Abstract Details

Title The Importance of Early Recognition and Treatment Initiation for Managing Alzheimer's disease: Subpopulation Analysis of the TRAILBLAZER-ALZ 2 Randomized Trial

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) S23 - Innovations in Dementia Treatment (1:48 PM-2:00 PM)

Poster/Presentation
Number 005

Background Compared with other contemporary early symptomatic AD studies, TRAILBLAZER-ALZ 2 (TB2) for donanemab included a broad and more clinically advanced population (Mini-Mental State Examination [MMSE] score 20-28 [inclusive]) with higher pathological disease burden (participants with low-medium and high tau and higher baseline amyloid, as measured by positron emission tomography [PET]).

Objective To assess efficacy and safety of donanemab in participants at earlier clinical (mild cognitive impairment [MCI]) and pathological (low-medium tau) stages of Alzheimer’s disease (AD).

Design/Methods A pre-specified subpopulation analysis of participants (placebo N=105; donanemab N=123) with MCI (baseline MMSE score ≥ 27) and low-medium tau PET burden from TB2 for efficacy and safety.

Results The MCI and low-medium tau subpopulation had relatively lower baseline plasma P-tau217 and similar amyloid burden (106 Centiloids) compared with the overall TB2 population (MCI or mild dementia due to AD with confirmed amyloid and tau pathology [low-medium or high tau PET level]). In the MCI and low-medium tau subpopulation, participants experienced 60% slowing of disease progression in the integrated Alzheimer's Disease Rating Scale (22% slowing in the overall population); 46% slowing in Clinical Dementia Rating Scale–Sum of boxes (29% slowing in the overall population) at Week 76. Comparable to the overall population, amyloid-related imaging abnormalities of edema or effusion occurred in 25.2% of participants in the MCI and low-medium tau subpopulation donanemab group. At Week 76, 71% of MCI and low-medium tau level participants completed treatment based on reduction of amyloid levels to below predefined thresholds on PET imaging; treatment completion frequencies were comparable in the overall population.

Conclusions Pre-specified analysis of the MCI and low-medium tau subpopulation suggests that initiating donanemab at an earlier clinical and pathological stage of disease may offer more favorable benefit/risk. The results reinforce importance of diagnosing and treating at the earliest symptomatic stages of AD.

Authors/Disclosures
Peter J. McAllister, MD, FAAN (New England Inst for Neurology and Headache) PRESENTER	Dr. McAllister has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for lilly. Dr. McAllister has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for abbvie. Dr. McAllister has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for lundbeck.
Raghavendra Vasudeva, PhD	Dr. Vasudeva has received personal compensation for serving as an employee of Lilly. Dr. Vasudeva has stock in Lilly.
Erin G. Doty, MD (Eli Lilly and Company)	Dr. Doty has received personal compensation for serving as an employee of Eli Lilly and Company, USA. Dr. Doty has stock in Eli Lilly and Company, USA.
Fan Yang, PhD	Ms. Yang has nothing to disclose.
Cynthia Evans (Eli Lilly & Company)	Cynthia Evans has received personal compensation for serving as an employee of Eli Lilly & Company. Cynthia Evans has stock in Eli Lilly & Company.
Jennifer Zimmer, MD	Dr. Zimmer has received personal compensation for serving as an employee of Eli Lilly & Company. Dr. Zimmer has stock in Eli Lilly & Company.
Ming Lu	Ming Lu has received personal compensation for serving as an employee of Eli Lilly and Company. Ming Lu has stock in Eli Lilly and Company.
Jasdip Singh, PharmD	Dr. Singh has received personal compensation for serving as an employee of Eli Lilly and Company. Dr. Singh has stock in Eli Lilly and Company.
John R. Sims, MD (Eli Lilly)	Dr. Sims has received personal compensation for serving as an employee of Eli Lilly and Company. Dr. Sims has stock in Eli Lilly and Company.

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