Donanemab 350mg/20ml solution for infusion vials

Amyloid-β (Aβ) plaques and aggregated tau are two core mechanisms that contribute to the clinical deterioration of Alzheimer’s disease (AD). Recently, targeted-Aβ plaque reduction immunotherapies have been explored for their efficacy and safety as AD treatment. This systematic review critically reviews the latest evidence of Donanemab, a humanized antibody that targets the reduction in Aβ plaques, in AD patients. Comprehensive systematic search was conducted across PubMed/MEDLINE, CINAHL Plus, Web of Science, Cochrane, and Scopus. This study adhered to PRISMA Statement 2020 guidelines. Adult patients with Alzheimer’s disease being intervened with Donanemab compared to placebo or standard of care in the clinical trial setting were included. A total of 396 patients across four studies received either Donanemab or a placebo (228 and 168 participants, respectively). The Aβ-plaque reduction was found to be dependent upon baseline levels, such that lower baseline levels had complete amyloid clearance (<24.1 Centiloids). There was a slowing of overall tau levels accumulation as well as relatively reduced functional and cognitive decline noted on the Integrated Alzheimer’s Disease Rating Scale by 32% in the Donanemab arm. The safety of Donanemab was established with key adverse events related to Amyloid-Related Imaging Abnormalities (ARIA), ranging between 26.1 and 30.5% across the trials. There is preliminary support for delayed cognitive and functional decline with Donanemab among patients with mild-to-moderate AD. It remains unclear whether Donenameb extends therapeutic benefits that can modify and improve the clinical status of AD patients. Further trials can explore the interplay between Aβ-plaque reduction and toxic tau levels to derive meaningful clinical benefits in AD patients suffering from cognitive impairment.

Abstract licence: CC BY 4.0

INTRODUCTION: Donanemab (Kisunla) is a humanized IgG1 monoclonal antibody specifically targeting a modified form of β-amyloid found predominantly within plaques (characterized as N-terminal pyroglutamate Aβ). Recently, it has gained approval for the use in early-stage Alzheimer's disease (AD) encompassing mild cognitive impairment due to AD or mild AD with confirmed brain amyloid pathology. AREAS COVERED: This drug profile discusses donanemab's function, clinical effectiveness, safety, tolerability, health economics, access challenges, and future prospects. This article is based on systematic review that was derived from PubMed. EXPERT OPINION: Donanemab is the third monoclonal antibody introduced for the treatment of individuals in the early stage of AD. While critical dialog continues regarding the potential impacts and role of antibody therapies, its approval signifies considerable progress in addressing the underlying pathology of AD. The authors are confident in the potential of antibodies against Aβ as a promising treatment option and foresee exciting advancements. However, further research is needed on trials extending beyond 18 months of follow-up, postmarketing surveillance, and the application of donanemab in combination with existing treatments and lifestyle interventions. Additionally, significant knowledge gaps and implementation limitations persist and must be addressed.

Abstract licence: CC BY-NC-ND 4.0

BackgroundLecanemab and donanemab are the first anti-amyloid monoclonal antibodies (mAbs) clinically available as disease-modifying therapies for Alzheimer's disease (AD). However, it remains unclear whether their treatment effects differ across demographic, clinical, or genetic subgroups.ObjectiveThis systematic review aimed to explore how patient characteristics modify the efficacy, safety and humanistic outcomes of anti-amyloid mAbs lecanemab and donanemab in patients with early AD.MethodsA systematic search of MEDLINE, Embase, Scopus, Web of Science, and Cochrane Library was conducted from database inception to July 30th, 2025, using a combination of keywords and Medical Subject Heading terms relating to lecanemab and donanemab. Meta-analyses were conducted for safety outcomes where sufficient data was available.ResultsSixteen studies representing six randomised clinical trials (total N = 5633) were included. Both lecanemab and donanemab showed the greatest slowing of cognitive decline in White/Caucasian patients and apolipoprotein E4 (ApoE4) non-carriers. Amyloid-related imaging abnormalities with edema/effusion (ARIA-E) and microhemorrhages (ARIA-H) were more prevalent in ApoE4 carriers. The risk of ARIA-E was 2.19 times higher (95 %CI:1.91-2.50) and ARIA-H was 3.45 times higher (95 %CI:1.35-8.72) in ApoE4 carriers versus non-carriers. Statistically significant improvements in health-related quality of life were observed with lecanemab in ApoE4 heterozygous participants and in those aged 65-74 years.ConclusionsThe efficacy and safety of anti-amyloid mAbs in AD may differ based on patients' demographic and genetic factors. These findings highlight the potential for personalised treatment strategies and inform national drug policies. Further research is needed to evaluate long-term outcomes and address under-studied patient populations.SummaryThe efficacy and safety of lecanemab and donanemab varied across patient subgroups, including age, sex, race/ethnicity and genetic factors such as ApoE4 genotype status. The risk of ARIA was higher in ApoE4 carriers, particularly the homozygous.

Abstract licence: CC BY

BackgroundThe management of Alzheimer's disease has shifted toward disease-modifying therapies aimed at delaying disease progression rather than focusing solely on symptomatic treatment. This study summarizes the latest evidence regarding the benefits and harms of anti-Alzheimer's disease drugs.MethodsWe conducted a comprehensive review of randomized controlled trials from PubMed, Embase, Cochrane Library, Web of Science databases, and other sources up to April 2025. Two researchers independently reviewed the literature and analyzed the data. A network meta-analysis was performed using Review Manager version 5.3 and Stata version 18.0 to calculate mean differences (MDs) and 95% confidence intervals (CIs) for direct and indirect comparisons. Treatment efficacy was evaluated using the Surface Under the Cumulative Ranking Curve (SUCRA). Bias was assessed using the Revised Cochrane Risk of Bias Tool version 2.0, and publication bias was analyzed with funnel plots.ResultsThe network meta-analysis included 23 randomized controlled trials with 16,010 participants, evaluating nine pharmacological interventions ranging from traditional symptomatic therapies to four United States Food and Drug Administration- and National Medical Products Administration-approved disease-modifying therapies, notably anti-amyloid beta monoclonal antibodies. Aducanumab significantly improved ADAS-cog scores compared with placebo (MD -5.97, 95%CI -10.33, -1.61; SUCRA: 93.0%) and demonstrated notable improvements in ADCS-ADL scores (MD 4.99, 95%CI 2.27, 7.72; SUCRA: 98.6%). Memantine ranked highest for neuropsychiatric symptoms (SUCRA: 80.8%). Aducanumab also had the highest SUCRA for CDR-SB (91.5%) and showed moderate superiority in MMSE scores (MD 3.55, 95%CI 1.35, 5.75; SUCRA: 98.2%).ConclusionSymptomatic treatments, especially memantine for neuropsychiatric symptoms, remain effective. However, the network meta-analysis indicates that, for patients with mild cognitive impairment or mild Alzheimer's disease, aducanumab demonstrates the greatest potential for cognitive and clinical improvement (MMSE, ADAS-cog, ADCS-ADL), despite associated risks such as adverse events and amyloid-related imaging abnormalities linked to disease-modifying therapies. Lecanemab provides moderate benefits, while donanemab appears less effective. Thus, clinicians should apply disease-modifying therapies cautiously and individually, carefully balancing potential risks and benefits for each patient.Systematic review registrationPROSPERO [CRD42025637730], https://www.crd.york.ac.uk/PROSPERO/.

Abstract licence: CC BY