AADvac1 / Axon Neurosci - LARVOL DELTA

Progressive Supranuclear Palsy Phase 2 Platform Clinical Trial Announces the Selection of AADvac1 and AZP2006 for its First Two Regimens (ACCESSWIRE) - "The Progressive Supranuclear Palsy (PSP) Trial Platform (PTP)...has selected two promising drug candidates-Axon Neuroscience's AADvac1 and Alzprotect's AZP2006-for inclusion in the platform trial as the first two compounds to be evaluated. The trial aims to accelerate the development of effective treatments for PSP, a rare and fatal neurodegenerative disease. Additional compounds to be evaluated in the trial are expected to be announced later this year. Funded by the National Institute on Aging (NIA), part of the U.S. National Institutes of Health (NIH), the platform trial is supported by a five-year grant. Its design enables multiple therapies to be tested concurrently, establishing a perpetual, efficient and flexible path to evaluate promising drug candidates."

Clinical • Progressive Supranuclear Palsy

Post hoc analysis of ADAMANT, a phase 2 clinical trial of active tau immunotherapy with AADvac1 in patients with Alzheimer's disease, positive for plasma p-tau217. (PubMed, Alzheimers Res Ther) - P2 | "These results suggest that AADvac1 tau immunotherapy can reduce plasma biomarkers of neurodegeneration and neuroinflammation. These findings and possible observations on brain atrophy and cognition are hypothesis-generating and warrant further evaluation in a larger clinical trial."

Biomarker • Clinical • IO biomarker • Journal • P2 data • Retrospective data • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Inflammation • GFAP • Plasma NfL

Efficacy assessment of an active tau immunotherapy in Alzheimer's disease patients with amyloid and tau pathology: a post hoc analysis of the "ADAMANT" randomised, placebo-controlled, double-blind, multi-centre, phase 2 clinical trial. (PubMed, EBioMedicine) - P2 | "In the subgroup of ML imputed or CSF identified A+T+, AADvac1 slowed AD-related decline in an antibody-dependent manner. Larger anti-tau trials are warranted."

Journal • P2 data • Retrospective data • Alzheimer's Disease • CNS Disorders

Tau vaccine AADvac1 demonstrates clinical and biomarker efficacy on patients with plasma p-tau217 defined Alzheimer's disease in Phase II clinical trial: post hoc analysis (CTAD 2023) - P2 | "Tau-targeted active immunotherapy with AADvac1 showed significant treatment effects in biomarker-confirmed AD patients on cognitive and neurodegeneration-related biomarker endpoints. The response to treatment was directly related to the levels of AADvac1-induced anti-tau antibodies. These findings support a Phase IIb clinical trial on A+T+ biomarker-confirmed patients with early AD."

Biomarker • Clinical • IO biomarker • Late-breaking abstract • P2 data • Retrospective data • Alzheimer's Disease • CNS Disorders • Aβ42 • NEFL • Plasma NfL • p-tau181

"When will be release aadvac1 phase 3 results?" (@totaIcristano)

P3 data

AXON Neuroscience Presented Results from its Phase II Clinical Trial Showing Multifold Therapeutic Effect of its Vaccine-Induced Antibodies at Eurotau2021 (Yahoo Finance) - “AXON presented results from its Phase II Clinical Study for AADvac1, vaccine against Alzheimer's presented at Eurotau2021. AXON demonstrated that vaccination-induced antibodies can stop the interaction and spreading of pathological tau species and protect the brain from tau toxicity….AXON NEUROSCIENCE SE…presented results from its Phase II clinical study of its tau vaccine AADvac1 against Alzheimer's disease at the Eurotau2021 Meeting, which was being held in Lille, France on October 25-26, 2021.”

P2 data • Alzheimer's Disease • CNS Disorders

The mechanism of action and efficacy of AADvac1, an active immunotherapy against pathological tau protein, in a placebo-controlled randomised phase 2 study (AAIC 2021) - "These findings suggest that AADvac1 offers an efficacious approach to the treatment of neurofibrillary degeneration in AD with well-defined mechanism of action."

Clinical • IO biomarker • P2 data • Alzheimer's Disease • CNS Disorders • Dementia • MRI • Plasma NfL

Nature Aging publishes phase II results for AADvac1, a first-in-man Alzheimer's tau vaccine developed by Axon Neuroscience (PRNewswire) - P2, N=208; ADAMANT (NCT02579252); Sponsor: Axon Neuroscience SE; "AADvac1 demonstrates robust antibody response, excellent safety profile and highly significant impact on neurodegeneration...Evidence of clear therapeutic effect on blood neurofilament light chain protein in the whole study sample...In patients with confirmed Alzheimer's disease biomarker profile (amyloid and tau positivity) AADvac1 shows a strong efficacy signal, demonstrated by significant slowing of clinical and functional decline as measured by CDR-SB and ADCS-MCI-ADL..."

P2 data • Alzheimer's Disease • CNS Disorders

[VIRTUAL] AXON Neuroscience (BIO 2021) - "AXON Neuroscience is world’s most clinically advanced biotech in the field of Alzheimer’s disease tau therapeutics with first-in-man tau vaccine AADvac1. The company has successfully completed the preclinical phase for its lead COVID-19 asset: ACmab1 (therapeutic antibodies against COVID-19). This confirmed superior characteristics of ACmab1 vs. other therapies, in terms of efficacy on new mutated variants, method of administration, as well as its significantly lower pricing potential."

Alzheimer's Disease • CNS Disorders • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Alzheimer's disease: Recent treatment strategies. (PubMed, Eur J Pharmacol) - "Current treatment for AD (donepezil, galantamine, rivastigmine and memantine) is only symptomatic and has modest benefits...Even the positive findings presented by Biogen on Aducanumab are not entirely clear and further data is necessary to confirm its validity...Four monoclonal antibodies anti-tau (Gosuranemab, Tilavonemab, Semorinemab and Zagotenemab) and one anti-tau vaccine (AADvac1) have reached phase II, so far. In this review, we discuss the potential disease-modifying agents tested in clinical trials and update the information of drugs that are still under clinical evaluation."

Journal • Review • Alzheimer's Disease • CNS Disorders

AADvac1, an Active Immunotherapy for Alzheimer's Disease and Non Alzheimer Tauopathies: An Overview of Preclinical and Clinical Development. (PubMed, J Prev Alzheimers Dis) - "Treatment with AADvac1 proved to be remarkably safe, with injection site reactions being the only adverse event tied to treatment. AADvac1 is currently being investigated in a phase 2 study in Alzheimer's disease, and a phase 1 study in non-fluent primary progressive aphasia, a neurodegenerative disorder with a high tau pathology component."

IO Biomarker • Journal • Alzheimer's Disease • CNS Disorders

Humanized tau antibodies promote tau uptake by human microglia without any increase of inflammation. (PubMed, Acta Neuropathol Commun) - "We have previously showed that the mouse antibody DC8E8 discriminates between healthy and pathological tau, reduces tau pathology in murine tauopathy models and inhibits neuronal internalization of AD tau species in vitro.Here we show, that DC8E8 and antibodies elicited against the first-in-man tau vaccine, AADvac1, which is based on the DC8E8 epitope peptide, both promote uptake of pathological tau by mouse primary microglia. This promoting activity requires the presence of the Fc-domain of the antibodies.The IgG1 isotype of AX004 showed greater ability to promote tau uptake compared to the IgG4 isotype, while none of the antibody-tau complexes provoked increased pro-inflammatory activity of microglia. Our data suggest that IgG1 has better suitability for therapeutic development."

Journal • Immunology

Safety Study of AADvac1, a Tau Peptide-KLH-Conjugate Active Vaccine to Treat Alzheimer's Disease (clinicaltrials.gov) - P1; N=30; Completed; Sponsor: Axon Neuroscience SE; Active, not recruiting -> Completed

Trial completion • Alzheimer's Disease • Biosimilar • Reperfusion Injury

Axon's tau vaccine offers potential for treating frontotemporal dementia patients (PRNewswire) - "AXON Neuroscience announced at the 13th International Conference on Alzheimer's & Parkinson's Diseases (AD/PD2017) that the encouraging clinical trial results of...AADvac1 proved its therapeutic potential in Alzheimer's Disease and Frontotemporal Dementia (FTD)....Data from AXON's Phase I study in Alzheimer's Disease demonstrates that the antibodies elicited by vaccination with AADvac1 could recognize pathological tau protein in Alzheimer's Disease brains. This data suggests that the antibody response in patients can stop or slow down the progression of the disease."

P1 data • Alzheimer's Disease

AAdvac1: A potential vaccine for Alzheimer’s disease (Medical News) - P1, N=30; "...29 developed an IgG immune response, indicating the vaccine is very successful in promoting immune activation against pathological tau. Additionally, the vaccine had a favorable safety profile. Importantly, the cognition of the treated patients remained stable over the period of the study."

P1 data • Alzheimer's Disease

[VIRTUAL] AADVAC1 – THE FIRST TAU VACCINE FOR ALZHEIMER´S DISEASE: RESULTS FROM PHASE II STUDY (AAT-ADPD 2020) - "Conclusions This phase 2 study showed a disease-modifying effect of AADvac1 in Alzheimer’s Disease by combination of several biomarkers and clinical outcomes. The study successfully met the primary endpoint, confirming the exceptional safety profile of the vaccine, and showed its outstanding immunogenicity."

P2 data • Alzheimer's Disease • CNS Disorders • Tauopathies And Synucleinopathies • MRI • Plasma NfL

Axon presented positive phase II trial results of AADvac1 at AAT-AD/PD 2020 (PRNewswire) - P2, N=208; ADAMANT (NCT02579252); Sponsor: Axon Neuroscience SE; "AXON Neuroscience SE...presented the positive results of its Phase II trial for AADvac1, the first tau vaccine to treat and prevent Alzheimer's Disease, at the AAT-AD/PD 2020 conference....The ADAMANT Phase II trial successfully met its primary endpoint, with AADvac1 proven to be safe and well-tolerated. Further, the robust quantity and exceptional affinity of induced antibodies in more than 80% of patients confirmed the outstanding tau antibody response of AADvac1."

P2 data

AADVAC1 TAU VACCINE COMPLETING THE PHASE 2 STUDY: A PARADIGM SHIFT FOR THE AD TREATMENT HYPOTHESIS (CTAD 2019) - "The AADvac1 phase 2 study is on track to confirm the favorable safety profile and high immunogenicity, and is powered to confirm the compelling efficacy signals observed in the phase 1 Study."

P2 data

ADAMANT: 24 Months Safety and Efficacy Study of AADvac1 in Patients With Mild Alzheimer's Disease (clinicaltrials.gov) - P2; N=208; Completed; Sponsor: Axon Neuroscience SE; Active, not recruiting ➔ Completed

Trial completion

AIDA: A 24-month Phase 1 Pilot Study of AADvac1 in Patients With Non Fluent Primary Progressive Aphasia (clinicaltrials.gov) - P1; N=33; Active, not recruiting; Sponsor: Axon Neuroscience SE; Recruiting ➔ Active, not recruiting; Trial completion date: Jul 2020 ➔ Nov 2020; Trial primary completion date: Jul 2020 ➔ Nov 2020

Clinical • Enrollment closed • Trial completion date • Trial primary completion date

Searching for new hope in Alzheimer’s (pharmaphorum) - "After so many years of trial disappointments, Fresser told pharmaphorum he is cautiously optimistic about the potential of AADvac1...After the many disappointments in recent years, Fresser is hopeful that the neurological expertise within the company could create the breakthrough that pharma is looking for in Alzheimer’s."

Review

Harnessing Neuroplasticity: Modern Approaches and Clinical Future. (PubMed, Int J Neurosci) - "Compounds ranging from natural products (e.g. bilobalides, curcumin) to novel vaccines (e.g. AADvac1, RG7345) have been reported to induce long-lasting neuroplasticity in vitro and in vitro. Lastly, mechanical stimulation of brain regions through therapeutic hypothermia or deep brain stimulation (DBS) have given insight on the larger scale of neuroplasticity within the nervous system. Harnessing neuroplasticity may not only offer an arm in the vast arsenal of approaches being taken to tackle neurological disorders, such as neurodegenerative diseases, but from ample evidence, it also has major implications in neuropsychological disorders."

Clinical • Journal

Axon announces positive results from phase II ADAMANT trial for AADvac1 in Alzheimer's disease (PRNewswire) - P2, N=208; ADAMANT (NCT02579252); Sponsor: Axon Neuroscience SE; "AXON Neuroscience...today announced the results of the Phase II trial for AADvac1, its first-in-class vaccine to slow down the progression of Alzheimer's Disease...Compelling trends were observed in the reduction of three separate cerebrospinal fluid...Alzheimer's Disease specific biomarkers in treated patients, including two variants of pathological tau (phospho-Tau181 and phospho-Tau217). Despite of a smaller sample size of patients providing required lumbar punctures, the shown effect sizes were large to moderate. This strongly suggests that AADvac1 is successful in slowing the progression of tau pathology."

Biomarker • P2 data

FUNDAMANT: an interventional 72-week phase 1 follow-up study of AADvac1, an active immunotherapy against tau protein pathology in Alzheimer's disease. (PubMed, Alzheimers Res Ther) - P1; "AADvac1 displayed a benign safety profile. The evolution of IgG titres over vaccination-free periods warrants a more frequent booster dose regimen. The tendency towards slower atrophy in MRI evaluation and less of a decline in cognitive assessment in patients with high titres is encouraging. Further trials are required to expand the safety database and to establish proof of clinical efficacy of AADvac1."

Journal • P1 data

Could this Alzheimer's vaccine cut dementia cases in half (EPM Magazine) - "AADvac1 is another vaccine that stimulates the body’s immune system to attack proteins that destabilise the structure of neurons. A Phase 2 clinical trial of 185 volunteers with mild Alzheimer’s disease began in March 2015 and is expected to conclude in February 2019."

Trial completion date