Assessment of Safety and Feasibility of Exablate Blood-Brain Barrier Disruption for the Treatment of Patients With With Mild Cognitive Impairment (MCI) or Mild Alzheimer's Disease (AD) Undergoing Standard of Care Monoclonal Antibody (mAb) Therapy

The purpose of this study is to assess the safety and feasibility of administering standard of care monoclonal antibody (mAb) infusion therapy in combination with opening the blood-brain barrier with the Exablate Model 4000 Type 2 device in patients with mild Alzheimer's disease (AD) or mild cognitive impairment (MCI).

Start Date14 Jul 2022

Sponsor / Collaborator

West Virginia University

[+1]

NCT05310071

/ TerminatedPhase 3

A Phase 3b/4 Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Verify the Clinical Benefit of Aducanumab (BIIB037) in Participants With Alzheimer's Disease

The primary objective of this study is to verify the clinical benefit of monthly doses of aducanumab in slowing cognitive and functional impairment as measured by changes in the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) score as compared with placebo in participants with early Alzheimer's disease.

Start Date02 Jun 2022

Sponsor / Collaborator

Biogen, Inc.

NCT05216887

/ CompletedPhase 1

A Randomized, Open-Label, Parallel-Arm Study to Assess the Pharmacokinetic Comparability of 2 Fixed Subcutaneous Doses of Aducanumab (BIIB037) With a Single, Weight-Based Intravenous Dose in Healthy Volunteers

The primary objective of the study is to evaluate the pharmacokinetic (PK) comparability of 2 fixed subcutaneous (SC) doses of aducanumab with a single, weight-based intravenous (IV) dose of aducanumab in healthy volunteers. The secondary objectives of the study are to assess the safety and tolerability of aducanumab administered SC in healthy volunteers and to characterize additional PK parameters of 2 fixed SC doses of aducanumab and a single, weight-based IV dose of aducanumab.

Start Date01 Feb 2022

Sponsor / Collaborator

Biogen, Inc.

100 Clinical Results associated with Aducanumab-avwa

100 Translational Medicine associated with Aducanumab-avwa

100 Patents (Medical) associated with Aducanumab-avwa

602

Literatures (Medical) associated with Aducanumab-avwa

31 Dec 2025·mAbs

Analytical development and application of a targeted liquid chromatography-tandem mass spectrometry assay for chimeric aducanumab

Article

Author: Eldridge, Kierra ; Hansen, Kasi ; Territo, Paul R. ; Quinney, Sara K. ; Haynes, Kathryn A. ; Mosley, Amber L. ; Charbe, Nitin ; Doud, Emma H. ; Arrivalagan, Jaison ; Da Silva, Lais ; Rizzo, Stacey J. Sukoff

A sensitive and specific liquid chromatography-tandem mass spectrometry assay was developed for the quantification of chimeric aducanumab (chAdu), a therapeutic antibody targeting pathological amyloid plaques in Alzheimer's disease, in murine biological matrices. This method addresses the challenges of quantifying biotherapeutics in multiple tissue types within preclinical animal models with complex genetic backgrounds, where traditional enzyme-linked immunosorbent assay (ELISA) methods may suffer from interference and limited sensitivity. The assay uses parallel reaction monitoring on a Lumos Tribrid Orbitrap mass spectrometer, coupled with an Evosep LC system, and AssayMap Bravo-based automated sample processing. Key features include protein A enrichment for improved sensitivity, optimized peptide selection based on sequence uniqueness and ionization response, and incorporation of stable isotope-labeled peptides for accurate quantification. Assay performance was evaluated for selectivity, repeatability, and stability. The fit-for-purpose assay was successfully applied to quantify chAdu in both mouse cortex and plasma samples obtained from a pilot pharmacokinetic study of a mouse model of amyloid plaque deposition. This targeted mass spectrometry workflow offers a robust and reproducible alternative to ELISA for preclinical biotherapeutic analysis, particularly when dealing with complex biological samples.

01 Nov 2025·NEUROSCIENCE

Anti-amyloid monoclonal antibody therapies in Alzheimer’s disease – a scoping review

Article

Author: Al Shibli, Aous N ; Pedersen, Shona ; Shaito, Abdullah ; Al-Maadhadi, Mazyona J M B ; Elamin, Shahd Abubaker ; Zolezzi, Monica

Alzheimer's disease (AD) is a progressive neurodegenerative disorder affecting millions worldwide, and with advancements in the medical field, Anti-amyloid monoclonal antibodies (AA mAbs) targeting amyloid-β have emerged as potential disease-modifying agents altering AD pathology. This scoping review mapped the characteristics, patterns, and gaps in clinical trials investigating the efficacy and safety of AA mAbs in AD treatments, with focus on cognitive, functional, biochemical, imaging, and safety outcomes. It highlighted patterns, gaps, and limitations of the existing literature. A systematic search of PubMed/MEDLINE, Embase, Scopus, and Web of Science was conducted for studies published since inception to February 2022, and eligible studies that investigated efficacy and safety outcomes of AA mAbs in treatment of AD were included. A majority of the included trials reported a combination of cognitive, functional, biochemical, and imaging outcomes. Across the sample, reductions in amyloid burden were frequently reported (10 trials), with a smaller subset of studies reporting significant cognitive and functional improvements (4 trials), primarily lecanemab and aducanumab in addition to one pooled analysis of solanezumab. ARIA-E and ARIA-H were frequently reported among the safety concerns, particularly in high-dose and APOE ε4 carrier populations. Notable limitations were observed in the reviewed literature including a disconnect between biomarker changes and consistent clinical benefits and, importantly, limited population diversity and patient-reported outcomes. This review highlights the need for rigorous, diverse, and patient-centered research. Addressing these gaps is critical in ensuring safe, effective, and equitable treatment for all patients living with Alzheimer's disease.

01 Nov 2025·EUROPEAN JOURNAL OF PHARMACOLOGY

Mapping the evolving landscape of lecanemab research in Alzheimer's Disease: A bibliometric analysis

Article

Author: Xu, Dingwen ; Shen, Jiaxing ; Ma, Ruijia ; Zhao, Xu ; Yang, Zhe

BACKGROUND:

Lecanemab, a monoclonal antibody that targets amyloid-beta aggregates, has emerged as a promising therapeutic for Alzheimer's disease (AD). AD is a progressive neurodegenerative disorder characterized by cognitive decline and amyloid pathology. Research on the use of lecanemab in treating AD has increased; however, no relevant bibliometric analyses have been conducted. To address this gap, this study employed bibliometric methods to search for the relevant literature and analyze research trends investigating AD and lecanemab.

METHODS:

We performed a literature search of the Web of Science core database for studies investigating AD and lecanemab, published from database inception up to April 3rd, 2025. After rigorous screening, Excel, VOSviewer, and CiteSpace were used to perform a bibliometric analysis of publications, citations, and collaboration networks among countries, institutions, and authors, along with cluster and burst analyses of keywords. Coremine was used for text mining entries significantly related to AD and lecanemab.

RESULTS:

The number of studies published on AD and lecanemab has increased annually. The countries with the highest publication output were the United States, the United Kingdom, and China. The leading institutions that produced the most articles were Eisai Inc. (Bunkyo City, Tokyo, Japan), Uppsala University (Uppsala, Sweden), and Harvard Medical School (Boston, MA, USA). The top three authors were Lars Lannfelt, Shobha Dhadda, and Michio Kanekiyo. The most prolific journals included The Journal of Alzheimer's Disease, Alzheimer's and Dementia, and Ageing Research Reviews. The most cited article was "Lecanemab in Early Alzheimer's Disease," by Van Dyck et al., published in The New England Journal of Medicine in 2023, which has accrued 172 citations. The 10 most frequently occurring keywords were Alzheimer's disease, lecanemab, dementia, aducanumab, amyloid-beta, immunotherapy, tau, a-beta, mouse model, and donanemab. Text mining revealed that drugs, anatomical structures, chemical molecules, genes, diseases, and procedures were significantly associated with both AD and lecanemab.

CONCLUSION:

The bibliometric and text mining analysis revealed trends in research investigating the correlation between lecanemab and AD. It analyzed the cooperation among countries, regions, and authors, highlighting recent research hotspots. These data offer objective insights for scientific research and clinical practice on lecanemab and AD. These findings provide a roadmap for prioritizing clinical trials, optimizing drug development strategies, and addressing knowledge gaps in amyloid-targeted therapies.

877

News (Medical) associated with Aducanumab-avwa

02 Dec 2025

·www.businesswire.com

Alzheon Announces Peer-Reviewed Publication Providing Evidence for Hippocampal Volume as Surrogate Marker for Clinical Benefit and Neurodegeneration in Early Alzheimer’s Disease

FRAMINGHAM, Mass.--(BUSINESS WIRE)--Alzheon, Inc., a clinical-stage biopharmaceutical company developing a broad portfolio of investigational therapies and diagnostic assays for patients with Alzheimer’s disease (AD) and other neurodegenerative disorders, today announced the peer-reviewed publication: “Hippocampal Atrophy on Magnetic Resonance Imaging as a Surrogate Marker for Clinical Benefit and Neurodegeneration in Early Symptomatic Alzheimer’s Disease: Synthesis of Evidence from Observational and Interventional Trials”, in the scientific journal CNS Drugs. The full text is available online at: https://link.springer.com/article/10.1007/s40263-025-01251-y The AD field urgently needs to improve treatments, and surrogate biomarkers are essential for accelerating drug development. This review, co-authored by Alzheon’s scientists and leading AD neuroimaging researchers and clinicians, analyzes clinical evidence for using hippocampal volume as a surrogate marker. The results show that shrinkage of the hippocampus is closely linked to memory decline and disease progression, and that the hippocampus of Early Alzheimer's patients responds sensitively to disease-modifying therapies. Therefore, hippocampal volume (HV) may be a reliable and measurable surrogate used to assess clinical benefits in Early Alzheimer’s disease. Key Findings Predictive biomarker: HV atrophy closely tracks cognitive decline in both observational and interventional data, making HV a reliable and sensitive marker of disease progression. Therapeutic sensitivity: Multiple clinical studies, including those evaluating lecanemab, donanemab, and valiltramiprosate/ALZ-801, have shown that interventions slowing cognitive decline are also associated with reduced hippocampal atrophy. These findings highlight the responsiveness of hippocampal volume to therapeutic intervention. Clinical relevance: The analysis established a hippocampal volume preservation threshold of ≥40 mm³ that correlates with significant cognitive improvement at the Mild Cognitive Impairment (MCI) stage, underscoring hippocampal volume as a potential regulatory endpoint for early Alzheimer’s disease. “Developing reliable non-invasive imaging-based surrogate markers is essential to accelerate Alzheimer’s drug development,” said Murali Doraiswamy, MBBS, FRCP, Professor of Psychiatry and Medicine at Duke University* and an expert in Alzheimer’s imaging & biomarkers. “Hippocampal atrophy, a structural hallmark of neuronal losses and neurodegeneration in AD, reflects the neurodegenerative process more directly than amyloid plaque deposition or clearance. It could serve as a predictive regulatory endpoint for evaluating new therapies in early symptomatic AD targeting multiple pathways beyond amyloid.” Clinical trials involving about 10,000 participants tested anti-amyloid and anti-oligomer treatments, finding that reduced hippocampal atrophy was accompanied by slower cognitive decline over 18–24 months. Specifically, valiltramiprosate trials showed notable links between preserving hippocampal volume and better cognitive results for individual patients (r = –0.40 to –0.44, p <0.005), as well as consistency between hippocampal volume and microstructural integrity on diffusion tensor imaging scans. The research also identified that protecting 40 mm³ of hippocampal tissue was the minimum amount needed to see meaningful cognitive benefits in people with mild cognitive impairment (MCI). “The hippocampus is among the first regions of the brain affected by Alzheimer’s disease. Our findings indicate that preservation of hippocampal volume, reflecting reduced atrophy, is directly associated with clinical improvement as determined by established cognitive assessment measures,” said Susan Abushakra MD, Chief Medical Officer of Alzheon and the study’s lead author. “By confirming this association across both observational studies and randomized controlled trials—including data from valiltramiprosate/ ALZ-801 demonstrating microstructural integrity supporting hippocampal protection—we present strong evidence that hippocampal volume may serve as a surrogate marker for neuroprotection, clinical efficacy, and disease modification in early-stage Alzheimer’s disease." These results reinforce the consideration of hippocampal volume as an early, robust, sensitive, and clinically significant indicator of neurodegeneration, underscoring its prospective utility in forthcoming Alzheimer's disease clinical trials. The hippocampus is essential for memory function, so its preservation provides a demonstrable measure of neuroprotection. "Our analyses highlight the role of hippocampal volume as an important intermediary linking biomarker changes to clinically meaningful benefits," stated John Hey, Ph.D., Chief Scientific Officer at Alzheon. "Hippocampal atrophy is a key marker within the ‘N’ neurodegeneration category of the A/T/N classification, reflecting neuronal loss and the structural decline characteristic of Alzheimer's disease. Consequently, mitigating brain atrophy is among the most significant indicators of disease modification in Alzheimer's disease. These results further substantiate our clinical findings in two valiltramiprosate studies involving APOE4 homozygotes and carriers, where retention of hippocampal integrity was strongly associated with reduced cognitive decline." * Dr. Doraiswamy is an advisor to Alzheon, Inc. and a minor shareholder. He also serves as an advisor to several other businesses, government agencies and advocacy groups. About ALZ-801 Valiltramiprosate/ALZ-801 is an investigational oral agent currently in Phase 3 development as a potential first-in-class, disease-modifying treatment for Alzheimer’s disease.3-7,9,12 Valiltramiprosate is designed to inhibit the formation of neurotoxic soluble beta amyloid oligomers that contribute to cognitive decline in individuals with AD.3-7,9,14 Preclinical mechanism-of-action studies have demonstrated that ALZ-801 can completely block the formation of these neurotoxic oligomers at the dosage used in Phase 3 clinical trials.3,9,12,14 Valiltramiprosate employs an enveloping molecular mechanism of action intended to prevent the aggregation of soluble amyloid oligomers in the human brain, 14 which are associated with the onset and progression of cognitive impairment in AD patients.3,4,7,9,10 In recognition of its therapeutic promise, valiltramiprosate received Fast Track designation from the U.S. Food and Drug Administration in 2017 for the treatment of Alzheimer’s disease. Clinical trial data indicate that valiltramiprosate exhibits strong clinical efficacy at the MCI stage, and a favorable safety profile, with no observed increase in the risk of brain vasogenic edema.5-10,13,15 The initial Phase 3 program for valiltramiprosate targets Early AD patients who are homozygous for the apolipoprotein ε4 allele (APOE4/4), with plans to expand future research to include AD treatment and prevention in individuals carrying one copy of the APOE4 gene.3–10 Valiltramiprosate APOLLOE4 Phase 3 Trial An Efficacy and Safety Study of Valiltramiprosate in APOE4/4 Early Alzheimer's Disease Subjects (NCT04770220): This trial was designed to evaluate the efficacy, safety, biomarker and imaging effects of 265 mg twice daily oral dose of valiltramiprosate in Early AD subjects with two copies of the apolipoprotein ε4 allele (APOE4/4 homozygotes), who constitute approximately 15% of Alzheimer's patients. This double-blind, randomized trial compared oral valiltramiprosate to placebo treatment over 78 weeks. The APOLLOE4 trial was supported by a grant from the National Institute on Aging to Alzheon, with Susan Abushakra as the principal investigator. Valiltramiprosate APOLLOE4 Long Term Extension Trial (Phase 3 LTE) An ongoing long-term extension of the trial, APOLLOE4-LTE, evaluates valiltramiprosate in subjects who complete the core APOLLOE4 study for an additional 104 weeks of treatment for a total of 182 weeks, or 3.5 years, over the core and LTE study. This LTE study is currently ongoing in the US, UK, and Canada (NCT06304883). Valiltramiprosate Phase 2 Biomarker Trial Biomarker Effects of Valiltramiprosate in APOE4 Carriers with Early Alzheimer's Disease (NCT04693520): This trial was designed to evaluate the effects of 265 mg twice daily oral dose of valiltramiprosate on biomarkers of AD pathology in subjects with Early AD, who have either the APOE4/4 or APOE3/4 genotype and constitute 65-70% of Alzheimer's patients. The primary outcome was the change from baseline in plasma p-tau181. The trial also included evaluation of clinical efficacy, safety, tolerability, and pharmacokinetic profile of valiltramiprosate over 104 weeks of treatment. A completed long-term extension of the trial evaluated the same dose of valiltramiprosate for an additional 104 weeks of treatment for a total of 208 weeks.2,6,7 About Alzheon Alzheon, Inc. is a clinical-stage biopharmaceutical company dedicated to advancing a diverse portfolio of product candidates and diagnostic assays for individuals affected by Alzheimer’s disease and other neurodegenerative disorders. The company is focused on innovating therapeutic solutions that directly target the underlying pathology of neurodegeneration. Its lead Alzheimer's clinical candidate, valiltramiprosate/ALZ-801, is a first-in-class oral agent currently in Phase 3 clinical development as a potentially disease-modifying treatment for Alzheimer’s disease. Valiltramiprosate is an orally administered small molecule shown in preclinical studies to completely inhibit the formation of neurotoxic soluble amyloid oligomers. Leveraging clinical expertise and a robust technology platform, Alzheon pursues drug discovery and development using a precision medicine approach that incorporates individual genetic and biomarker profiles, aiming to advance therapies with meaningful benefits for patients. Alzheon Scientific Publications 1Abushakra S, et al: Hippocampal Atrophy on Magnetic Resonance Imaging as a Surrogate Marker for Clinical Benefit and Neurodegeneration in Early Symptomatic Alzheimer’s Disease: Synthesis of Evidence from Observational and Interventional Trials, Drugs 2025. 2Abushakra S, et al: Clinical Efficacy, Safety and Imaging Effects of Oral Valiltramiprosate in APOEε4/ε4 Homozygotes with Early Alzheimer’s Disease: Results of the Phase III, Randomized, Double-Blind, Placebo-Controlled, 78-Week APOLLOE4 Trial, Drugs 2025; 85, 1455-1472. 3Pearson D, et al: Polymorph Analysis of ALZ-801 (Valiltramiprosate), a Valine-Conjugated Oral Prodrug of Tramiprosate in Late-Stage Clinical Development for Alzheimer’s Disease, Journal of Chemical Crystallography 2025; 55, 206-215. 4Hey JA, et al: Clinical Pharmacokinetics of Oral ALZ-801/Valiltramiprosate in a Two-Year Phase 2 Trial of APOE4 Carriers with Early Alzheimer’s Disease, Clinical Pharmacokinetics 2025; 64, 407-424. 5Aye S, et al: Point of View: Challenges in Implementation of New Immunotherapies for Alzheimer's Disease, The Journal of Prevention of Alzheimer’s Disease 2025;12(1):100022. 6Abushakra S, et al: APOLLOE4 Phase 3 Study of Oral ALZ-801/Valiltramiprosate in APOE ε4/ε4 Homozygotes with Early Alzheimer’s Disease: Trial Design and Baseline Characteristics Alzheimer’s & Dementia 2024; 10(3): e12498. 7Tolar M, et al: The Single Toxin Origin of Alzheimer’s Disease and Other Neurodegenerative Disorders Enables Targeted Approach to Treatment and Prevention, International Journal of Molecular Sciences 2024; 25(5), 2727. 8Hey JA, et al: Analysis of Cerebrospinal Fluid, Plasma β Amyloid Biomarkers, and Cognition from a 2-Year Phase 2 Trial Evaluating Oral ALZ-801/Valiltramiprosate in APOE4 Carriers with Early Alzheimer’s Disease Using Quantitative Systems Pharmacology Model, Drugs 2024; 84(7), 825-839. 9Hey JA, et al: Effects of Oral ALZ-801/Valiltramiprosate on Plasma Biomarkers, Brain Hippocampal Volume, and Cognition: Results of 2-Year Single Arm, Open Label, Phase 2 Trial in APOE4 Carriers with Early Alzheimer’s Disease, Drugs 2024; 84(7), 811-823. 10Tolar M, et al: Neurotoxic Soluble Amyloid Oligomers Drive Alzheimer’s Pathogenesis and Represent a Clinically Validated Target for Slowing Disease Progression, International Journal of Molecular Sciences 2021; 22(12), 6355. 11Abushakra S, et al: APOE ε4/ε4 Homozygotes with Early Alzheimer’s Disease Show Accelerated Hippocampal Atrophy and Cortical Thinning that Correlates with Cognitive Decline, Alzheimer’s & Dementia 2020; 6(1): e12117. 12Tolar M, et al: Aducanumab, Gantenerumab, BAN2401, and ALZ-801—the First Wave of Amyloid-Targeting Drugs for Alzheimer’s Disease with Potential for Near Term Approval, Alzheimer’s Research & Therapy 2020; 12(1): 95. 13Tolar M, et al: The Path Forward in Alzheimer’s Disease Therapeutics: Reevaluating the Amyloid Cascade Hypothesis, Alzheimer’s & Dementia 2020; 16(11):1553-1560. 14Hey JA, et al: Discovery and Identification of an Endogenous Metabolite of Tramiprosate and Its Prodrug ALZ-801 that Inhibits Beta Amyloid Oligomer Formation in the Human Brain, CNS Drugs 2018; 32(9): 849-861. 15Hey JA, et al: Clinical Pharmacokinetics and Safety of ALZ-801, a Novel Prodrug of Tramiprosate in Development for the Treatment of Alzheimer’s Disease, Clinical Pharmacokinetics 2018; 57(3): 315-333. 16Abushakra S, et al: Clinical Effects of Tramiprosate in APOE4/4 Homozygous Patients with Mild Alzheimer’s Disease Suggest Disease Modification Potential, Journal of Prevention of Alzheimer’s Disease 2017; 4(3): 149-156. 17Kocis P, et al: Elucidating the Aβ42 Anti-Aggregation Mechanism of Action of Tramiprosate in Alzheimer’s Disease: Integrating Molecular Analytical Methods, Pharmacokinetic and Clinical Data, CNS Drugs 2017; 31(6): 495-509. 18Abushakra S, et al: Clinical Benefits of Tramiprosate in Alzheimer’s Disease Are Associated with Higher Number of APOE4 Alleles: The “APOE4 Gene-Dose Effect,” Journal of Prevention of Alzheimer’s Disease 2016; 3(4): 219-228.

Phase 2Phase 3Clinical ResultFast Track

02 Dec 2025

·www.biospace.com

I Remember Aduhelm. The Return of Roche in Alzheimer’s Is a Turning Point

iStock, Volodymyr Kryshtal After covering the Alzheimer’s space through every high and low, BioSpace ’s Annalee Armstrong welcomes back Roche for the 2026 Alzheimer’s Renaissance. We all have those news moments in our lives where we remember exactly where we were. For me, I was sitting on a well-worn leather couch in a frigid Florida AirBnb—cold because the AC had been cranked to the highest setting by warring family members. It was June 2021. Around me was pure chaos. My 15-month-old son was ripping books off the shelves; two pre-teens were running amuck and arguing. I opened my laptop hoping for a nice quiet morning before I could sneak away to the beach after deadline. But then it happened: the FDA approved Aduhelm. It was a controversial—and expensive—Alzheimer’s disease medicine that would eventually be pulled from the market after being found ineffective. But already at the time, there were dissenting voices that were overruled to secure its greenlight. In hindsight it’s clear that the whole saga scarred Biogen’s reputation, and maybe even damaged the entire industry’s quest to find new medicines for the devastating neurodegenerative disease. I was drawn back to this moment on that ugly couch on Tuesday when Roche announced a successful Phase I/II trial for its antibody trontinemab. After Aduhelm’s epic failure, Biogen went on with partner Eisai to eventually get Leqembi approved for Alzheimer’s. Eli Lilly followed with Kisunla. Roche was player three in the battle for a disease-modifying Alzheimer’s drug. The company experienced dramatic highs and lows in this quest, just like everyone else in this disease space, as the unforgiving clinical environment claimed candidate after candidate. But while Lilly and Biogen surged ahead, Roche’s Genentech unit was forced to back off, recircle the wagons for what felt like the 1,000th time and start over after the definitive failure of gantenerumab in 2022. Through it all, Roche’s scientists kept pushing, contributing to the market in other ways with a new test that has aided diagnosis so that patients can get on treatments like Leqembi and Kisunla. They never stopped working on treatment options, either, fine tuning their Brainshuttle technology to foster the movement of medicine across the blood-brain barrier. Several years after the monoclonal antibody class entered the market for Alzheimer’s, we know it hasn’t been a perfect roll out. The diagnostic hurdles had to be figured out and doctors had to adjust to the new treatment paradigm. I remember feeling deeply unsettled when the FDA approved Aduhelm and the years that followed that spectacular regulatory and commercial failure were riddled with turmoil for researchers and for patients. But here we are in 2025 in a much more hopeful space. Patients have options to try. They have more coming in the clinic from pharma and biotech. Several key readouts from Biogen and Lilly are expected in the months ahead. And Roche is back. So now with three major pharmas pushing to expand in Alzheimer’s, more patients than ever will have increasingly effective options. May 2026 be the year of the Alzheimer’s renaissance once again. Earnings As Biogen Nears Presymptomatic Alzheimer’s Readout for Leqembi, Can Doctors Be Convinced? To expand the population for the anti-amyloid Alzheimer’s drugs, Lilly and Biogen are testing presymptomatic patients. Will doctors be open to this paradigm-shifting change? October 30, 2025 · 2 min read · Annalee Armstrong Read More

Drug Approval

19 Nov 2025

·www.businesswire.com

Alzheon to Present Multiple Clinical, Neuroimaging and Modeling Results for Oral Valiltramiprosate/ALZ-801 from Phase 2 and 3 Studies at CTAD Conference in San Diego, December 1–4, 2025

FRAMINGHAM, Mass.--(BUSINESS WIRE)--Alzheon, Inc., a clinical-stage biopharmaceutical company advancing innovative therapeutics and diagnostics for patients with Alzheimer’s disease (AD), today announced it will present new efficacy and safety data from the Phase 2 study long term extension over 3 years, and quantitative systems pharmacology (QSP) analyses for its lead investigational therapy, valiltramiprosate/ALZ-801, during the 18th Clinical Trials on Alzheimer’s Disease (CTAD) conference in San Diego, California. Positive clinical and structural brain outcomes from the APOLLOE4 Phase 3 program continue to strengthen the case for valiltramiprosate as a potential breakthrough oral treatment for the high-risk APOE4 population. Valiltramiprosate is an investigational oral therapeutic agent in Phase 3 trials that works upstream of anti-amyloid antibodies by preventing neurotoxic amyloid oligomer formation. As a prodrug of tramiprosate with improved pharmacokinetics and brain penetration, it targets early amyloid aggregation, which is key in Alzheimer’s disease progression. Valiltramiprosate aims to preserve cerebral structure and function in individuals with early-stage Alzheimer’s disease, with a particular emphasis on APOE4/4 homozygotes, who represent the highest genetic risk group and experience rapid disease progression with limited available treatment options. “Positive clinical and structural brain outcomes from the APOLLOE4 Phase 3 program continue to strengthen the case for valiltramiprosate as a potential breakthrough oral treatment for the high-risk APOE4 population,” said David Watson, PhD, Founder & Principal Investigator, Alzheimer’s & Research Treatment Center. “Therapies that safely reduce the formation of toxic amyloid oligomers at the start of the disease process have the potential to shift how and when we treat Alzheimer’s disease. ALZ-801 has shown that promise in clinical trials.” Quantitative Systems Pharmacology (QSP) analyses of long term valiltramiprosate clinical data to be presented at CTAD, predict preservation of hippocampal volume and broad reduction in neurodegeneration, consistent with meaningful slowing of clinical decline in early symptomatic AD. Studies show that valiltramiprosate binds monomeric beta amyloid, blocking the creation of harmful oligomers associated with synaptic toxicity and neuron loss. QSP analysis links reduced toxic oligomer formation to greater preservation of hippocampal volume, less neurodegeneration, and slower disease progression, especially in APOE4/4 individuals who have higher levels of neurotoxic amyloid. Favorable long-term safety results over 3 years with no ARIA events continue to differentiate valiltramiprosate from other potential treatment options. “These new findings support our upstream approach in altering the course of Alzheimer’s disease and highlight valiltramiprosate’s potential as a safe, effective oral therapy for APOE4 patients,” said John Hey, PhD, Alzheon Chief Scientific Officer. “Consistent clinical, imaging, and molecular modeling data provide a solid basis for regulatory discussions and precision medicine development of our lead product.” Details of Presentations at CTAD Monday 3:00 p.m. – Tuesday 5:30 p.m. Poster: Effects of Oral Valiltramiprosate on Clinical Efficacy, Safety and Brain Volume Outcomes in APOE4/4 Homozygotes with Early AD: Topline Results of APOLLOE4 Randomized, Placebo-Controlled 78-Week Multi-Center Trial Presenter: Dr. Susan Abushakra, Chief Medical Officer, Alzheon, Inc. Poster: Clinical Stabilization in APOE4 Carriers with MCI over 3 Years Correlates with Reduced Hippocampal Atrophy in a Phase 2 Long-Term Extension Study with Oral Valiltramiprosate Presenter: Dr. John Hey, Chief Scientific Officer, Alzheon, Inc. Poster: Correlations of Valiltramiprosate Effects on Hippocampal Volume and Cortical Thickness with Clinical Outcomes in APOE4/4 Subjects with MCI: Prespecified Analysis from the 78-Week APOLLOE4 Phase 3 Trial Presenter: Dr. Aidan Power, Chief Development Officer, Alzheon, Inc. Poster: Effects of the Oral Anti-Amyloid Agent Valiltramiprosate on Measures of Microstructural Integrity: Diffusion MRI Results of the Phase 3 APOLLOE4 Trial in APOE4/4 Homozygotes with Early AD Presenter: Dr. Earvin Liang, VP of Clinical Development, Alzheon, Inc. Poster: The Safety and ARIA Effects of the Oral Anti-Amyloid Agent Valiltramiprosate from the Phase 3 APOLLOE4 Trial in APOE4/4 Homozygotes with Early AD Presenter: Dr. David Watson, CEO, Alzheimer’s Research & Treatment Center Poster: Biomarker Positive APOE4 Carriers with MCI Show Stability on MMSE Over 208-weeks of Treatment with Oral Valiltramiprosate in a Phase 2 Multi-Center-Single-Arm Trial Presenter: Dr. Patrick Kesslak, Senior Research Fellow, Alzheon, Inc. Wednesday 7:15 a.m. – 5:30 p.m. Poster: Valiltramiprosate/ ALZ-801 Inhibits Amyloid Oligomer Formation: Quantitative Systems Pharmacology Analysis of A-Beta Aggregation Dynamics & Impact on AD Progression Presenter: Dr. John Hey, Chief Scientific Officer, Alzheon, Inc. Poster: Valiltramiprosate Prevents Hippocampal Atrophy & Clinical Decline in An Early Symptomatic APOE4/4 AD Subpopulation in Phase 3 Study via Potential Neurogenesis/ Neuroplasticity Action Presenter: Dr. Jeremy Yu, Senior Research Fellow, Alzheon, Inc. Poster: Quantitative System Pharmacology Analysis of Oral Valiltramiprosate Natural Trajectory of Alzheimer’s Disease Progression by APOE4 Genotype: Contribution of Anti-Amyloid Oligomer & APOE4 Corrector Modes of Action Presenter: Jean Schaefer, VP of CMC & Project Management, Alzheon, Inc. About ALZ-801 Valiltramiprosate/ALZ-801 is an investigational oral agent currently in Phase 3 development as a potential first-in-class, disease-modifying treatment for Alzheimer’s disease.2-6,8,11 Valiltramiprosate is designed to inhibit the formation of neurotoxic soluble beta amyloid oligomers that contribute to cognitive decline in individuals with AD.2-6,8,13 Preclinical mechanism-of-action studies have demonstrated that ALZ-801 can completely block the formation of these neurotoxic oligomers at the dosage used in Phase 3 clinical trials.2,8,11,13 Valiltramiprosate employs an enveloping molecular mechanism of action intended to prevent the aggregation of soluble amyloid oligomers in the human brain, 13 which are associated with the onset and progression of cognitive impairment in AD patients.2,3,6,8,9 In recognition of its therapeutic promise, valiltramiprosate received Fast Track designation from the U.S. Food and Drug Administration in 2017 for the treatment of Alzheimer’s disease. Clinical trial data indicate that valiltramiprosate exhibits strong clinical efficacy at the MCI stage, and a favorable safety profile, with no observed increase in the risk of brain vasogenic edema.4-9,12,14 The initial Phase 3 program for valiltramiprosate targets Early AD patients who are homozygous for the apolipoprotein ε4 allele (APOE4/4), with plans to expand future research to include AD treatment and prevention in individuals carrying one copy of the APOE4 gene.2–9 Valiltramiprosate APOLLOE4 Phase 3 Trial An Efficacy and Safety Study of Valiltramiprosate in APOE4/4 Early Alzheimer's Disease Subjects (NCT04770220): This trial was designed to evaluate the efficacy, safety, biomarker and imaging effects of 265 mg twice daily oral dose of valiltramiprosate in Early AD subjects with two copies of the apolipoprotein ε4 allele (APOE4/4 homozygotes), who constitute approximately 15% of Alzheimer's patients. This double-blind, randomized trial compared oral valiltramiprosate to placebo treatment over 78 weeks. The APOLLOE4 trial was supported by a grant from the National Institute on Aging to Alzheon, with Susan Abushakra as the principal investigator. Valiltramiprosate APOLLOE4 Long Term Extension Trial (Phase 3 LTE) An ongoing long-term extension of the trial, APOLLOE4-LTE, evaluates valiltramiprosate in subjects who complete the core APOLLOE4 study for an additional 104 weeks of treatment for a total of 182 weeks or 3.5 years over the core and LTE study. This LTE study is currently ongoing in the US, UK, and Canada (NCT06304883). Valiltramiprosate Phase 2 Biomarker Trial Biomarker Effects of Valiltramiprosate in APOE4 Carriers with Early Alzheimer's Disease (NCT04693520): This trial was designed to evaluate the effects of 265 mg twice daily oral dose of valiltramiprosate on biomarkers of AD pathology in subjects with Early AD, who have either the APOE4/4 or APOE3/4 genotype and constitute 65-70% of Alzheimer's patients. The primary outcome was the change from baseline in plasma p-tau181. The trial also included evaluation of clinical efficacy, safety, tolerability, and pharmacokinetic profile of valiltramiprosate over 104 weeks of treatment. A completed long-term extension of the trial evaluated the same dose of valiltramiprosate for an additional 104 weeks of treatment for a total of 208 weeks.2,6,7 About Alzheon Alzheon, Inc. is a clinical-stage biopharmaceutical company dedicated to advancing a diverse portfolio of product candidates and diagnostic assays for individuals affected by Alzheimer’s disease and other neurodegenerative disorders. The company is focused on innovating therapeutic solutions that directly target the underlying pathology of neurodegeneration. Its lead Alzheimer's clinical candidate, valiltramiprosate/ALZ-801, is a first-in-class oral agent currently in Phase 3 clinical development as a potentially disease-modifying treatment for Alzheimer’s disease. Valiltramiprosate is an orally administered small molecule shown in preclinical studies to completely inhibit the formation of neurotoxic soluble amyloid oligomers. Leveraging clinical expertise and a robust technology platform, Alzheon pursues drug discovery and development using a precision medicine approach that incorporates individual genetic and biomarker profiles, aiming to advance therapies with meaningful benefits for patients. Alzheon Scientific Publications 1Abushakra S, et al: Clinical Efficacy, Safety and Imaging Effects of Oral Valiltramiprosate in APOEε4/ε4 Homozygotes with Early Alzheimer’s Disease: Results of the Phase III, Randomized, Double-Blind, Placebo-Controlled, 78-Week APOLLOE4 Trial, Drugs 2025. 2Pearson D, et al: Polymorph Analysis of ALZ-801 (Valiltramiprosate), a Valine-Conjugated Oral Prodrug of Tramiprosate in Late-Stage Clinical Development for Alzheimer’s Disease, Journal of Chemical Crystallography 2025. 3Hey JA, et al: Clinical Pharmacokinetics of Oral ALZ-801/Valiltramiprosate in a Two-Year Phase 2 Trial of APOE4 Carriers with Early Alzheimer’s Disease, Clinical Pharmacokinetics 2025. 4Aye S, et al: Point of View: Challenges in Implementation of New Immunotherapies for Alzheimer's Disease, The Journal of Prevention of Alzheimer’s Disease 2025;12(1):100022. 5Abushakra S, et al: APOLLOE4 Phase 3 Study of Oral ALZ-801/Valiltramiprosate in APOE ε4/ε4 Homozygotes with Early Alzheimer’s Disease: Trial Design and Baseline Characteristics, Alzheimer’s & Dementia 2024; 10(3): e12498. 6Tolar M, et al: The Single Toxin Origin of Alzheimer’s Disease and Other Neurodegenerative Disorders Enables Targeted Approach to Treatment and Prevention, International Journal of Molecular Sciences 2024; 25(5), 2727. 7Hey JA, et al: Analysis of Cerebrospinal Fluid, Plasma β Amyloid Biomarkers, and Cognition from a 2-Year Phase 2 Trial Evaluating Oral ALZ-801/Valiltramiprosate in APOE4 Carriers with Early Alzheimer’s Disease Using Quantitative Systems Pharmacology Model, Drugs 2024; 84(7), 825-839. 8Hey JA, et al: Effects of Oral ALZ-801/Valiltramiprosate on Plasma Biomarkers, Brain Hippocampal Volume, and Cognition: Results of 2-Year Single Arm, Open Label, Phase 2 Trial in APOE4 Carriers with Early Alzheimer’s Disease, Drugs 2024; 84(7), 811-823. 9Tolar M, et al: Neurotoxic Soluble Amyloid Oligomers Drive Alzheimer’s Pathogenesis and Represent a Clinically Validated Target for Slowing Disease Progression, International Journal of Molecular Sciences 2021; 22(12), 6355. 10Abushakra S, et al: APOE ε4/ε4 Homozygotes with Early Alzheimer’s Disease Show Accelerated Hippocampal Atrophy and Cortical Thinning that Correlates with Cognitive Decline, Alzheimer’s & Dementia 2020; 6(1): e12117. 11Tolar M, et al: Aducanumab, Gantenerumab, BAN2401, and ALZ-801—the First Wave of Amyloid-Targeting Drugs for Alzheimer’s Disease with Potential for Near Term Approval, Alzheimer’s Research & Therapy 2020; 12(1): 95. 12Tolar M, et al: The Path Forward in Alzheimer’s Disease Therapeutics: Reevaluating the Amyloid Cascade Hypothesis, Alzheimer’s & Dementia 2020; 16(11):1553-1560. 13Hey JA, et al: Discovery and Identification of an Endogenous Metabolite of Tramiprosate and Its Prodrug ALZ-801 that Inhibits Beta Amyloid Oligomer Formation in the Human Brain, CNS Drugs 2018; 32(9): 849-861. 14Hey JA, et al: Clinical Pharmacokinetics and Safety of ALZ-801, a Novel Prodrug of Tramiprosate in Development for the Treatment of Alzheimer’s Disease, Clinical Pharmacokinetics 2018; 57(3): 315-333. 15Abushakra S, et al: Clinical Effects of Tramiprosate in APOE4/4 Homozygous Patients with Mild Alzheimer’s Disease Suggest Disease Modification Potential, Journal of Prevention of Alzheimer’s Disease 2017; 4(3): 149-156. 16Kocis P, et al: Elucidating the Aβ42 Anti-Aggregation Mechanism of Action of Tramiprosate in Alzheimer’s Disease: Integrating Molecular Analytical Methods, Pharmacokinetic and Clinical Data, CNS Drugs 2017; 31(6): 495-509. 17Abushakra S, et al: Clinical Benefits of Tramiprosate in Alzheimer’s Disease Are Associated with Higher Number of APOE4 Alleles: The “APOE4 Gene-Dose Effect,” Journal of Prevention of Alzheimer’s Disease 2016; 3(4): 219-228.

Phase 2Phase 3Fast TrackClinical Result

100 Deals associated with Aducanumab-avwa

External Link

KEGG	Wiki	ATC	Drug Bank
D10541	Aducanumab-avwa	N07	DB12274

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Alzheimer Disease	United States	Biogen, Inc.	07 Jun 2021

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Cognitive Dysfunction	Phase 2	United States	Biogen, Inc.	20 Dec 2018

Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05108922 (TRAILBLAZER-ALZ 4, Pubmed \| Alzheimers Dement)	Phase 3	Alzheimer Disease amyloid plaque clearance	148	Donanemab	elkpauxsmk(tvygnqmcmc) = kzhluldkut lsnposygiw (baobbtcfqp ) View more	Positive	01 May 2025
				Aducanumab	elkpauxsmk(tvygnqmcmc) = tubkqtsvmv lsnposygiw (baobbtcfqp ) View more
NCT05310071 (ENVISION, CTgov)	Phase 3	Alzheimer Disease	1,027	Placebo (Placebo)	yxgqshdjll(helmdsixnp) = vqyiufuvlt iikghifosa (dejoskjvox, 0.408) View more	-	23 Apr 2025
				Aducanumab (Aducanumab)	yxgqshdjll(helmdsixnp) = lozdsbmnzx iikghifosa (dejoskjvox, 1.635) View more
NCT04241068 (CTgov)	Phase 3	Alzheimer Disease	1,696	Aducanumab	wkswoqrfhp = njldkqguwl cnaqscrhms (ijkoymorgm, vgwwkqikkv - azbwgfasay) View more	-	21 Feb 2025
NCT02484547 \| NCT02477800 (ENGAGE and EMERGE, Pubmed \| Neurology)	Phase 3	APOE	-	Aducanumab	mrqspzhria(lobquewdry) = slhcghzeta qzakjaqewu (lhufbpkzsa ) View more	-	13 Feb 2024
NEWS Manual	Not Applicable	Alzheimer Disease	3	聚焦超声+aducanumab	okpsraevjs(ixhtyaicts) = 6个月的联合治疗阶段，所有聚焦超声靶向脑区的血脑屏障均有开放，在手术后24-48小时内关闭， pvknnwcrhb (coswzvvahw ) View more	Positive	04 Jan 2024
				aducanumab (对侧未接受聚焦超声)
TRAILBLAZER-ALZ-4 (AAN2023)	Phase 3	Alzheimer Disease	148	Donanemab	njuarkourm(lorgnoqmhd) = 62.0% of donanemab-treated and 66.7% of aducanumab-treated participants reported an adverse event (AE), there were no serious AEs due to ARIA in donanemab arm and 1.4% serious AEs (one event) due to ARIA were reported in aducanumab arm. xfjfvunrks (emnekmrvtm )	-	25 Apr 2023
				Aducanumab
NCT02477800 (ENGAGE, AAIC2022)	Phase 3	Alzheimer Disease ApoE3/3 \| ApoE4/4	-	Aducanumab (Patient 1)	sudqduqjmh(oieikyqanc) = ttjtbcpylo ekhdehbblh (wtisnxqqlr )	-	20 Dec 2022
				Aducanumab (Patient 2)	sudqduqjmh(oieikyqanc) = pbdqounbwr ekhdehbblh (wtisnxqqlr )
NCT02484547 \| NCT02477800 (EMERGE and ENGAGE, AAN2022)	Phase 3	apolipoprotein ɛ4	2,192	Aducanumab 10 mg/kg	fquwjnsczm(owtyvmtwnb) = vdwddhwzii ftdmzmhsel (gfomrjceff ) View more	Positive	03 May 2022
				Placebo	oearygmgba(acsbyvwhbh) = lpaxkiekea xkofgiykvg (cwbuflfdfz )
EMERGE and ENGAGE (AAIC2021)	Not Applicable	apolipoprotein ε4	3,285	Aducanumab	qmqalxguvo(oztdjdgqbw) = ymmtuibgui aaweywwseq (xajadnhwbr ) View more	-	31 Dec 2021
NCT03639987 (EVOLVE, CTgov)	Phase 2	Alzheimer Disease \| Cognitive Dysfunction	52	Placebo+Aducanumab (Group 1)	qfbptcdtzc = mlfnckytmd beiixigtlx (zkdxmdgvnt, smnhbgrcsv - eefrppijks) View more	-	16 Sep 2021
				Aducanumab (Group 2)	qfbptcdtzc = twrwwwzqam beiixigtlx (zkdxmdgvnt, sumzyqtcun - aqdqnvsjzp) View more

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