Aduhelm (aducanumab) / Neurimmune, Eisai - LARVOL DELTA

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

An exhausted-like microglial population accumulates in aged and APOE4 genotype Alzheimer's brains (IMMUNOLOGY 2025) - "This population, which we name terminally inflammatory microglia (TIM), exhibited defects in amyloid-β clearance and acted as a key orchestrator of the recruitment of adaptive immune populations from the meninges during aducanumab therapy. Our findings cast TIM as a functionally impaired state induced by chronic neuroinflammation, suggestive of an exhausted-like microglial phenotype analogous to T cell exhaustion in the tumor microenvironment. As TIM accumulation in the AD milieu is most pronounced in APOE4 carriers and the elderly, this microglial population may be implicated in AD risk and pathology and thus presents a potential therapeutic target for AD.Keywords: Animals Rodent; Processes Cell Activation Inflammation Neuroimmunology; Techniques/Approaches Transgenic/Knockout Mice"

Clinical • Alzheimer's Disease • CNS Disorders • Oncology • APOE

Use of Model-Based Meta-Analysis to Inform the Design of Early Clinical Trials of Anti-Amyloid Beta Therapies in Alzheimer's Disease. (PubMed, CPT Pharmacometrics Syst Pharmacol) - "A general modeling framework that links drug exposures to the time course of amyloid plaque removal and amyloid-related imaging abnormalities characterized by edema and effusion (ARIA-E) was developed based on publicly available data on aducanumab, lecanemab, and donanemab. Simulations of amyloid plaque removal and ARIA-E for a hypothetical anti-Aβ mAb based on certain assumptions and scenarios provided insights into possible outcomes. Overall, the meta-analysis of published data on existing anti-Aβ mAbs could be utilized to model exposure-response relationships and the time course of amyloid plaque removal and ARIA-E incidence of new anti-Aβ mAbs and to inform the design of early clinical trials for them."

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

The efficacy and safety of anti-amyloid monoclonal antibody versus acetylcholinesterase inhibitor with an in-depth analysis across genotypes and disease stages: a systematic review and meta-analysis. (PubMed, J Prev Alzheimers Dis) - "mABs were associated with a slower progression of cognitive decline than AChEIs; however, this effect did not reach the MID. The incidence of ARIA-E with mABs was associated with APOE4 carrier status and was not indicative of treatment efficacy."

Journal • Retrospective data • Alzheimer's Disease • CNS Disorders • Dementia • Hematological Disorders • APOE

The Evolving Role of Real-World Evidence in US Reimbursement Approvals: Trends and Case Studies (2020-2024) (ISPOR 2025) - "Example: Yescarta (Gilead Sciences) - Medicare reimbursement was supported by RWE demonstrating long-term efficacy in CAR-T therapy, contributing to $1 billion in annual revenue...Example: Ozempic (Novo Nordisk) - Cardiovascular outcome data underpinned reimbursement by private insurers, generating $4.4 billion revenue...Example: Aduhelm (Eisai/Biogen) - RWE enabled Medicare's conditional approval under a coverage-with-evidence-development framework, contributing to $1 billion revenue... The proportion of US reimbursement approvals influenced by RWE increased from 15% in 2020 to 55% in 2024, reflecting a paradigm shift in payer's value assessment. Implications: These findings highlight RWE's transformative potential in shaping reimbursement strategies, providing actionable insights to align on value-based healthcare objectives"

Case study • Clinical • HEOR • Real-world • Real-world evidence • Reimbursement • US reimbursement • Cardiovascular

Analysis of Primary Causes of Delay in HTA/Reimbursement Decisions in the USA (2020-2024) (ISPOR 2025) - "Primary causes included incomplete or inconsistent submissions (e.g., Yescarta) and misalignment between sponsors and payers (e.g., Zolgensma)...Delays were driven by evidence complexity (e.g., Aduhelm), cost-effectiveness disagreements (e.g., Kymriah), and the requirement for real-world evidence (e.g., Luxturna)... Delays in HTA/reimbursement decisions in the USA during 2020-2024 were predominantly caused by incomplete submissions, disagreements over cost-effectiveness, and prolonged negotiations for high-cost therapies. Addressing these challenges, such as improving submission quality and aligning payer-sponsor expectations, could reduce delays and improve patient access."

Reimbursement • US reimbursement • Gene Therapies

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. A Markov simulation model was used incorporating literature and a prior cost-impact model of delaying AD progression. 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

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

A real-world pharmacovigilance study of adverse drug reactions associated with lecanemab and aducanumab based on WHO-VigiAccess and FAERS databases. (PubMed, Front Pharmacol) - "However, Lecanemab showed a lower risk of ARIA, cerebral hemorrhage, and severe events. These findings emphasize the need for further clinical research to clarify the long-term safety and efficacy of both drugs."

Adverse drug reaction • Adverse events • Journal • Real-world evidence • Alzheimer's Disease • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Pain

Cost-effectiveness analysis of aducanumab versus placebo for patients with mild cognitive impairment and mild Alzheimer's disease. (PubMed, BMJ Open) - "Even with the updated price being half of the original, aducanumab is still not cost-effective, underscoring the need for affordable, evidence-based AD treatments."

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

Lecanemab preferentially binds to smaller aggregates present at early Alzheimer's disease. (PubMed, Alzheimers Dement) - "Anti amyloid beta therapeutics are compared by their diffusible aggregate binding characteristics. In-vitro and brain-derived aggregates are tested using single-molecule detection. Lecanemab shows therapeutic success by binding to aggregates formed in early disease. Lecanemab binds to these aggregates with high affinity and coats them better."

Journal • Alzheimer's Disease • CNS Disorders

The Importance of Vaccines in Preventing Impending Alzheimer's Epidemic. (PubMed, Rev Recent Clin Trials) - "The use of antibodies to neutralize cytotoxic soluble amyloid-β aggregates rather than remove plaque has raised cautious hope since the monoclonal antibody BAN2401 seems to halt the course of prodromal Alzheimer's Disease (AD)...The lack of long-term protection with monoclonal antibodies that neutralize single conformers, such as aducanumab, may be due to amyloid-β pleomorphism...Since both amyloid-β and tau contribute to pathological hyperphosphorylation and work in tandem to cause Alzheimer's disease, preventive vaccinations against both should be taken into consideration. Given their affordability and simplicity, vaccines may be the only way to stop the looming Alzheimer's pandemic in many nations."

Journal • Alzheimer's Disease • CNS Disorders • Inflammation

Global experience in brain amyloid imaging. (PubMed, Semin Nucl Med) - "In high-income countries, amyloid PET is increasingly used in clinical workflows, particularly for differentiating atypical dementia cases and selecting patients for anti-amyloid therapies like aducanumab and lecanemab. Emerging trends in artificial intelligence (AI)-assisted imaging analysis and next-generation tracers promise further improvements. Addressing ethical concerns related to preclinical screening and ensuring equitable access to amyloid PET are critical for optimizing its role in neurology and nuclear medicine worldwide."

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

Clinical Benefits and Risks of Antiamyloid Antibodies in Sporadic Alzheimer Disease: Systematic Review and Network Meta-Analysis With a Web Application. (PubMed, J Med Internet Res) - "Our results showed that donanemab is more effective and has a safety profile similar to aducanumab and lecanemab, highlighting the need for treatment options with improved safety. Potential bias may have been introduced in the included trials due to unblinding caused by frequent cerebral edema and microbleeds, as well as the impact of the COVID-19 pandemic."

Clinical • Journal • Retrospective data • Review • Alzheimer's Disease • CNS Disorders • Dementia • Infectious Disease • Novel Coronavirus Disease

Medically Refractory Nonconvulsive Status Epilepticus in ARIA with Lecanemab (P1-3.017). (PubMed, Neurology) - "Seizures have been reported in aducanumab-induced ARIA...The seizure was treated with lorazepam IV and levetiracetam IV load. Continuous EEG showed focal NCSE in the right temporal region (maximal at P4/T6/O2) corresponding to the known ARIA-E location, which continued after a second dose of lorazepam with loading of lacosamide...Dr. Uhlmann has nothing to disclose."

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

A review of public comments submitted to the Centers for Medicare and Medicaid Services in response to the 2022 National Coverage Decision on treatment for Alzheimer's disease. (PubMed, J Law Biosci) - "The aducanumab controversy occurred at the intersection of multiple contentious issues; in the discussion, we contextualize our findings within these broader debates. Though Biogen pulled aducanumab from the market in early 2024, the effects of the public discourse surrounding its approval and coverage have been long-lasting and far-reaching, affecting health law, policy, and clinical practice."

Journal • Medicare • Reimbursement • US reimbursement • Alzheimer's Disease • CNS Disorders

A real-world safety surveillance study of aducanumab through the FDA adverse event reporting system. (PubMed, Front Pharmacol) - "Our real-world analysis identified ARIA-related events as the primary safety concern for aducanumab, typically occurring within 146 days of treatment initiation, with comparable safety profiles across sex but heightened risks in patients ≥75 years. These findings support aducanumab's viability as a therapeutic option while emphasizing the critical importance of rigorous monitoring protocols, particularly for ARIA events during the first year of treatment."

Adverse events • Journal • Real-world evidence • Alzheimer's Disease • CNS Disorders

MINIMIZING RISK OF AMYLOID -RELATED IMAGING ABNORMALITIES (ARIA) IN ALZHEIMER'S PATIENTS ON ANTI -AMYLOID MONOCLONAL ANTIBODY THERAPY THROUGH LOWER DOSE TITRATION (ADPD 2025) - "Slower MAB dose titration, considering the high comorbidity of CAA with AD, offers an effective, straightforward approach to reducing ARIA risk in Alzheimer's treatment."

Clinical • IO biomarker • Alzheimer's Disease • CNS Disorders • Hematological Disorders • Infectious Disease • Inflammation • APOE • Aβ42

AMPLIFYING EFFICIENCY AND ACCURACY IN DEMENTIA DRUG DEVELOPMENT (ADPD 2025) - "Recent FDA approvals of amyloid targeting treatments like aducanumab, lecanemab, and donanemab highlight ongoing challenges related to efficacy, cost, and patient access. This initiative aims to enhance the discovery, validation, and regulatory adoption of novel diagnostic and therapeutic techno logies, ultimately fostering more accurate, cost -effective, and personalized treatment interventions for dementia. The workgroup identifies up challenges and proposes the research questions for wider public to answer"

Alzheimer's Disease • CNS Disorders • Dementia

USING PLASMA P -TAU FOR PRIMARY EFFICACY IN A 1 -YEAR PHASE 1B PROOF -OF-CONCEPT STUDY BASED ON PREDICTION OF CLINICAL BENEFIT (ADPD 2025) - " Aducanumab, donanemab, and lecanemab data for plasma p -tau biomarkers and clinical assessments were obtained from the literature. Our analysis suggests that the linear correlation between p -tau and clinical outcome GST can be utilized to facilitate trial design and even to estimate clinical benefit based on treatment effects on ptau -217."

Clinical • P1 data • Alzheimer's Disease • CNS Disorders

CHARACTERISATION OF IN VITRO NEURONAL AND MICROGLIAL DISEASE MODELS TO SUPPORT DRUG DISCOVERY EFFORTS FOR NEURODEGENERATIVE DISEASES (ADPD 2025) - "Simultaneous treatment with A β and Aducanumab significantly increased the phagocytic capacity of the HMC3 cells compared to fibril treatment alone... Cellular neurodegenerative disease models focusing on fibril -induced cell toxicity, ROS production, and phagocytosis can serve as a highly efficient tool to screen neurodegenerative disease - modifying drugs before screening in vivo."

Preclinical • Alzheimer's Disease • CNS Disorders • Movement Disorders • Parkinson's Disease

CHARACTERIZATION OF AD CLINICAL PROGRESSION FOLLOWING AMYLOID-BETA PLAQUE NEGATIVITY IN CLINICAL TRIALS OF EARLY AD (ADPD 2025) - "Aims Using data from the Phase 3 aducanumab trials, ENGAGE/EMERGE and EMBARK, we investigated the trajectory and potential predictors of AD clinical progression following amyloid-beta plaque negativity (AβPN) in the absence of aducanumab treatment...Conclusions In the absence of treatment, participants with AβPN at baseline or after plaque clearance with treatment demonstrated variable rates of clinical decline, suggesting that other factors may impact disease progression following AβPN. Further characterization and prediction of disease progression following AβPN may guide clinical decisions on treatment regimen more effectively."

Clinical

DEMOGRAPHIC AND CLINICAL CHARACTERISTICS OF INITIAL PATIENTS RECEIVING AMYLOID-TARGETING TREATMENTS IN THE U.S. AFTER FDA APPROVAL (ADPD 2025) - "Aims Three amyloid targeting treatments for Alzheimer's disease have been approved in the U.S.: aducanumab (Jun 7, 2021), lecanemab (July 6, 2023) and donanemab (July 2, 2024). However, disadvantaged populations appear underrepresented in spite of their higher disease burden, given that 8% of the 65+ Medicare population are low-income dually eligible, and 9% and 7.5% are Black and Hispanic beneficiaries, respectively. Future data need to be examined to determine whether those disparities persist."

Clinical • Alzheimer's Disease • Cardiovascular • Chronic Kidney Disease • CNS Disorders • Coronary Artery Disease • Depression • Diabetes • Dyslipidemia • Heart Failure • Hypertension • Metabolic Disorders • Nephrology • Otorhinolaryngology • Psychiatry • Renal Disease

UNDERSTANDING THE ROLE OF MICROGLIA IN ANTIBODY THERAPY IN ALZHEIMER'S DISEASE (ADPD 2025) - "IHC confirms that Aducanumab treatment increases microglial clustering, as well as MHC-II expression around plaques and ELISA confirmed increased cytokine levels in soluble brain extract. This microglial phenotype could have consequences for the efficacy of microglia-targeting therapy in combination with chronic Aducanumab treatment."

Alzheimer's Disease • CNS Disorders

Generalizability of trial criteria on amyloid-lowering therapy against Alzheimer's disease to individuals with mild cognitive impairment or early Alzheimer's disease in the general population. (PubMed, Eur J Epidemiol) - "We extracted eligibility criteria for trials of aducanumab, lecanemab and donanemab, and applied these to participants with MCI and early clinical AD dementia from the population-based Rotterdam Study. Findings from recent RCTs reporting protective effects of monoclonal antibodies against amyloid-β are applicable to less than 15% of community-dwelling individuals with MCI or early AD. These findings underline that evidence for drug efficacy and safety is lacking for the vast majority of patients with MCI/AD in routine clinical practice."

Journal • Alzheimer's Disease • Cardiovascular • CNS Disorders • Cognitive Disorders • Dementia • Depression • Mood Disorders • Psychiatry • APOE