Aduhelm (aducanumab) / Neurimmune, Eisai - LARVOL DELTA

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

Lower baseline amyloid beta burden is associated with greater percent of amyloid beta positron emission tomography reduction and better clinical outcomes in the aducanumab Phase 3 trials ENGAGE and EMERGE in early Alzheimer's disease. (PubMed, J Prev Alzheimers Dis) - P3 | "The relationship between baseline amyloid beta load and treatment benefit in a large population after exposure to an amyloid beta-directed antibody provides insight into which subpopulations are likely to benefit from this class of treatment."

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

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

Aducanumab delivery via focused ultrasound-induced transient blood-brain barrier opening in vivo. (PubMed, Sci Rep) - "ADU delivery efficiency was directly correlated with the degree of BBBD, exhibiting a 7-fold increase at 0.25 MPa and a 60-fold increase at 0.42 MPa compared to sham controls, with distinct kinetic profiles observed for each condition. These findings highlight the potential of FUS-BBBD as a therapeutic strategy to enhance ADU delivery to the brain, reduce required infusion doses, and mitigate side effects associated with high-dose administration."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Oncology

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

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

Comparative efficacy, tolerability, and acceptability of aducanumab, lecanemab, and donanemab with repetitive transcranial magnetic stimulation on cognitive function in mild cognitive impairment and Alzheimer's disease: A systematic review and network meta-analysis. (PubMed, J Psychopharmacol) - "rTMS may be more effective, tolerable, and acceptable than aducanumab, lecanemab, and donanemab. Long-term direct comparison studies are needed."

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

Juxtacortical Lesion Precedes Lobar Microbleed During Anti-amyloid β Immunotherapy. (PubMed, Intern Med) - "Case Presentation A Japanese woman in her 70s with mild cognitive impairment due to AD, confirmed by positive amyloid positron emission tomography, developed a new lobar cerebral microbleed (CMB) after participating in aducanumab clinical trials...Conclusions Juxtacortical white matter hyperintensities may precede ARIA-H and may suggest cerebral amyloid angiopathy-related changes during anti-Aβ therapy. Monitoring of these lesions is essential."

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

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

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