Abstract Details

Title The Lecanemab Clarity AD Open-label Extension in Early Alzheimer’s Disease: Initial Findings from the 48-month Analysis

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) S1 - New Perspectives on Alzheimer's Therapeutics (1:48 PM-2:00 PM)

Poster/Presentation
Number 005

Objective To report the initial findings up to 48 months from the ongoing Clarity AD open-label extension (OLE) study.

Background Lecanemab is a humanized IgG1 monoclonal antibody that binds with high affinity to amyloid-beta (Aβ) protofibrils. In the 18-month, phase 3 Clarity AD study, lecanemab demonstrated amyloid reduction and cognition and function decline slowing in participants with early symptomatic Alzheimer’s disease (AD).

Design/Methods Clarity AD is an 18-month, randomized study (Core) followed by an OLE phase in individuals with early AD. Clinical (CDR-SB, ADAS-Cog14, and ADCS-MCI-ADL) outcomes and safety were evaluated from OLE data out to 48 months. Continued lecanemab treatment in the OLE beyond the 18 months from the Core study was compared to a matched control from Alzheimer's Disease Neuroimaging Initiative (ADNI) data. Subgroup analyses were conducted for participants with no/low baseline tau. Efficacy assessments were also summarized as the percentage of participants who had ‘no decline’ or had ‘improvement’ from Core baseline at each timepoint.

Results Overall, 1734 participants were treated with lecanemab across the Core and OLE. Across clinical endpoints, lecanemab-treated participants continued to benefit through 48 months and delay progression through 48 months compared to ADNI matched control, with differences in CDR-SB increasing over 18 months (0.52), 36 months (1.01), and 48 months (1.75). Consistent rates of clinical stability or improvements were observed across assessments regardless of baseline tau levels, with the highest rates of improvements observed for the no/low tau group at 48 months (CDR-SB:no decline:69%, improvement:56%; ADAS-Cog14:no decline:51%, improvement:51%; ADCS MCI-ADL:no decline:64%, improvement:58%). ARIA rates were low and similar to ARIA rates on placebo after 6 months.

Conclusions In Clarity AD, the observed increasing treatment difference with ongoing lecanemab treatment in participants treated through 48 months versus ADNI matched placebo data is consistent with a durable disease-modifying effect, with no new safety signals.

Authors/Disclosures
Christopher van Dyck, MD PRESENTER	Dr. van Dyck has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai. Dr. van Dyck has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. van Dyck has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ono. Dr. van Dyck has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS. Dr. van Dyck has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cerevel. Dr. van Dyck has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB.
Reisa A. Sperling, MD (Brigham and Women'S Hospital)	Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AbbVie. Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AC Immune. Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acumen. Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alector. Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biohaven. Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Myers Squibb. Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Nervgen. Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Oligomerix. Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Prothena. Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ionis. Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Vaxxinity. An immediate family member of Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. An immediate family member of Dr. Sperling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. The institution of Dr. Sperling has received research support from Eli Lilly. The institution of Dr. Sperling has received research support from Eisai. The institution of Dr. Sperling has received research support from NIH.
David Li (Eisai)	David Li has received personal compensation for serving as an employee of Eisai.
Michio Kanekiyo, MS	Mr. Kanekiyo has received personal compensation for serving as an employee of Eisai Inc. Mr. Kanekiyo has stock in Eisai Co Ltd..
Shobha Dhadda	Shobha Dhadda has received personal compensation for serving as an employee of Eisai Inc.
Steven M. Hersch, MD, PhD (Eisai Inc.)	Dr. Hersch has received personal compensation for serving as an employee of Eisai Inc.. Dr. Hersch has stock in Voyager Therapeutics. The institution of an immediate family member of Dr. Hersch has received research support from NIH. Dr. Hersch has received intellectual property interests from a discovery or technology relating to health care.
Michelle Gee, PhD	Dr. Gee has nothing to disclose.
Michael C. Irizarry, MD (Eisai, Inc)	Dr. Irizarry has received personal compensation for serving as an employee of Eisai, Inc..
Lynn D. Kramer, MD, FAAN (Eisai Inc.)	Dr. Kramer has received personal compensation for serving as an employee of Eisai Inc. Dr. Kramer has received personal compensation in the range of $1,000,000+ for serving as an officer or member of the Board of Directors for Eisai Co., Ltd..

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