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

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

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

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

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

A Study of LY3002813 in Participants With Alzheimer's Disease (clinicaltrials.gov) - P1 | N=63 | Completed | Sponsor: Eli Lilly and Company | N=100 ➔ 63

Enrollment change • Alzheimer's Disease • CNS Disorders • Cognitive Disorders

Single domain antibody-scFv conjugate targeting amyloid β and TfR penetrates the blood-brain barrier and interacts with amyloid β. (PubMed, MAbs) - "Immunotherapies, including the marketed antibodies lecanemab (Leqembi®) and donanemab (KisunlaTM), offer promise but face hurdles due to limited delivery across the blood-brain barrier (BBB). Our findings suggest that these novel VHH-based FPs hold potential for therapeutic and diagnostic applications in AD, providing a strategy to overcome BBB limitations and enhance brain targeting of antibody-based treatments. Furthermore, our results suggest that a given bispecific TfR-binding fusion format has a window of "optimal" affinity where parenchymal delivery is adequate, while blood pharmacokinetics aligns with the desired application of the fusion protein."

Journal • Alzheimer's Disease • CNS Disorders

Can Targeted Protein Degradation Technology Provide a Potential Breakthrough in the Development of Anti-AD Drugs? (PubMed, ACS Chem Neurosci) - "Recent advancements in Alzheimer's disease (AD) research have led to the approval of lecanemab and donanemab, highlighting the effectiveness of amyloid-beta (Aβ) degradation as a treatment for AD. The prospect of small molecule Aβ degraders as a potential treatment, which utilizes emerging targeted protein degradation technology, is exciting, given their ability to address some of the limitations of current therapies and their promising future in AD treatment. Despite facing challenges, these degraders are poised to become a future treatment option, harnessing scientific breakthroughs for more targeted and effective AD therapy."

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

Metabolic resistance of Aβ3pE-42, a target epitope of the anti-Alzheimer therapeutic antibody, donanemab. (PubMed, Life Sci Alliance) - "Here, we present experimental evidence that accounts for the aging-associated Aβ3pE-42 deposition: Aβ3pE-42 was metabolically more stable than other Aβx-42 variants; deficiency of neprilysin, the major Aβ-degrading enzyme, induced a relatively selective deposition of Aβ3pE-42 in both APP transgenic and App knock-in mouse brains; Aβ3pE-42 deposition always colocalized with Pittsburgh compound B-positive cored plaques in APP transgenic mouse brains; and under aberrant conditions, such as a significant reduction in neprilysin activity, aminopeptidases, dipeptidyl peptidases, and glutaminyl-peptide cyclotransferase-like were up-regulated in the progression of aging, and a proportion of Aβ1-42 may be processed to Aβ3pE-42. Our findings suggest that anti-Aβ therapies are more effective if given before Aβ3pE-42 deposition."

Journal • Alzheimer's Disease • CNS Disorders

What's in It for Me? Contextualizing the Potential Clinical Impacts of Lecanemab, Donanemab, and Other Anti-β-amyloid Monoclonal Antibodies in Early Alzheimer's Disease. (PubMed, eNeuro) - "A new era of disease-modifying therapy for Alzheimer's disease (AD) arrived in 2021 following the Food and Drug Administration's (FDA) decision to grant accelerated approval for aducanumab, an anti-β-amyloid (Aβ) monoclonal antibody designed to target Aβ aggregates, a biological component of AD. In the process of this exercise, we outline a generally useful concept termed Summative Treatment-Associated Benefit measuring Long-term Efficacy/Effectiveness Area as a metric of summative benefits of treatment over the life course of an individual. Second, we consider current real-world factors, such as conditions of FDA approval and other points involved in clinical decision-making that will influence and/or temper the actual impacts of this drug class."

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

Amyloid related imaging abnormalities in the emergency setting. (PubMed, Emerg Radiol) - "This report details the case of a 64-year-old woman undergoing donanemab treatment who developed severe ARIA, characterized by extensive vasogenic edema and multiple microhemorrhages. The increasing use of MABs necessitates heightened awareness and expertise among emergency radiologists to identify findings of ARIA effectively, ensuring timely and appropriate care for patients undergoing these novel therapies."

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

Donanemab: Conflicts of interest found in FDA committee that approved new Alzheimer's drug. (PubMed, BMJ) - No abstract available

FDA event • 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

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

Late-breaking abstract

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

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

Limitations and potential strategies of immune checkpoint blockade in age-related neurodegenerative disorders. (PubMed, J Physiol Sci) - "Lately, disease-modifying therapies (DMTs) that can alter the pathophysiology that underlies AD with anti-Aβ monoclonal antibodies (MAbs) (e.g., aducanumab, lecanemab, gantenerumab, donanemab, solanezumab, crenezumab, tilavonemab). Similarly, in Parkinson's disease (PD), DMTs utilizing anti-αSyn (MAbs) (e.g., prasinezumab, cinpanemab,) are progressively being developed and evaluated in clinical trials. These therapies are based on the hypothesis that both AD and PD may involve systemic impairments in cell-dependent clearance mechanisms of amyloid-beta (Aβ) and alpha-synuclein (αSyn), respectively, meaning the body's overall inability to effectively remove Aβ and αSyn due to malfunctioning cellular mechanisms. In this review we will provide possible evidence behind the use of immunotherapy with MAbs in AD and PD and highlight the recent clinical development landscape of anti-Aβ (MAbs) and anti-αSyn (MAbs) from these clinical trials in order to better investigate..."

Checkpoint block • Checkpoint inhibition • Journal • Review • Alzheimer's Disease • CNS Disorders • Dementia • Inflammation • Movement Disorders • Parkinson's Disease

Alzheimer's treatment – anti amyloid monoclonal antibodies: the role of the psychiatrist (ECNP 2024) - "Aducanumab [1], Lecanemab [2] and Donanemab [3] are three anti-amyloid monoclonal antibodies (MBAs) that act at different stages of the aggregation and accumulation of amyloid. These therapies provide modestly improved survival and have substantial toxicity. Whether a possible 30% reduction in disease progression is sufficiently desirable to accept the inconvenience and potential harm associated with anti-amyloid MAB therapy will be a challenging decision for most patients, care partners and assisting physicians."

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

Lilly's Kisunla (donanemab-azbt) Approved in Japan for the Treatment of Early Symptomatic Alzheimer's Disease (PRNewswire) - "The Ministry of Health, Labour and Welfare Japan has approved Kisunla (donanemab-azbt, 350 mg/20 mL every four weeks injection for IV infusion), Eli Lilly and Company's (NYSE: LLY) Alzheimer's treatment for adults with early symptomatic Alzheimer's disease (AD), which includes people with mild cognitive impairment (MCI) as well as people with the mild dementia stage of AD, with confirmed amyloid pathology....The application to the PMDA was based on the efficacy and safety data from TRAILBLAZER-ALZ 2 Phase 3 clinical study."

Japan approval • Alzheimer's Disease • CNS Disorders

AUPN Session: Navigating Neurotherapeutic Horizons: Managing the Practical Aspects of the Novel Alzheimer's Therapeutics* (ANA 2024) - "Description This session will describe the process of setting up an outpatient infusion program for the two new Alzheimer's biologicals Lecanemab and Donanemab. Explain common and serious adverse reactions and how to appropriately monitor. Discuss the process of working with insurance companies."

Alzheimer's Disease • CNS Disorders

Estimating the Economically Justifiable Price of Limited-Duration Treatment with Donanemab for Early Symptomatic Alzheimer's Disease in the United States. (PubMed, Neurol Ther) - P3 | "Results from this modeling simulation informed by the TRAILBLAZER-ALZ 2 study support an EJP for limited-duration treatment with donanemab that exceeds per-dose list prices for currently available amyloid-targeting therapies, implying potentially lower lifetime costs and better value for money."

Journal • Alzheimer's Disease • CNS Disorders

Anti-amyloid Antibody Drugs as Disease-Modifying Therapies for Alzheimer's Disease (PubMed, Brain Nerve) - "Notable drugs such as aducanumab, lecanemab, and donanemab have shown potential in clinical trials, leading to the approval of aducanumab and lecanemab, and approval is also expected for donanemab. Other anti-amyloid drugs such as remternetug and trontinemab are also under development...This paper outlines the current status of DMT for AD, including the clinical trial results and current applications of these drugs. It also discusses the existing challenges to improve the safety and accessibility of DMTs."

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

Donanemab: First Approval. (PubMed, Drugs) - "Donanemab recently received approval in the USA for the treatment of adults with early symptomatic Alzheimer's disease (patients with mild cognitive impairment or mild dementia stage of disease). This article summarizes the milestones in the development of donanemab leading to this first approval for Alzheimer's disease."

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

Donanemab: An innovative solution for Alzheimer's disease? (PubMed, Eur Neuropsychopharmacol) - No abstract available

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