{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T10:11:12Z","timestamp":1787911872631,"version":"build-2784847793"},"reference-count":53,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,2,8]],"date-time":"2025-02-08T00:00:00Z","timestamp":1738972800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmacy"],"abstract":"<jats:p>Objective: The purpose of this review is to examine the potential role of donanemab-azbt in the treatment and management of early-stage Alzheimer\u2019s disease (AD), with a focus on its efficacy, safety, and clinical relevance based on data from key clinical trials. Data Sources: A comprehensive literature search of PubMed was conducted using relevant keywords such as \u201cdonanemab\u201d, \u201cAlzheimer\u2019s disease\u201d, \u201cKisunla\u201d, \u201cTRAILBLAZER clinical trials\u201d, and \u201camyloid-related imaging abnormalities (ARIA)\u201d. Additional data were extracted from clinical trial records (clinicaltrials.gov), conference abstracts, and product monographs. Study Selection and Data Extraction: Only English-language studies conducted in human populations were included. Clinical trials and peer-reviewed studies detailing the efficacy, safety, and mechanistic insights of donanemab-azbt were prioritized. Data Synthesis: Key findings from the TRAILBLAZER series of clinical trials highlighted the potential of donanemab-azbt in slowing cognitive and functional decline in early-stage AD: (1) TRAILBLAZER-ALZ (Phase 2): This trial focused on participants with intermediate levels of tau protein. Results demonstrated a statistically significant slowing of cognitive and functional decline. (2) TRAILBLAZER-ALZ 2 (Phase 3): A large-scale, randomized, double-blind, placebo-controlled study confirmed the efficacy of donanemab-azbt in reducing amyloid plaque accumulation and cognitive decline. Key results included a 35% slowing of decline on the Integrated Alzheimer\u2019s Disease Rating Scale (iADRS) and a 36% slowing on the Clinical Dementia Rating-Sum of Boxes (CDR-SB). Additional secondary outcomes showed improvements in activities of daily living and reduced risk of disease progression. (3) TRAILBLAZER-ALZ 3: This ongoing trial is evaluating donanemab\u2019s potential in delaying or preventing Alois Alzheimer in cognitively normal individuals with amyloid plaques, broadening the scope of early intervention strategies. (4) TRAILBLAZER-ALZ 4: A head-to-head comparison with aducanumab revealed superior amyloid plaque clearance with donanemab. (5) TRAILBLAZER-ALZ 5: Currently recruiting, this trial aims to evaluate safety and efficacy across diverse populations with varying tau levels and comorbidities. (6) TRAILBLAZER-ALZ 6 (Phase 3b): This trial investigates modified dosing regimens to reduce ARIA while maintaining efficacy, particularly in populations with genetic risk factors like ApoE \u03b54 homozygotes. Relevance to Patient Care and Clinical Practice: Donanemab-azbt represents a promising treatment option for patients with early-stage AD. It specifically targets and reduces amyloid beta plaques, a hallmark of the disease, potentially slowing progression and preserving cognitive function. However, its administration requires careful patient selection, including genetic testing for ApoE \u03b54 status, to mitigate risks of ARIA. Furthermore, the findings emphasize the importance of close monitoring during treatment. Conclusions: Donanemab-azbt offers a new avenue for managing early-stage AD, showing promise in reducing amyloid burden and slowing cognitive decline. While its efficacy and safety have been demonstrated in clinical trials, further research is essential to validate long-term outcomes, assess effectiveness across diverse populations, and refine dosing strategies to minimize side effects. With continued investigation, donanemab-azbt could significantly impact the clinical landscape of AD treatment.<\/jats:p>","DOI":"10.3390\/pharmacy13010023","type":"journal-article","created":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T05:53:22Z","timestamp":1739166802000},"page":"23","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Targeting Amyloid Pathology in Early Alzheimer\u2019s: The Promise of Donanemab-Azbt"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2923-4842","authenticated-orcid":false,"given":"Nadia","family":"Khartabil","sequence":"first","affiliation":[{"name":"School of Pharmacy, West Coast University, Anaheim, CA 92801, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayda","family":"Awaness","sequence":"additional","affiliation":[{"name":"School of Pharmacy, West Coast University, Anaheim, CA 92801, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.cell.2019.09.001","article-title":"Alzheimer Disease: An Update on Pathobiology and Treatment Strategies","volume":"179","author":"Long","year":"2019","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"141","DOI":"10.2217\/nmt-2022-0037","article-title":"The amyloid-\u03b2 pathway in Alzheimer\u2019s disease: A plain language summary","volume":"13","author":"Hampel","year":"2023","journal-title":"Neurodegener. 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