AXON Neuroscience’s investigational AADvac1 vaccine against tau protein, a hallmark of Alzheimer’s disease, was found safe and effective at lessening signs of neurodegeneration in patients with mild Alzheimer’s, according to the results of a Phase 2 trial.
Among younger study participants, the vaccine also seemed to improve certain cognitive outcomes.
Intracellular tangles of tau protein are associated with neuronal loss and with severity of dementia. Immunotherapy using the AADvac1 vaccine is intended to induce the patient’s immune system to produce specific antibodies against abnormal forms of tau, with the ultimate goal of protecting neurons from degeneration.
The Phase 2 ADAMANT study (NCT02579252) randomized 196 patients with mild Alzheimer’s to receive ADDvac1 or a placebo. Patients were enrolled at 42 clinical centers in eight countries around Europe.
The vaccine was given in a total of 11 doses. The first six doses were administered at four-week intervals. The remaining doses were given at three-month intervals.
The trial’s main goal was to assess the vaccine’s safety. Additional goals included the vaccine’s immunogenicity (ability to produce an immune response) and effectiveness on clinical outcomes and disease biomarkers.
The results showed that AADvac1 was safe and well-tolerated, with no differences in adverse side effects between the ADDvac1-treated and placebo groups. The vaccine induced a robust immune response, with 98.2% of patients generating antibodies against toxic forms of the tau protein. These findings are in agreement with results seen in a previous Phase 1 study (NCT01850238).
Moreover, treatment with AADvac1 significantly lessened nerve cells’ death, as shown by the blood levels of neurofilament light chain (NfL). NfL is biomarker that can be measured in the blood or in the cerebrospinal fluid and reflects nerve cell damage in several neurodegenerative diseases, such as Alzheimer’s disease and multiple sclerosis.
AADvac1 treatment halted the expected increase in NfL levels in the blood: while NfL increased by 27.7% two years post-treatment (compared to the start of the trial) in the placebo group, this change was only 12.6% in patients treated with AADvac1.
These results show that AADvac1 can slow the accelerated neurodegeneration observed in Alzheimer’s disease.
“Since AADvac1 targets pathological tau, I am truly impressed by the downstream effect on neurodegeneration indicated by the neurofilament findings. This effect, observed for the very first time in an Alzheimer’s trial, is a significant and much needed boost for the industry,” Philip Scheltens, MD, PhD, said in a press release. Scheltens is director of the Alzheimer Center at the Amsterdam University Medical Center, and the chairman of the scientific advisory board of Axon.
AADvac1-treated patients also showed a trend for reduced specific Alzheimer’s disease biomarkers, including the pathogenic variants of tau protein.
The vaccine also showed positive outcomes in the Clinical Dementia Rating Scale Sum of Boxes (CDR-sb), a scale for assessing dementia severity, among the younger patient population. Additional cognitive goals that improved with AADvac1 included the Mini Mental State Examination and Activities of Daily Living questionnaire for Mild Cognitive Impairment, which measures patients’ abilities to perform daily living activities.
AADvac1 also lessen the levels of brain atrophy (shrinkage) and damage, which are associated with disease progression, as assessed by MRI and diffusion tensor imaging.
“Today’s results mark an important milestone for Axon, and for the entire population of the world that suffers from this devastating disease,” said Michal Fresser, CEO of Axon Neuroscience.
“Our vaccine is the first to solely target pathological tau proteins, which drive the cognitive decline and memory loss seen in Alzheimer’s. These results, which strongly reveal a disease-modifying effect on the disease, underpin our confidence to take the next steps in bringing a life-changing treatment to patients as soon as possible,” Fresser said.
Axon now plans continued testing AADvac1 in further clinical trials and is looking for a partner company to help plan and conduct the next trials.
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