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

Anti-amyloid antibody equilibrium binding to Aβ aggregates from human Alzheimer disease brain. (PubMed, bioRxiv) - "Equilibrium binding constants (K D ) and total Aβ binding (B max ) of recombinant aducanumab, lecanemab, and donanemab equivalents to human brain soluble and insoluble amyloid plaque-enriched and CAA-enriched Aβ aggregates. The APOE ε4 allele may plausibly increase ARIA-E risk by making antibody-accessible Aβ more soluble. These results have implications for improving the safety and efficacy of current and future anti-amyloid antibody therapies."

IO biomarker • Journal • Alzheimer's Disease • CNS Disorders • APOE

Comparisons of efficacy and safety of immunotherapies for Alzheimer's disease treatment: a network meta-analysis of randomized controlled trials. (PubMed, Clin Med (Lond)) - "Anti-Aβ mAbs, particularly donanemab and lecanemab, demonstrated superior efficacy over other immunotherapies in slowing cognitive deterioration, supporting their role in AD management."

Journal • Retrospective data • Review • Alzheimer's Disease • CNS Disorders • Dementia

MRI protocols and sequences for amyloid-related imaging abnormalities monitoring in Alzheimer's disease patients treated with monoclonal antibodies. (PubMed, Curr Opin Neurol) - "ARIA reflect vascular vulnerability during amyloid clearance in AD. Their management requires close collaboration between neurologists and neuroradiologists, with harmonized MRI protocols and risk mitigation strategies critical for safe and effective use of disease-modifying therapies."

Journal • Alzheimer's Disease • CNS Disorders • Hematological Disorders • APOE

Therapeutic time window of disease-modifying therapy for early Alzheimer's disease. (PubMed, Alzheimers Dement (N Y)) - "Recently approved disease-modifying therapies (DMT) for early Alzheimer's disease (AD), including lecanemab and donanemab, require patients to meet specific eligibility criteria for treatment. These findings will support more proactive patient management, ensuring timely evaluations and prioritization of patients at higher risk of ineligibility, particularly where DMT access is limited. We examined the "therapeutic time window" eligibility for disease-modifying therapy.Longitudinal data from National Alzheimer's Coordinating Center (NACC) and Alzheimer's Disease Neuroimaging Initiative (ADNI) were used to quantify eligibility duration.Higher Clinical Dementia Rating-Global Score (CDR-GS) or lower Mini-Mental State Examination (MMSE) at baseline were associated with shorter window length.Our results will help optimize the management of the wait time for disease-modifying therapies (DMT) treatment."

Journal • Alzheimer's Disease • CNS Disorders • Dementia

A Study of Donanemab, RG6289, or the Combination of Donanemab and RG6289 in Presenilin 1 (PSEN1) E280A Mutation Carriers for the Treatment of Autosomal-Dominant Alzheimer's Disease (clinicaltrials.gov) - P2/3 | N=240 | Not yet recruiting | Sponsor: Banner Health

New P2/3 trial • Alzheimer's Disease • CNS Disorders

Chimeric antigen receptors discriminate between tau and distinct amyloid-beta species. (PubMed, J Transl Med) - "Our findings demonstrate that CARs can detect and discriminate between tau PFFs, Aβ1-42, and Aβp3-42 aggregates. This highlights the potential of repurposing AD antibodies for CAR-based therapies to selectively target tau NFTs and distinct forms of Aβ senile plaques."

IO biomarker • Journal • Alzheimer's Disease • CNS Disorders • Oncology • CD4 • CD69 • IL2RA

A 2025 update on treatment strategies for the Alzheimer's disease spectrum. (PubMed, J Chin Med Assoc) - "The advent of anti-amyloid immunotherapy, including FDA-approved monoclonal antibodies such as lecanemab and donanemab, has proven efficacy in slowing cognitive decline in early-stage AD...Cholinesterase inhibitors and memantine remain the standard treatments for mild, moderate to severe dementia, providing symptomatic relief and functional stabilization...A proactive approach, combining early detection with disease-modifying and symptomatic therapies, is essential for improving patient outcomes and quality of life. This article synthesizes current knowledge and provides a roadmap for clinicians and researchers navigating the evolving landscape of AD treatment."

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

Evaluating the Cost-Effectiveness of Pharmacological Therapy in Alzheimer Disease in Brazil. (PubMed, Value Health Reg Issues) - "The SoC is a cost-effective pharmacological intervention for AD, offering the lowest cost per QALY gains over a 20-year period."

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

Prospects for treating Alzheimer's disease (PubMed, Zh Nevrol Psikhiatr Im S S Korsakova) - "Currently, the treatment of Alzheimer's disease (AD) is limited to symptomatic therapy with acetylcholinesterase inhibitors and memantine, which contribute to a temporary improvement in cognitive functions and increased independence in everyday life but have little effect on the progression rate of the neurodegenerative process...Anti-amyloid therapies such as aducanumab, lecanumab, and donanemab have recently been officially approved for practical use in some countries around the world. Therapeutic strategies for tau protein-related disorders, neuroinflammation, insulin resistance, and other neurodegeneration mechanisms are also being actively studied. Along with drug therapy, noninvasive brain stimulation methods such as transcranial magnetic stimulation and transcranial electrical stimulation, which have a high safety profile and proven effectiveness, are actively developing."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Developmental Disorders • Gene Therapies • Inflammation • Metabolic Disorders

Psychopharmacological Advances in the Management of Alzheimer's Disease (APA 2025) - "Following an introduction that will define the scope of the problem in managing patients with AD, the session will then provide a quick overview of the current evidence supporting use of symptomatic treatments including cholinesterase inhibitors and memantine in the management of the cognitive symptoms of Alzheimer's disease...Two agents, lecanemab and donanemab, are approved by the FDA for use in mild stages of the disease...Clinical cases will then be used to update attendees regarding recent advances in the psychopharmacological treatment of select neuropsychiatric symptoms in AD dementia, specifically the treatment of agitation with brexpiprazole, apathy with methylphenidate, and insomnia with the dual orexin receptor antagonists (DORA)...Objective Three: The participant will be able to identify the use of the new CPT code that allows clinicians to provide counseling to family caregivers regarding the management of agi Objective Four: The participant will be able..."

Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Insomnia • Psychiatry • Sleep Disorder

Anti-amyloid immunotherapies for Alzheimer's disease: Administration, side effects, and overall framework. (PubMed, Geriatr Nurs) - "Recently, the Food and Drug Administration (FDA) approved the use of aducanumab (Aduhelm), lecanemab (Leqembi), and donanemab (Kisunla) in patients with mild cognitive impairment (MCI) and early-stage dementia secondary to Alzheimer's disease (AD). Given the novelty of these medications, limited educational resources are available to front line medical staff, primarily nurses, who are involved with patient education, administration of medications, and monitoring for side effects. The aim of this manuscript is to discuss the mechanism of action, indications, administration, and side effects associated with anti-amyloid immunotherapies and to provide medical staff with an assessment and educational framework to use in their practice."

Adverse events • Journal • Alzheimer's Disease • Cerebral Hemorrhage • CNS Disorders • Cognitive Disorders • Dementia • Hematological Disorders

The Unseen Progress: How PROs May Overlook the Value of Slowing Degenerative Decline (ISPOR 2025) - " The pivotal trials of recent Food and Drug Administration (FDA)-approved treatments for degenerative diseases were analyzed; these included nintedanib for idiopathic pulmonary fibrosis (IPF), tofersen for amyotrophic lateral sclerosis (ALS), ocrelizumab for primary-progressive multiple sclerosis (PPMS), and donanemab-azbt for Alzheimer’s disease (AD). PROs may not detect the benefit of treatment for degenerative diseases. A potential explanation is misalignment in patient expectations. Future research is needed to evaluate how treatment benefits can be appropriately captured by patient experience data."

Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Idiopathic Pulmonary Fibrosis • Immunology • Multiple Sclerosis • Pulmonary Disease • Respiratory Diseases

Monoclonal antibodies against beta-amyloid protein (lecanemab and donanemab) should not be used in the treatment of Alzheimer's disease. (PubMed, Arq Neuropsiquiatr) - "Besides, the incidence of adverse events is high and potentially severe. Although there are reasons to celebrate this first step towards disease-modifying therapies for AD, lecanemab and donanemab should not be used to treat AD in clinical pratice."

Journal • Alzheimer's Disease • CNS Disorders

Adverse Events Associated With Recently Approved Alzheimer's Drugs: A Real-World Pharmacovigilance Study (ISPOR 2025) - "Aducanumab, lecanemab, and donanemab were recently approved therapies targeting beta-amyloid removal in the brain. FDAERs provide a rapid understanding of Real-world safety signals for AD therapies which demonstrated similar overall organ-level adverse effects, however distinct differences in specific events were noted."

Adverse events • Clinical • Real-world • Real-world evidence • Alzheimer's Disease • Cerebral Hemorrhage • CNS Disorders • Fatigue • Hematological Disorders • Pain

Cost-Effectiveness of Delaying Progression of Alzheimer's Disease with Novel Monoclonal Antibodies: A Societal Perspective (ISPOR 2025) - "This research aims to estimate the cost impact and cost-effectiveness of Aducanumab, Donanemab, and Lecanemab in delaying progression in early AD patients. New monoclonal AD treatments were estimated to add substantial costs with modest clinical benefits, with Donanemab adding the highest cost. The cost-effectiveness of the agents is substantially influenced by the patient’s age at treatment initiation, treatment efficacy in slowing disease progression, and the cost of medications."

Cost effectiveness • HEOR • Alzheimer's Disease • CNS Disorders

Alzheimer's Is a Multiform Disease of Sustained Neuronal Integrated Stress Response Driven by the C99 Fragment Generated Independently of AβPP; Proteolytic Production of Aβ Is Suppressed in AD-Affected Neurons: Evolution of a Theory. (PubMed, Int J Mol Sci) - "There is, however, a proverbial snowball's chance in hell of them being effective in symptomatic AD, lecanemab, donanemab, and any other "…mab" or "…stat" notwithstanding. If properly executed, these RNA-based strategies would not interfere with the protein-coding potential of AβPP mRNA, and each would be capable of both preventing and stopping the AβPP-independent generation of C99 and thus of either preventing AD or arresting the progression of the disease in its conventional and unconventional forms. The paper is interspersed with "validation" sections: every conceptually significant notion is either validated by the existing data or an experimental procedure validating it is proposed."

Journal • Review • Alzheimer's Disease • CNS Disorders • Infectious Disease • Inflammation • Mood Disorders • Targeted Protein Degradation

Clinical evaluation of medicines for patients with mild cognitive impairment and mild dementia due to Alzheimer's disease in Japan. (PubMed, Alzheimers Dement (N Y)) - "For regulatory approval, future drugs will be required to demonstrate a benefit-risk balance equivalent to or more favorable than that of the approved anti-Aβ antibody drugs. Lecanemab and donanemab were approved in Japan for early Alzheimer's disease in 2023 and 2024, respectively.Drug efficacy was considered clinically meaningful after comprehensive evaluation.Biomarker evaluation, including amyloid beta (Aβ), is crucial to support the intended mechanism of action.Aβ reduction did not correlate with the suppression of clinical symptom progression in individual cases.No biomarker is validated as a surrogate, and minimal clinically important difference cannot be inferred from Aβ reduction."

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

Lilly's Kisunla (donanemab) receives marketing authorization in Australia for the treatment of early symptomatic Alzheimer's disease (PRNewswire) - "Eli Lilly and Company...announced today that the Australian Therapeutic Goods Administration (TGA) has granted marketing authorization for Kisunla (donanemab), an injection for intravenous infusion every four weeks to treat mild cognitive impairment and mild dementia due to Alzheimer's disease in adults who are Apolipoprotein E ε4 (ApoE ε4) heterozygotes or non-carriers. Kisunla is the first amyloid-targeting therapy for people with Alzheimer's registered in Australia and the only amyloid plaque-targeting therapy with evidence to support stopping therapy when amyloid plaques are removed....The registration of Kisunla in Australia was based on the TRAILBLAZER-ALZ 2 Phase 3 and TRAILBLAZER-ALZ 6 clinical trial data."

Approval • Alzheimer's Disease • Dementia

Safety, Tolerability, and Pharmacokinetics of Donanemab in Healthy Chinese Participants: A Phase 1, Randomized, Double-Blind, Placebo-Controlled Study. (PubMed, Clin Pharmacol Drug Dev) - "All donanemab recipients developed treatment-emergent antidrug antibodies (ADAs) in the inpatient and follow-up periods, with similar ADA titer ranges across all donanemab doses. Single IV doses of donanemab 350, 700, and 1400 mg showed acceptable safety, tolerability, and dose-proportional PK in healthy Chinese adults."

Clinical • Journal • P1 data • PK/PD data • Alzheimer's Disease • CNS Disorders • Dementia

Eli Lilly sees Alzheimer's drug development beyond amyloid beta targeting (MSN News) - "Steele noted that the company is also looking at the possibility Kisunla could be used as a treatment for earlier stages of Alzheimer's, citing the TRAILBLAZER ALZ-3 trial which is focused on patients that have amyloid plaque but no disease symptoms. A data readout is expected in 2027."

P3 data • Alzheimer's Disease

Amyloid immunotherapy for Alzheimer's disease: the case for cautious adoption. (PubMed, Arq Neuropsiquiatr) - "The licensing of lecanemab and donanemab, disease-modifying immunotherapies for Alzheimer's disease (AD) targeting β-amyloid pathology, has been met with difference in opinion about efficacy, adverse effects, and cost-effectiveness. Here we summarize the current situation and make the case for cautious adoption of these treatments into clinical practice. This opinion is predicated on four main observations: 1) these treatments impact the core pathologies of AD and result in meaningful benefits; 2) while adverse effects can be serious, these are proving manageable in clinical practice; 3) upscaling services to deliver these agents is likely to provide wider benefits for diagnosing and treating dementia and facilitating the adoption of future treatments from the dementia drug pipeline; and 4) factoring in both the wider societal cost of care and potential for continued accrual of long term benefits will be likely to bring these treatments within acceptable..."

Journal • Alzheimer's Disease • CNS Disorders • Dementia

TRAILBLAZER-ALZ 4: A phase 3 trial comparing donanemab with aducanumab on amyloid plaque clearance in early, symptomatic Alzheimer's disease. (PubMed, Alzheimers Dement) - P3 | "Donanemab treatment resulted in earlier and greater AP clearance compared to aducanumab. ARIA frequencies were consistent with prior studies."

Clinical • Journal • P3 data • Alzheimer's Disease • CNS Disorders

The Efficacy of Anti-amyloid Monoclonal Antibodies in Early Alzheimer's Dementia: A Systematic Review. (PubMed, Ann Indian Acad Neurol) - "Our findings highlight the need to consider the complex pathophysiology of AD in treatment development. Focusing solely on the amyloid-beta hypothesis may be inadequate; further research is necessary to understand the underlying mechanisms and develop treatments for the multifactorial nature of the disease."

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

Two new drugs against Alzheimer’s open horizon of hope for 10,000 patients in Malaga province (SUR in English) - "The two drugs - lecanemab and donanemab, - which prolong life by three to five years if applied in the early stages, are expected to arrive in Spain"

Launch Europe • Alzheimer's Disease

Coverage Gaps: Do U.S. Commercial Health Plans Have Concordant Alzheimer's Disease Therapy & Testing Policies? (ISPOR 2025) - "These policies were effective from 1/1/2024 through 12/31/2024 and included FDA-approved therapies (lecanemab and donanemab) and testing for amyloid pathology (cerebrospinal fluid [CSF] biomarker assays and amyloid positron emission tomography [PET] scans). Although there's often alignment between amyloid targeting therapies and testing policies, inconsistencies remain. As new technologies like plasma-based biomarkers become available, it’s essential for health plans to ensure policy concordance to minimize access variability for AD patients."

Discordant • HEOR • Alzheimer's Disease • CNS Disorders