The majority of patients with early-stage disease Alzheimer’s disease (AD) had stable or improved cognition over roughly 1 year of treatment with lecanemab (Leqembi), a real-world analysis showed.

The data, from an interim subanalysis of the ongoing LEADER retrospective cohort study, showed that about 84% of patients with mild cognitive impairment (MCI) or mild dementia due to AD either maintained their baseline disease stage or improved after an average of 375 days of therapy.

“The results from the LEADER interim subanalysis, along with data from Clarity AD, suggest that lecanemab may help patients remain stable for a longer period, with the potential for improvement in some individuals,” study investigator Courtney Adams, PhD, US Medical Affairs & Strategy, Neurology, Eisai, Inc., Nutley, New Jersey, told Medscape Medical News.

“The Clarity AD extension data also suggest that earlier initiation and longer treatment duration are associated with greater clinical benefit. Taken together, real-world and trial data indicate that lecanemab could play an important role in helping preserve daily functioning over time,” she added.

The study was presented on December 1 at the 18th Clinical Trials on Alzheimer’s Disease (CTAD) Conference.

Need for Real-World Data

Lecanemab received US approval for early AD based on randomized clinical trial evidence showing slowed cognitive decline. While those findings established efficacy under controlled conditions, clinicians and researchers have been eager for real-world data that might reflect typical patient experiences in varied clinical practices and a broader demographic group.

The LEADER study was designed to meet that need by gathering retrospective data from geographically diverse neurology clinics across the US.

The interim analysis included 177 patients (102 with MCI and 75 with mild AD) from nine centers who received at least seven lecanemab infusions. Over the roughly 1 year of follow-up, disease stage (improved, stable, progressed) was determined by clinician judgement, which included a comprehensive review of all available information, including Montreal Cognitive Assessment (MoCA) and functional activities questionnaire scores, as well as patient and caregiver feedback.

From baseline to last follow-up, 12 patients (7%) improved, 137 (77%) remained stable, and 28 (16%) progressed. “While these descriptive real-world findings cannot be directly compared to clinical trial results, they align directionally with Clarity AD,” Adams said. 

MoCA scores — available for a subset of patients — generally paralleled the clinician-assigned categories: patients who improved showed numerical increases, those who were stable maintained their scores, and those who progressed declined, she noted.

Who Benefits Most?

Adams noted that patients who improved on lecanemab tended to have longer treatment duration, received more doses of the drug, had fewer comorbidities and concomitant medications, and showed numerically lower baseline functional impairment compared with those who were stable or progressed.

“Longer exposure is associated with better outcomes in many chronic progressive conditions, and it is reasonable to consider that greater exposure to lecanemab may contribute to more favorable outcomes, including improvement,” Adams said.

Safety findings were consistent with prior clinical trial data. Amyloid-related imaging abnormalities (ARIA) occurred in 23 patients overall, with similar rates across outcome groups.

Edema- or effusion-type ARIA (ARIA-E) was reported in 8% of patients overall; two cases were symptomatic cases. Hemorrhagic ARIA (ARIA-H) occurred in 6% of the cohort — all were asymptomatic.

‘Real Clinical Value’

Reached for comment, Shaheen Lakhan, MD, PhD, neurologist and researcher based in Miami, told Medscape Medical News, “[t]his is the kind of real-world evidence clinicians need. It provides a clear signal that stability in early AD is achievable and meaningful.”

“The question is no longer whether antiamyloid therapies work outside trials, but how to deliver them earlier and more consistently to the patients most likely to benefit,” said Lakhan, who wasn’t involved in the study.

“In a condition where doing nothing almost always leads to decline, seeing 84% of patients maintain or even improve their disease stage over roughly a year on lecanemab represents real clinical value,” Lakhan said.

The fact that only 7% improved “should not be dismissed,” he said. “These are individuals moving from mild dementia back to MCI, a functional shift that matters deeply to patients and families. Improvement is not the norm in a neurodegenerative disease, so the presence of any improvement is noteworthy,” Lakhan told Medscape Medical News.

In his view, “stability will remain the most realistic expectation for most patients, but this analysis shows that improvement is possible in the right clinical phenotype. It also confirms that safety signals such as ARIA remain within expected ranges.”

Lakhan said the key takeaway from the study is that in a disease defined by steady decline, even maintaining function represents meaningful benefit — and lecanemab appears to help patients do that.

The study was supported by Eisai. Several authors disclosed having relationships with the company. Aisen has ongoing research collaborations with Eisai, Lilly, Cognition Therapeutics and consults with Merck, Roche, Genentech, AbbVie, Biogen, ImmunoBrain Checkpoint, AltPrep, Bristol Myers Squibb, Johnson & Johnson, New Amsterdam, and Neurimmune. Lakhan reported no disclosures.