AADvac1 Alzheimer's Disease Vaccine
AADvac1 is a therapeutic vaccine candidate for Alzheimer's disease that targets misfolded tau protein, a common denominator of neurofibrillary pathology. The AADvac1 vaccine consists of a synthetic peptide derived from amino acids 294 to 305 of the tau sequence, i.e., KDNIKHVPGGGS, coupled to keyhole limpet hemocyanin; the precise molecular nature of the antigen has not been disclosed. In addition, AADvac1 uses aluminum hydroxide as an adjuvant.
The vaccine candidate showed several unique therapeutic features. It differs from other tau-based research by targeting the formation of pathological tau proteins and the spread of those already formed. AADvac1-induced antibodies discriminate between normal and pathological tau, ensuring only the latter are targeted. In this way, Axon's treatment is more effective and safer, says the company.
In September 2019, Axon Neuroscience published full results after a peer review (Novak et al., 2021). According to their reports, the treatment was safe and well-tolerated. Injection site reactions and transient confusion were the adverse events seen more often in the treated group compared to placebo.
The Phase II trial ADAMANT study successfully met its primary objective, with AADvac1 shown to be safe and well-tolerated. The exceptional tau antibody response demonstrated by the vaccine is critical when treating the elderly. In addition, AADvac1 significantly reduced the accumulation of Neurofilament Light Chain, an important biomarker of neurodegeneration, in the blood by 58% (p value=0.004). This was supported by substantially reduced core Alzheimer's disease cerebrospinal fluid biomarkers of tau pathology and tau neurodegeneration, including the most specific CSF biomarker, phosphotau–T217 (p value=0.009).
The company stated, 'AADvac1 is currently the most clinically-advanced tau therapy in development.' For details on AADvac1 clinical studies, see clinicaltrials.gov. AXON Neuroscience is a clinical-stage biotech company founded in 1999 with the world's largest team of researchers focused exclusively on tau-immunotherapies and tau diagnostic platforms.
AADvac1 Vaccine Indication
AADvac1 is indicated as an active immunotherapy vaccine candidate for patients with diagnosed Alzheimer's disease. It instructs the patient's immune system to produce specific antibodies targeting pathological tau. Tau proteins are vital in a brain's healthy, normal functioning. They are involved in various physiological processes, including cell signaling, the dynamics of the cellular cytoskeleton, and protecting DNA. Alzheimer's disease is triggered when these normal tau proteins become pathological by truncation, says the company.
AADvac1 Vaccine Dosage
Patients in the phase 2 study received up to 6 immunization doses.
AADvac1 Alzheimer's Disease Vaccine News
October 29, 2021 - Science Advances published the results of a study examining tau seed accumulation in Alzheimer's disease. The results suggest that from Braak stage III onward, local replication, rather than spreading between brain regions, is the primary process controlling the overall rate of tau accumulation in the neocortical areas. Furthermore, the number of seeds doubles only every five years. Thus, limiting local replication likely constitutes the most promising strategy to control tau accumulation during AD.
June 14, 2021 - Nature Aging published the results of ADAMANT, a 24-month double-blinded, parallel-arm, randomized phase 2 multicenter placebo-controlled trial of AADvac1, an active peptide vaccine designed to target pathological tau in AD.
April 3, 2020 - Vienna-based 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 AAT-AD/PD 2020 conference. AADvac1 exhibited a disease-modifying effect by significantly reducing the neurodegenerative process by 58% in comparison to the placebo arm (p value=0.004) as measured by Neurofilament Light Chain ("NfL") in the blood. NfL released in the blood and cerebrospinal fluid ("CSF") is a dynamic biomarker that reflects the extent of ongoing neurodegeneration in patients with Alzheimer's and other neurological disorders. The Phase II results indicate that AADvac1 prevents further neuronal damage in patients, maintaining levels similar to those typically observed in healthy elderly individuals. The most pronounced effects of the vaccine on clinical outcomes were observed among younger patients. In patients with young onset of Alzheimer's Disease, AADvac1 reduced the clinical decline measured by CDR-SB by 42% in comparison to the placebo arm (p value=0.062), MMSE (reduced by 31%), and ADCS-MCI-ADL (reduced by 26%). 2 Among the subgroup of younger-onset patients, the cognitive and functional effect was consistent with a significantly reduced rate of neuronal NfL accumulation in the blood by 73% in comparison to the placebo arm (p value=0.033), which represents double the effect observed in the study population as a whole.
Furthermore, MRI brain atrophy was considerably reduced in all individual brain areas associated with Alzheimer's Disease. The most substantial decrease of brain volume loss was observed in the cerebral cortex, by 47%, vs. the placebo arm (p value=0.021). This combination of clinical and biomarker outcomes demonstrates the disease-modifying effect of the AADvac1 therapy.
July 17, 2017 - AXON Neuroscience, a leader in tau research, took one further step, completing recruitment for its phase II clinical trial in Alzheimer's Disease. In total, 208 patients with mild AD were enrolled in the 24-month study, powered to evaluate the efficacy and safety of the AADvac1. With top-line data available in mid-2019, the "ADAMANT" phase II study is now the most advanced tau program in Alzheimer's research.
June 5, 2017 - AXON launches a 24-month Phase 1 Pilot Study of AADvac1 in Patients With Non-Fluent Primary Progressive Aphasia.
December 9, 2016 - The Lancet: Safety and immunogenicity of the tau vaccine AADvac1 in patients with Alzheimer's disease: a randomized, double-blind, placebo-controlled, phase 1 trial. AADvac1 had a favorable safety profile and excellent immunogenicity in this first-in-man study. However, further tests are needed to corroborate the safety assessment and to establish proof of the clinical efficacy of AADvac1.
AADvac1 Vaccine Clinical Trials
Clinical Trial NCT01850238: Safety Study of AADvac1, a Tau Peptide-KLH-Conjugate Active Vaccine to Treat Alzheimer's Disease (Completed)
AADvac1 is a candidate therapeutic vaccine for Alzheimer's disease that targets misfolded tau protein, a common denominator of neurofibrillary pathology. Based on preclinical results, the intervention is expected to reduce the number of neurofibrillary tangles, remove hyperphosphorylated tau protein, and reduce the oligomerized and insoluble pathological path tau in the brain, to halt the spread of neurofibrillary pathology through the brain, and thus prevent associated cognitive decline.
The vaccine's antigenic determinant is a synthetic peptide derived from a tau protein sequence coupled to keyhole limpet hemocyanin (KLH) and uses aluminum hydroxide (Alhydrogel) as an adjuvant. Presently, AADvac1 is intended as active immunotherapy for patients with diagnosed Alzheimer's disease (AD). Patients will receive 3 - 6 immunization doses; the raised titers of therapeutic antibodies and possible treatment benefits can extend beyond the study's duration. Because of the central role of pathological misfolded tau protein in AD's etiology, the vaccine is expected to be more effective than active or passive immunotherapies aiming to eliminate the amyloid β plaques that have been clinically investigated so far.
Clinical Trial NCT02031198: 18-month Safety Follow-up Study of AADvac1, an Active Tau Vaccine for Alzheimer's Disease (FUNDAMANT) (Completed)
AADvac1 is a candidate therapeutic vaccine for Alzheimer's disease that targets misfolded tau protein, a common denominator of neurofibrillary pathology. Based on preclinical results, the intervention is expected to reduce the number of neurofibrillary tangles, remove hyperphosphorylated tau protein, and reduce the oligomerized and insoluble pathological path tau in the brain, to halt the spread of neurofibrillary pathology through the brain, and thus prevent associated cognitive decline.
The vaccine's antigenic determinant is a synthetic peptide derived from a tau protein sequence coupled to keyhole limpet hemocyanin (KLH) and uses aluminum hydroxide (Alhydrogel) as an adjuvant. Presently, AADvac1 is intended as active immunotherapy for patients with diagnosed Alzheimer's disease (AD). However, according to need, patients will receive additional immunization doses beyond those administered in the preceding phase 1 trial; the raised titers of therapeutic antibodies and possible treatment benefits can extend beyond the study's duration.
Because of the central role of pathological misfolded tau protein in AD's etiology, the vaccine is expected to be more effective than active or passive immunotherapies aiming to eliminate the amyloid β plaques that have been clinically investigated so far.
Clinical Trial NCT02579252: 24 Months Safety and Efficacy Study of AADvac1 in Patients With Mild Alzheimer's Disease (ADAMANT) (Active).
Alzheimer's disease (AD) is a chronic progressive neurodegenerative brain disorder. Throughout the disease, pathological proteins accumulate in the brain, damaging neurons and causing them to lose connections and die.
Currently, available treatments are designed to compensate for the neurotransmitter loss caused by the disease without affecting the disease process itself.
AADvac1 is designed to raise antibodies against pathological tau protein (the primary constituent of neurofibrillary pathology in AD). These antibodies are expected to prevent tau protein from aggregating, facilitate the removal of tau protein aggregates, and prevent the spreading of pathology, slowing or halting the disease's progress.
