on had they been started earlier on lecanemab,” he said. “Overall, that highlights to us the importance of early recognition, diagnosis, and treatment of early Alzheimer’s disease so people with symptoms of cognitive decline should be evaluated and confirm that elevated amyloid. (They should be given) the opportunity to (get) the offered treatment with lecanemab if they are eligible for it.”

Disclosures: The Lecanemab Clarity AD study was sponsored by Eisai, Inc., and Biogen. Dr. Irizarry reported receiving personal compensation for serving as an employee of Eisai, Inc.