Kisunla (donanemab-azbt) / Eli Lilly - LARVOL DELTA

Alzheimer's Disease: Treatment Challenges for the Future. (PubMed, J Neurochem) - "These antibodies, lecanemab and donanemab, mark a turning point for our understanding of the disease pathogenesis and for the treatment of this prevalent disorder. This review discusses what they imply for disease pathogenesis and what is needed to progress from the current imperfect therapies toward safe and better, disease halting therapies. The research over the next period will involve drug development, largely aimed at reducing the side effects of the anti-amyloid therapies, biomarker and genetic research to try and identify patients earlier in the disease process, and neuropathological research in individuals who have received treatment to try and understand the pathological substrates of the continuing clinical decline in the disease."

Journal • Review • Alzheimer's Disease • CNS Disorders

Taiwan NHI excludes coverage for new Alzheimer's drug Kisunla (Focus Taiwan) - "Taipei, July 31 (CNA) Kisunla, a newly approved Alzheimer's drug in Taiwan, will not be covered by the National Health Insurance (NHI) system, while coverage for Leqembi, another Alzheimer's treatment approved this year, is still under review, a health official overseeing the NHI system said Thursday...Kisunla has already been reviewed by an expert panel, which concluded that although the drug has completed Phase 3 clinical trials, the follow-up period for users was too short and its long-term benefits remain unclear, National Health Insurance Administration (NHIA) Director-General Shih Chung-liang...said in a legislative session."

Reimbursement • Alzheimer's Disease

Lilly's Kisunla (donanemab-azbt) showed growing benefit over three years in early symptomatic Alzheimer's disease (PRNewswire) - P3 | N=1,736 | TRAILBLAZER-ALZ 2 (NCT04437511) | Sponsor: Eli Lilly and Company | "Eli Lilly and Company...announced results from the long-term extension (LTE) of the Phase 3 TRAILBLAZER-ALZ 2 study showing that participants treated with Kisunla (donanemab-azbt) demonstrated slowing of decline, a benefit that continued to grow over three years compared to an untreated external cohort from the Alzheimer's Disease Neuroimaging Initiative (ADNI)...Kisunla benefit continued to grow over three years for participants treated in the study compared to those in the matched ADNI group. Kisunla reduced cognitive decline by -0.6 at 18 months and then -1.2 at 36 months on the Clinical Dementia Rating Sum of Boxes (CDR-SB) in patients initially treated with Kisunla in the core study compared to the ADNI group; Earlier initiation of Kisunla reduced the risk of progression to the next stage of disease by 27% on the Clinical Dementia Rating-Global Score (CDR-G)..."

P3 data • Alzheimer's Disease

The structural foundations of anti-amyloid-β immunotherapies: Unravelling antibody-antigen interactions in Alzheimer's disease treatment. (PubMed, J Alzheimers Dis) - "BackgroundAnti-amyloid-β (Aβ) immunotherapies are emerging as treatments for Alzheimer's disease (AD).ObjectiveThis review examines the structure-activity relationships of anti-Aβ therapeutics tested in phase 3 trials.MethodsWe analyzed crystallographic data and molecular models to elucidate the Aβ binding mechanisms of donanemab, lecanemab, aducanumab, bapineuzumab, gantenerumab, solanezumab, and crenezumab.ResultsLecanemab recognizes minimally degraded Aβ missing 1-2 residues, avoiding common Aβ in circulation and further degraded material sequestered in plaques. This focal point may account for the significant cognitive effects of lecanemab. The structure of aducanumab suggests a broadly neutralizing role has evolved for natural immunity to AD."

Journal • Review • Alzheimer's Disease • CNS Disorders • Vascular Neurology • APOE

How many sites are enough? a novel, site-based power analysis method for real-world registry studies of anti-amyloid monoclonal antibodies. (PubMed, JAR Life) - "Simulated ALZ-NET and AD-DMT registry settings using prevalence and ARIA frequencies from published lecanemab and donanemab trials. Conventional methods risk underestimating site requirements by ignoring caseload heterogeneity. Our simulation framework provides more realistic estimates and, crucially, quantifies the substantial efficiency gains from strategic recruitment, serving as a flexible tool to optimize registry design."

Journal • Real-world evidence • APOE

The Drug Update: Recent drug approvals, summer 2025 edition. (PubMed, Nurse Pract) - "This article highlights the following new medications: donanemab-azbt (Kisunla), nalmefene injection (Zurnai), epinephrine nasal spray (neffy), palopegteriparatide (Yorvipath), xanomeline and trospium chloride (Cobenfy), and sulopenem etzadroxil/probenecid (Orlynvah). Additionally, this article highlights the recent approval of obstructive sleep apnea as a new indication for tirzepatide (Zepbound) and chronic obstructive pulmonary disease as a new indication for dupilumab (Dupixent)."

Journal • Addiction (Opioid and Alcohol) • Allergy • Alzheimer's Disease • Chronic Obstructive Pulmonary Disease • CNS Disorders • Endocrine Disorders • Hypoparathyroidism • Immunology • Obstructive Sleep Apnea • Psychiatry • Pulmonary Disease • Respiratory Diseases • Schizophrenia • Sleep Disorder

What to know about 2 new Alzheimer’s disease drugs approved in Singapore (Straits Times) - "Tackling Alzheimer’s disease in Singapore received a boost earlier in 2025, when the authorities approved two new drugs for the neurodegenerative disease. Although these drugs - lecanemab and donanemab - cannot cure or reverse the effects of Alzheimer’s, they have been shown to slow the progression of the disease, which accounts for almost 70 per cent of dementia cases worldwide....Findings from the clinical trial of lecanemab, published in the New England Journal of Medicine, showed that it slowed decline for people with early Alzheimer’s disease by about 27 per cent to 37 per cent. Meanwhile, results from donanemab’s Phase 3 clinical trial, published in the Journal of the American Medical Association, showed that the drug slowed cognitive decline by about 20 per cent to 29 per cent."

Approval • Alzheimer's Disease

Donanemab receives positive opinion from the Committee for Medicinal Products for Human Use (CHMP) in early symptomatic Alzheimer's disease (PRNewswire) - "Eli Lilly and Company...announced today that the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion recommending donanemab for the treatment of early symptomatic Alzheimer's disease in adults with confirmed amyloid pathology who are apolipoprotein E ε4 (ApoE4) heterozygotes or non-carriers. The European Commission is expected to make a regulatory decision on donanemab in the coming months....The positive opinion was primarily based on clinical trial data from the TRAILBLAZER-ALZ 2 clinical trial demonstrating that donanemab significantly slowed cognitive and functional decline and reduced the risk of progressing to the next clinical stage of disease, as well as the TRAILBLAZER-ALZ 6 clinical trial which evaluated a modified titration dosing schedule."

CHMP • EMA approval • Alzheimer's Disease

Practical Guide of the Korean Association for Geriatric Psychiatry to Anti-Amyloid Monoclonal Antibody Therapy for Alzheimer's Disease: Focused on Lecanemab. (PubMed, J Korean Med Sci) - "This publication represents the first nationwide roadmap in Korea to support clinicians in the appropriate integration of monoclonal antibody therapies for AD. By combining scientific rigor, operational feasibility, and ethical sensitivity, it aims to promote safe and responsible adoption of disease-modifying treatment across various clinical settings."

Journal • Review • Alzheimer's Disease • CNS Disorders • Dementia • Psychiatry

Safety of switching from lecanemab to donanemab in 20 consecutive patients with Alzheimer's disease. (PubMed, J Alzheimers Dis) - "Cognitive function remained stable. These preliminary observations suggest that switching between anti-amyloid therapies may be safe in the short term, though larger prospective studies are warranted."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia

Efficacy and APOE ε4-stratified risk of donanemab in Alzheimer's disease: A systematic review and meta-analysis of randomized clinical trials. (PubMed, J Alzheimers Dis) - "Infusion reactions (RR, 11.90) and discontinuations (RR, 3.22) were also more frequent.ConclusionsDonanemab demonstrated modest cognitive benefits, the clinical significance of which remains uncertain. Independent, longer-term trials with rigorous methodology and active comparators are warranted to more clearly define its therapeutic value in the treatment of AD."

Clinical • Journal • Retrospective data • Review • Alzheimer's Disease • CNS Disorders • APOE

Donanemab exposure-response in early symptomatic Alzheimer's disease. (PubMed, Alzheimers Dement) - P1, P2, P3 | "Weight-based and flat dosing had similar exposure metrics; flat dosing was adopted. Donanemab exposure was influenced by weight and titer (not clinically relevant). 2.8 Centiloids/year amyloid reaccumulation rate observed upon donanemab treatment completion. Around 30% reduction in disease progression rate on treatment for integrated Alzheimer's Disease Rating Scale (iADRS) and Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB)."

Clinical • Journal • Alzheimer's Disease • CNS Disorders • Dementia

Recent Advances in Antibody Therapy for Alzheimer's Disease: Focus on Bispecific Antibodies. (PubMed, Int J Mol Sci) - "The regulatory approval of three anti-amyloid monoclonal antibodies (mAbs), including aducanumab, lecanemab, and donanemab, has established immunotherapy as a therapeutic approach to modify disease progression. This review combines existing information about antibody-based therapy in AD by focusing on bispecific antibody formats and their preclinical and clinical development, as well as biomarker-based patient selection and upcoming combination strategies. The combination of rationally designed bispecific antibodies with fluid and imaging biomarkers could show potential for overcoming existing therapeutic challenges and delivering significant clinical advantages."

IO biomarker • Journal • Review • Alzheimer's Disease • CNS Disorders • Inflammation

Comment by European Alzheimer's Disease Consortium (EADC) investigators on the negative recommendation of the CHMP on the marketing authorization of donanemab for early Alzheimer' s disease. (PubMed, J Prev Alzheimers Dis) - No abstract available

Journal • Alzheimer's Disease • CNS Disorders

Alzheimer's disease basics: we all should know. (PubMed, Neurol Res) - "Additionally, recent clinical trial data of anti-Aβ monoclonal antibodies (aducanumab, lecanemab, donanemab) were reviewed, with comparative analysis of efficacy, safety, and trial outcomes. While mAb therapies mark progress in disease modification, their success depends on patient stratification, early intervention, and safety profiling. Future directions must emphasize combinatorial and personalized approaches incorporating early biomarkers, neuroimaging, and emerging technologies to effectively combat the rising global burden of AD."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Inflammation • APOE • MAPT

FDA approves updated label for Lilly's Kisunla (donanemab-azbt) with new dosing in early symptomatic Alzheimer's disease (Eli Lilly Press Release) - "Eli Lilly and Company...announced today that the U.S. Food and Drug Administration (FDA) has approved a label update with a new recommended titration dosing schedule for Kisunla (donanemab-azbt), Lilly's once-monthly amyloid-targeting therapy for adults with early symptomatic Alzheimer's disease (AD), which includes people with mild cognitive impairment (MCI) as well as people in the mild dementia stage of AD, with confirmed amyloid pathology. In the TRAILBLAZER-ALZ 6 study, the modified titration schedule significantly lowered the incidence of amyloid-related imaging abnormalities with edema/effusion (ARIA-E) versus the original dosing schedule at 24 and 52 weeks, while still achieving similar levels of amyloid plaque removal and P-tau217 reduction."

FDA approval • Alzheimer's Disease

A Systematic Review of the Efficacy and Safety of Anti-amyloid Monoclonal Antibodies in Alzheimer's Disease. (PubMed, Cureus) - "Aducanumab showed dose-dependent effects on plaque clearance but had inconsistent cognitive outcomes and higher ARIA rates. Recent mAb trials provide promising evidence for disease modification in early AD stages, particularly with lecanemab and donanemab. However, variability in cognitive outcomes and safety concerns warrant cautious interpretation and long-term validation."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia

Current clinical trends in developing strategies for dementia disorders and the role of Korean Red Ginseng. (PubMed, J Ginseng Res) - "Recently, the development of the FDA approved monoclonal antibodies (mAbs) targeting amyloid proteins, such as aducanumab, lecanemab, and donanemab, etc. Although these are in initial stage, developing mAbs is believed to proposed as next stage of AD therapeutics. Additionally, pleiotropic phenomena of KRG, not only cognition but also overall human health systems, warranting further underling medical evidence. These efficacies and multi-effectiveness can be a high potential candidate for the current trends in developing strategies for dementia disorders."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia

The effect of modified donanemab titration on amyloid-related imaging abnormalities with edema/effusions and amyloid reduction: 18-month results from TRAILBLAZER-ALZ 6. (PubMed, J Prev Alzheimers Dis) - P3 | "A more gradual titration of donanemab dosing significantly reduced ARIA-E risk versus standard dosing. CLINICALTRIALS.GOV: NCT05738486."

Journal • Alzheimer's Disease • CNS Disorders

Is US residence a risk factor for Alzheimer's disease? (PubMed, J Alzheimers Dis) - "It is around 0.7% in the UK, 0.9% in Denmark, and worldwide the estimate is 0.5%. Alongside risk factor reduction, the Centers for Medicare and Medicaid Services could strengthen the US fight against AD by reconsidering its October 2023 decision to liberalize reimbursement of amyloid PET scans, or better yet, advise replacing these non-specific scans with FDG-PET, which shows what AD is really about: impaired regional brain function."

Journal • Alzheimer's Disease • CNS Disorders

Closed-form confidence intervals for saved time using summary statistics in Alzheimer's disease studies. (PubMed, Stat Methods Med Res) - "We compare them with regard to coverage probability and interval width under various disease progression patterns that are commonly observed in AD symptomatic therapy and disease-modifying therapy trials. Data from the phase 3 donanemab trials are used to illustrate the application of the new CI methods."

Journal • Alzheimer's Disease • CNS Disorders

A blood test for Alzheimer's disease. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Alzheimer's Disease • CNS Disorders

Management of Patients With Mild Cognitive Impairment in the Era of Anti-Amyloid Therapy: A Worldwide Neurology Survey. (PubMed, Neurol Clin Pract) - "We performed a worldwide electronic survey of neurology practitioners through the Practice Current section of Neurology® Clinical Practice with clinical and practice-related questions in November 2019-August 2021 and repeated it in May-October 2023 after the FDA's approval of aducanumab and lecanemab but before the approval of donanemab. Our results highlight practice differences among cognitive subspecialists and other practitioners worldwide in the management of MCI. Attitudes toward anti-amyloid therapy indicate cautious optimism, with concerns about side effects but a general interest to prescribe."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia

Imaging of Healthy Subjects using [11C]COU: Dosimetry, Metabolite Analysis, and Kinetics (SNMMI 2025) - "Recently, 2 anti-amyloid drugs have been approved by FDA for treatment of ADRD, lecanemab and donanemab. No adverse events were reported from any healthy subjects that participated in this study. The trapping rate of this tracer is extremely fast. This caused the estimates of the individual rate parameters k2 and k3 to be highly correlated and highly variable."

Clinical

Imaging of Healthy Subjects using [11C]COU: Dosimetry, Metabolite Analysis, and Kinetics (SNMMI 2025) - "Recently, 2 anti-amyloid drugs have been approved by FDA for treatment of ADRD, lecanemab and donanemab. No adverse events were reported from any healthy subjects that participated in this study. The trapping rate of this tracer is extremely fast. This caused the estimates of the individual rate parameters k2 and k3 to be highly correlated and highly variable."

Clinical