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

Evaluating Donanemab: Advances and Challenges in Alzheimer Disease Treatment. (PubMed, Am J Ther) - No abstract available

Journal • Alzheimer's Disease • CNS Disorders

Comparison of the efficacy of updated drugs for the treatment on the improvement of cognitive function in patients with Alzheimer 's disease: A systematic review and network meta- analysis. (PubMed, Neuroscience) - "Donanemab and Lecanemab showed good efficacy in ADCS-ADL and CDR-SB, respectively. GV-971 is the best choice to improve ADAS cogs and NPI."

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

Passive anti-amyloid β immunotherapy in Alzheimer's disease-opportunities and challenges. (PubMed, Lancet) - "We discuss clinical trial results of aducanumab, lecanemab, and donanemab. In our view, we are experiencing a fundamental shift from syndrome-based Alzheimer's dementia care to early, biomarker-guided treatment of Alzheimer's disease. This shift requires substantial adjustments of infrastructure and resources, but also holds promise of eventually achieving substantial slowing of disease progression and delaying dementia."

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

Revolutionizing Alzheimer's Diagnosis and Management: The Dawn of Biomarker-Based Precision Medicine. (PubMed, Dement Neurocogn Disord) - "The treatment landscape is shifting toward personalized medicine, highlighted by advancements in Aβ immunotherapies, such as lecanemab and donanemab. The integration of fluid biomarkers into clinical practice represents a significant advance in AD management, providing the potential for early and precise diagnosis, coupled with personalized therapeutic approaches. This heralds a new era in combating this debilitating disease."

Biomarker • IO biomarker • Journal • Review • Alzheimer's Disease • CNS Disorders • Dementia • NEFL

Use of anti-amyloid therapies for Alzheimer's disease in Brazil: a position paper from the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology. (PubMed, Dement Neuropsychol) - "Novel therapies for Alzheimer's disease, particularly anti-amyloid drugs like lecanemab and donanemab, have shown modest clinical benefits but also significant risks. Recommendations include careful patient selection, risk-benefit analysis, and the importance of proven amyloid pathology for treatment. Future work involves further research on anti-amyloid therapies in Brazil and the development of more effective treatments for Alzheimer's disease."

Journal • Alzheimer's Disease • CNS Disorders

Critical assessment of anti-amyloid-β monoclonal antibodies effects in Alzheimer's disease: a systematic review and meta-analysis highlighting target engagement and clinical meaningfulness. (PubMed, Sci Rep) - "In subgroup analyses by individual drug, Donanemab and Lecanemab induced the largest benefits. PROSPERO registration no. CRD42022381334."

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

Lilly’s Kisunla does not demonstrate ’good value’ for UK’s NHS (Yahoo Finance) - "Eli Lilly’s Kisunla (donanemab) will not yet be made available to Alzheimer’s patients in the UK after the National Institute for Health and Care Excellence (NICE) said it doesn’t demonstrate good value for UK's NHS...NICE, which acts as the UK’s price watchdog, said that although the monthly injection slows disease progression by four to seven months, as demonstrated in the Phase III TRAILBLAZER-ALZ 2 (NCT04437511) study, there are 'significant uncertainties about how much benefit donanemab provides, and how long this lasts for after stopping treatment'. It also said that more evidence is needed on the clinical and cost-effectiveness of Kisunla."

NICE • Alzheimer's Disease • CNS Disorders

ABTrans: A Transformer-based Model for Predicting Interaction between Anti-Aβ Antibodies and Peptides. (PubMed, Interdiscip Sci) - "Using ABTrans, we examined the cross-reaction of anti-Aβ antibodies with other human amyloidogenic proteins, revealing that Aducanumab and Donanemab exhibited the least cross-reactivity. Additionally, we systematically screened interactions between eleven selected anti-Aβ antibodies and all human proteins to identify potential off-target candidates."

Journal • Alzheimer's Disease • CNS Disorders

Differential Health-Economic Outcomes of Anti-Amyloid Treatment for Alzheimer's Disease Between Ethnoracial Groups in the United States (ISPOR-EU 2024) - " We used a previously validated mathematical model of Alzheimer’s disease treatment to project health and economic outcomes under usual care vs. with donanemab (an exemplar anti-amyloid antibody) for three ethnoracial groups: Hispanic, non-Hispanic Black, and non-Hispanic White... Based on current ethnoracial disparities in AD care, the benefits and costs of anti-amyloid treatment are likely to be unevenly distributed between ethnoracial groups, with Black individuals receiving a markedly lower share of the benefits. Efforts to improve timely diagnosis rates for Black patients would facilitate a more equitable distribution of benefits."

HEOR • Alzheimer's Disease • CNS Disorders

Modified Titration of Donanemab Demonstrated Reduction of ARIA-E in Early Symptomatic Alzheimer's Disease Patients in Phase 3b study (PRNewswire) - P3b | N=800 | TRAILBLAZER-ALZ 6 (NCT05738486) | Sponsor: Eli Lilly and Company | "Eli Lilly and Company...today announced positive results from the TRAILBLAZER-ALZ 6 Phase 3b study, showing a reduction in amyloid-related imaging abnormalities with edema/effusion (ARIA-E) at the 24-week primary endpoint for people receiving a slightly modified titration of donanemab in adults with early symptomatic Alzheimer's disease (AD)....The only difference between the modified titration and the standard dosing regimen is the shift of one vial from the first infusion to the third infusion. Pharmacokinetic (PK) analysis demonstrated equivalent cumulative exposure between modified titration and standard dosing regimen."

P3 data • Alzheimer's Disease • CNS Disorders

A Real-World Comparative Study of Donanemab (LY3002813) Plus Usual Care Versus Usual Care Alone in US Participants With Early Symptomatic Alzheimer's Disease (clinicaltrials.gov) - P=N/A | N=3060 | Recruiting | Sponsor: Eli Lilly and Company | Not yet recruiting ➔ Recruiting

Enrollment open • HEOR • Real-world • Real-world evidence • Alzheimer's Disease • CNS Disorders

Chemical-Driven Amyloid Clearance for Therapeutics and Diagnostics of Alzheimer's Disease. (PubMed, Acc Chem Res) - "However, recent approvals of anti-Aβ antibody drugs by the FDA, including aducanumab (Aduhelm), lecanemab (Leqembi), and donanemab (Kisunla), have prompted a re-evaluation of this perspective. In clinical practice, we anticipate that these findings will contribute to the development of patient-friendly therapeutic and diagnostic interventions, including self-administered and orally available options, thereby enhancing disease management and overall quality of life for individuals with AD. Furthermore, this research extends beyond AD, potentially offering insights into other neurodegenerative diseases characterized by protein aggregation."

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

NICE rejects Alzheimer's drug donanemab owing to cost and "significant health risks". (PubMed, BMJ) - No abstract available

Journal • NICE • Alzheimer's Disease • CNS Disorders

Lilly's Kisunla (donanemab-azbt) Receives Marketing Authorization in Great Britain for the Treatment of Mild Cognitive Impairment and Mild Dementia Due to Alzheimer's Disease in Adult Patients Who Are Apolipoprotein E Ε4 Heterozygotes or Non-Carriers (Eli Lilly Press Release) - "Eli Lilly and Company...announced today that the Medicines and Healthcare products Regulatory Agency (MHRA) has granted marketing authorization for donanemab, an injection for intravenous infusion every four weeks to treat mild cognitive impairment and mild dementia due to Alzheimer's disease in eligible adults in Great Britain. Eligible patients are limited to apolipoprotein E ε4 (ApoE ε4) heterozygotes or non-carriers, which is a requirement for the class of currently approved amyloid-targeting therapies in Great Britain....'Donanemab demonstrated meaningful results for people with early symptomatic Alzheimer's disease by significantly slowing cognitive and functional decline in our TRAILBLAZER-ALZ 2 study'."

MHRA approval • Alzheimer's Disease • Dementia

Anti-amyloid β Antibody Therapies for Alzheimer's Disease: Association between the Target of Amyloid β Aggregates and the Clinical Efficacy of Anti-amyloid β Antibody. (PubMed, Intern Med) - "Phase 3 clinical trials have validated the clinical efficacy of some anti-amyloid β (Aβ) antibody therapies, such as lecanemab and donanemab...Solanezumab and bapinezumab target Aβ aggregates of monomers alone or from monomers to low molecular weight oligomers. Anti-Aβ antibody therapies with clinical cognitive efficacy are thus characterized by targeting large-molecular-weight Aβ aggregates, such as protofibrils and plaques. In addition, a positive association was observed between the reduction in amyloid deposition and the inhibition of cognitive decline."

Journal • Alzheimer's Disease • CNS Disorders

The Effect of Different Donanemab Dosing Regimens on ARIA-E and Amyloid Lowering in Adults with Early Symptomatic Alzheimer's Disease: Primary Outcome Results from TRAILBLAZER-ALZ 6 (CTAD 2024) - No abstract available

Clinical • Alzheimer's Disease • CNS Disorders

Amyloid-Directed Antibodies: Past, Present, and Future. (PubMed, J Alzheimers Dis) - "Specifically, lecanemab and donanemab will require further clinical studies to optimize patient selection based on safety profiles. Despite some key limitations, these two drugs are paving the way for disease-modifying treatments in patients displaying early signs of amyloid pathology."

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

Novel regional flortaucipir visual read approaches to stratify subjects by tau spread: Evaluation in TRAILBLAZER-ALZ 2 phase 3 study of donanemab (CTAD 2024) - No abstract available

Clinical • P3 data

Disease-Modifying Therapies of Alzheimer’s Disease (Neuroscience 2024) - "The recent emergence of disease-modifying therapies (DMT) targeting amyloid ß (Aß) in early Alzheimer’s disease (AD), e.g. lecanemab and donanemab, opened up a new era for AD therapies. Secondary prevention trials in amyloid-positive asymptomatic elderly individuals are currently underway. These clinical activities will pave the way toward the development of AD therapies targeting its very early stages."

Alzheimer's Disease • CNS Disorders

LEC08. Special Lecture: Disease-Modifying Therapies of Alzheimer’s Disease — Takeshi Iwatsubo (Neuroscience 2024) - "DESCRIPTION The recent emergence of disease-modifying therapies (DMT) targeting amyloid ß (Aß) in early Alzheimer’s disease (AD), e.g. lecanemab and donanemab, opened up a new era for AD therapies. These clinical activities will pave the way toward the development of AD therapies targeting its very early stages. To submit a question during the session, use the annual meeting mobile app."

Alzheimer's Disease • CNS Disorders

Donanemab: Appropriate Use Recommendations (CTAD 2024) - No abstract available

Late-breaking abstract

Screening and baseline results from the donanemab preclinical Alzheimer's disease TRAILBLAZER-ALZ 3 study (CTAD 2024) - No abstract available

Preclinical • Alzheimer's Disease • CNS Disorders

Moderator (Neuroscience 2024) - "The recent emergence of disease-modifying therapies (DMT) targeting amyloid ß (Aß) in early Alzheimer’s disease (AD), e.g. lecanemab and donanemab, opened up a new era for AD therapies. Secondary prevention trials in amyloid-positive asymptomatic elderly individuals are currently underway. These clinical activities will pave the way toward the development of AD therapies targeting its very early stages."

Alzheimer's Disease • CNS Disorders

Anti-Amyloid Antibody Therapy for Alzheimer's Disease (PubMed, Brain Nerve) - "Among the many recent phase 3 clinical trials that have investigated the role of anti-Aβ antibodies in AD, some have shown the clinical efficacy of aducanumab, lecanemab, and donanemab in these patients. Lecanemab showed selectivity towards protofibrils over fibrils, and donanemab was specifically directed against Aβ only in brain-specific amyloid plaques. In contrast, other anti-Aβ antibodies did not show efficacy in AD."

Journal • Review • Alzheimer's Disease • CNS Disorders

The basis of anti-Aβ antibody therapy: The toxicity of Aβ aggregates and the mechanism of action of anti-Aβ antibodies. (PubMed, Intern Med) - "Using high-speed atomic force microscopy, we have previously reported that lecanemab, which has a high affinity for protofibrils, binds to and surrounds them. Donanemab, a recombinant monoclonal antibody that primarily targets fibrils composed of N3pG Aβ, has also attracted attention because of its efficacy in phase 3 clinical trials in patients with early stage AD."

Journal • Alzheimer's Disease • CNS Disorders