Core Insights - Eisai Co., Ltd. and Biogen Inc. presented a two-year real-world study of lecanemab at the Alzheimer's Association International Conference 2025, highlighting its dual action against amyloid plaque and protofibrils in Alzheimer's disease [1][2] Patient Baseline and Treatment Situation - The interim study involved 178 early Alzheimer's disease patients from nine U.S. medical centers, with 57.6% diagnosed with mild cognitive impairment and 42.4% with mild Alzheimer's [3] - The average age of patients was 74.2 years, with a gender ratio of 44.6% men to 55.4% women [3] Treatment Duration and Continuation - The mean duration of lecanemab treatment was 375.4 days, with an average of 24.8 treatments per patient [4] - At the time of reporting, 87.4% of patients were still receiving treatment, with discontinuations primarily due to adverse events or personal reasons [4] Clinical Outcomes - 83.6% of patients remained stable or improved, with 86.7% of those receiving 40 or more doses over 18 months showing similar outcomes [5] - Adverse events were reported in 12.9% of patients, with the majority being asymptomatic [6][8] APOE4 Status Impact - Among 166 patients with known APOE4 status, 18.1% were homozygotes, 49.4% were heterozygotes, and 32.5% were non-carriers [7] - The incidence of ARIA was highest in homozygous carriers at 20.0%, compared to 9.8% in heterozygous and 14.8% in non-carriers [8] Blood-Based Biomarkers Utilization - 27.5% of patients were diagnosed using blood-based biomarkers, with a significant increase in testing volume observed [10][11] Treatment Satisfaction - Physician satisfaction with lecanemab's efficacy and safety averaged 8.7 out of 10, with patient satisfaction rated at 8.8 [12][13] Regulatory and Development Status - Lecanemab has been approved in 46 countries and is under review in 10, with recent approvals for maintenance dosing in the U.S. [19] - Ongoing clinical studies include the Phase 3 AHEAD 3-45 study for preclinical Alzheimer's and the Tau NexGen study for Dominantly Inherited Alzheimer's [20] Collaboration Background - Eisai and Biogen have collaborated on Alzheimer's treatments since 2014, with Eisai leading development and regulatory submissions [21] - Eisai has a long-term partnership with BioArctic for the development of lecanemab, securing global rights in 2007 [22]

Participants in the TRAILBLAZER-ALZ 2 (core) study who completed the 76-week placebo-controlled period were eligible to continue into the participant- and investigator-blinded LTE period, lasting an additional 78 weeks. Key preliminary results from the TRAILBLAZER-ALZ 2 LTE study include: Amyloid-related imaging abnormalities (ARIA) with edema/effusion (ARIA-E) and with hemorrhage/with hemosiderin deposition are side effects within the class of amyloid targeting therapies that do not usually cause any sympt ...

Core Viewpoint - China Medical System Holdings Limited (CMS) has received acceptance for the New Drug Application (NDA) of ZUNVEYL, an improved new drug for treating mild-to-moderate Alzheimer's dementia, by the National Medical Products Administration of China (NMPA) [1] Product Overview - ZUNVEYL is a new generation acetylcholinesterase inhibitor (AChEI) approved by the U.S. FDA in July 2024 for the same indication [2] - The drug works by inhibiting the breakdown of acetylcholine, thereby increasing its levels in the central nervous system, which may alleviate cognitive and memory impairments [2] - ZUNVEYL is designed to have a better gastrointestinal safety profile, with GI adverse events reported at less than 2% and no insomnia observed [2] - The product is expected to improve patient compliance and address the urgent need for safer therapies in Alzheimer's treatment [2][4] Alzheimer's Disease Context - Alzheimer's disease is a leading cause of dementia, accounting for 50% to 70% of all dementia cases, with approximately 9.83 million patients in China, of which 7.93 million have mild-to-moderate forms [3] - The aging population is expected to increase the burden of Alzheimer's disease in the future [3] Market Need and Challenges - Current treatments for Alzheimer's primarily focus on improving cognitive symptoms, but high incidences of side effects lead to a significant discontinuation rate of 55% among patients after one year [4] - The need for safer therapies is critical to improve adherence and reduce the burden on patients and caregivers [4] Licensing and Collaboration - CMS entered into a License, Collaboration, and Distribution Agreement with Alpha Cognition Inc. for ZUNVEYL, granting CMS exclusive rights to develop and commercialize the product in Asia (excluding Japan and the Middle East), Australia, and New Zealand [5] - The agreement has a term of twenty years, with potential automatic renewals every five years [5] Strategic Impact - The swift submission of the NDA in China reflects CMS's efficient resource allocation and robust registration capabilities [6] - ZUNVEYL is expected to diversify CMS's innovative drug portfolio and enhance its competitiveness in the market [6][7] - The product will complement CMS's existing central nervous system products, potentially improving treatment options for Alzheimer's patients in China [7]

Core Insights - Acumen Pharmaceuticals has reported a 40% reduction in clinical trial screening costs through the implementation of a blood-based pTau217 screening assay in its Phase 2 ALTITUDE-AD study for early Alzheimer's disease [1][3][4] - The company’s investigational product, sabirnetug, has demonstrated superior selectivity for soluble amyloid beta oligomers (AβOs) compared to other treatments, indicating a differentiated mechanism of action [5][6] Company Overview - Acumen Pharmaceuticals is focused on developing therapies targeting toxic soluble amyloid beta oligomers (AβOs) for Alzheimer's disease, with its lead candidate being sabirnetug (ACU193) [10] - The company has received Fast Track designation from the U.S. FDA for sabirnetug, which is currently in a Phase 2 clinical trial [7][10] Clinical Trial Details - The ALTITUDE-AD trial is a multi-center, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of sabirnetug in slowing cognitive decline in early Alzheimer's disease patients [9] - The trial has enrolled 542 participants across the U.S., Canada, the EU, and the UK, with a focus on improving patient-centric and cost-effective trial execution strategies [9][2] Screening Process Efficiency - The two-step screening process using plasma pTau217 biomarker testing resulted in 48% of participants meeting the threshold for confirmatory testing, with 81% of those passing the initial screening meeting amyloid positivity eligibility [4][3] - This innovative approach has led to strong enrollment rates and reduced the need for unnecessary amyloid PET scans and lumbar punctures [4][3] Mechanism of Action - Sabirnetug targets soluble AβOs, which are believed to be a significant factor in the neurodegenerative process of Alzheimer's disease, potentially slowing neurodegeneration and preventing synapse loss [5][7] - The product has shown an 8,750-fold selectivity for Aβ1-42 stabilized oligomers over Aβ1-40 monomers, highlighting its targeted action [6]

Core Insights - InMed Pharmaceuticals is presenting new preclinical data on its drug candidate INM-901 at the Alzheimer's Association International Conference (AAIC) 2025, focusing on its potential in treating Alzheimer's disease [1][5]. Group 1: Study Findings - The study evaluates INM-901 using a long-term 5xFAD mouse model, showing improvements in cognitive function, anxiety-related behavior, and sensory responsiveness [3]. - Treatment with INM-901 resulted in a significant reduction in inflammatory biomarkers, indicating a dose-dependent therapeutic effect in neuroinflammation [6]. - Behavioral improvements were observed, with cognitive function and anxiety-related behavior approaching normal levels following treatment with INM-901 [12]. Group 2: Mechanisms of Action - INM-901 targets multiple biological pathways associated with Alzheimer's disease, demonstrating anti-inflammatory action and neuroprotection by significantly reducing amyloid-beta-induced cell death [12]. - The drug promotes neurite outgrowth, enhancing neuronal connectivity and function, which aligns with observed improvements in cognition and memory [12]. - Molecular validation through mRNA data supports the behavioral findings, indicating a comprehensive therapeutic potential for INM-901 in Alzheimer's pathology [12]. Group 3: Conference Details - The AAIC 2025 will take place from July 27-31, 2025, in Toronto, Canada, serving as a premier global event for advancing research in dementia and cognitive health [5][8].

Core Viewpoint - Eli Lilly and Company has received a positive opinion from the European Medicines Agency's Committee for Medicinal Products for Human Use recommending donanemab for the treatment of early symptomatic Alzheimer's disease, with a regulatory decision from the European Commission expected soon [1][2]. Company Summary - Eli Lilly emphasizes the significance of this positive opinion as a milestone in making donanemab available to eligible patients in Europe, highlighting its potential to significantly impact those living with early symptomatic Alzheimer's disease [2]. - The company is committed to advancing scientific research through ongoing clinical trials and programs related to donanemab [2]. - Donanemab is currently marketed as Kisunla in various countries, including the United States, Japan, and the United Kingdom, and is approved for patients regardless of ApoE4 status in many regions [4]. Industry Summary - Alzheimer's disease currently affects approximately 6.9 million people in Europe, with projections indicating this number could nearly double by 2050 due to aging populations [2]. - Clinical trial data from the TRAILBLAZER-ALZ 2 and TRAILBLAZER-ALZ 6 studies support the efficacy of donanemab in slowing cognitive decline and reducing the risk of disease progression [2]. - The TRAILBLAZER-ALZ 6 trial demonstrated that a modified dosing schedule for donanemab significantly reduced the incidence of amyloid-related imaging abnormalities (ARIA-E) while maintaining similar levels of amyloid plaque removal [2].

Core Insights - Biogen Inc. will present significant data at the 2025 Alzheimer's Association International Conference (AAIC) regarding LEQEMBI (lecanemab) and BIIB080, focusing on long-term results and new treatment formulations [1][2][6] Group 1: LEQEMBI (lecanemab) Developments - The upcoming presentations will include 48-month results from the Clarity AD open-label extension, real-world evidence, and insights into a subcutaneous formulation for maintenance dosing of LEQEMBI [1][2][6] - LEQEMBI is a humanized IgG1 monoclonal antibody targeting amyloid-beta, which received traditional FDA approval on July 6, 2023, for treating Alzheimer's disease [8][9] Group 2: BIIB080 Investigational Therapy - BIIB080 is an investigational antisense oligonucleotide (ASO) therapy targeting tau protein, currently in a Phase 2 clinical study for early Alzheimer's disease [5][6] - The CELIA trial will provide baseline characteristics of participants, contributing to the understanding of tau-targeted therapies [2][7] Group 3: Educational Initiatives - Biogen will host an interactive booth at AAIC to educate attendees on the role of tau in Alzheimer's disease and will launch a new e-learning module on KnowTau.com [4][6] - The educational program aims to bridge research and clinical practice regarding tau therapies and biomarkers [7]

Core Viewpoint - NKGen Biotech has initiated the administration of troculeucel, an autologous NK cell therapy, to a patient with mild-stage Alzheimer's disease under a compassionate use IND authorization from the FDA, marking a significant step in expanding treatment options for patients who do not respond to existing therapies [1][2]. Company Overview - NKGen Biotech is a clinical-stage biotechnology company focused on developing and commercializing innovative autologous and allogeneic NK cell therapeutics, headquartered in Santa Ana, California [4]. - Troculeucel, the company's novel cell-based immunotherapeutic drug candidate, is being developed for neurodegenerative disorders and various cancers, with its International Nonproprietary Name (INN) approved by the WHO [5]. Clinical Development - The ongoing double-blind randomized Phase 2a trial by NKGen is primarily focused on moderate-stage Alzheimer's disease, while the recent IND authorization allows exploration in mild-stage Alzheimer's, particularly for patients unresponsive to first-line therapies [2]. - Clinical experience with troculeucel indicates it is well-tolerated and capable of crossing the blood-brain barrier, improving levels of amyloid, α-synuclein, and tau proteins in cerebrospinal fluid, and reducing neuroinflammation [3]. Industry Context - Currently, there are two FDA-approved amyloid-targeting therapies for Alzheimer's patients with mild cognitive impairment, which slow cognitive decline but do not halt disease progression or improve cognitive function [3]. - The exploration of troculeucel in patients progressing on standard therapies could provide insights into disease mechanisms and support combination treatment strategies [3].

Core Viewpoint - The FDA has approved a label update for Kisunla (donanemab-azbt), introducing a new dosing schedule that significantly reduces the incidence of amyloid-related imaging abnormalities with edema/effusion (ARIA-E) while maintaining its efficacy in amyloid plaque removal and P-tau217 reduction [1][2][3]. Group 1: Dosing Schedule and Efficacy - The modified titration schedule resulted in a 41% reduction in ARIA-E incidence at 24 weeks and a 35% reduction at 52 weeks compared to the original dosing regimen [2][4]. - The new dosing regimen involves a gradual titration, shifting a single vial from the first dose to the third dose, achieving the same total dosage by week 24 [2][3]. - Amyloid plaque levels were reduced by an average of 67% from baseline in the modified titration group, compared to 69% in the original dosing group at the primary endpoint of 24 weeks [4]. Group 2: Clinical Study Insights - The TRAILBLAZER-ALZ 6 study enrolled 843 participants aged 60-85 and focused on the effects of different dosing regimens on ARIA-E [7]. - The primary endpoint was the proportion of participants with any occurrence of ARIA-E by week 24, showing a 14% incidence in the modified titration group versus 24% in the original group [4]. - No new adverse reactions were identified in the study, although higher rates of hypersensitivity and infusion-related reactions were noted [4]. Group 3: Company Commitment and Support Services - Eli Lilly emphasizes its commitment to patient safety and the advancement of Alzheimer's treatment through this updated dosing strategy [2][3]. - Lilly Support Services for Kisunla offers assistance to patients, including coverage determination, care coordination, and personalized resources [5].

Alzheimer's Disease Burden and Current Treatments - Alzheimer's accounts for 60-80% of dementia cases[6] - It affects 6.9 million Americans[6] - Alzheimer's is the 5th leading cause of death for those aged 65+[6] - The U.S annual financial impact of Alzheimer's and other dementias is $360 billion[6] - Current treatments primarily target amyloid-beta plaques but have limitations, including limited therapeutic effects and side effects[14, 15] INM-901: A Multifactorial Approach - INM-901 is an orally available small molecule drug candidate that can cross the blood-brain barrier[8, 21, 48] - It acts as a preferential signaling agonist for CB1/CB2 receptors and impacts the PPAR signaling pathway[8, 18, 21] - In vitro studies show INM-901 demonstrates neuroprotective effects and increased neurite outgrowth, signifying enhanced neuronal function[8, 27, 28, 29, 32] - Preclinical in vivo studies suggest INM-901 improves behavior and cognitive function, reduces neuroinflammation, and enhances neuronal function[8, 39, 42, 44] - Molecular data indicates INM-901 reduces pro-inflammatory genes and elevates neuronal function genes[42]