AXON Neuroscience has announced the results of the Phase II trial for AADvac1, its first-in-class vaccine to slow down the progression of Alzheimer's Disease.
The Phase II ADAMANT trial was designed as a randomized, double-blinded, placebo- controlled trial in mild Alzheimer's Disease. The primary objective was safety, with secondary objectives to evaluate immunogenicity, efficacy on clinical outcomes and key biomarkers. Axon studied AADvac1 on 196 patients in eight European countries over 24 months, in order to prove the concept of disease modifying effect of the vaccine and to inform the design of future confirmatory studies.
For the primary endpoint, the ADAMANT trial showed that AADvac1 has proven to be safe and well tolerated, with no difference in the incidence and nature of adverse events between the treatment and placebo groups. No other safety signals emerged from any other safety or medical assessments. This confirms the overall benign safety profile of AADvac1, demonstrated in prior clinical trials.
Axon's vaccine is an immunotherapy, harnessing the body's immune system to produce specific antibodies. In the Phase II trial, the treatment was shown to be highly effective in inducing a robust immune response, with 98.2% of patients generating antibodies against pathological tau. The finding is consistent with previous observations in the Phase I trial and support excellent immunogenicity in this population.
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A highly statistically significant impact was seen on neurodegeneration and neuronal loss, as measured in blood by Neurofilament Light Chain (NfL). It showed a marked slow-down of the expected increase of NfL in the patients treated with AADvac1, demonstrating a 12.6% change from baseline over two years versus 27.7% for patients on placebo (p value = 0.0039). This indicates that AADvac1 slows the progression of the neurodegenerative process to levels that are more typically seen in healthy individuals.
NfL is a biomarker to track and monitor effects on neurodegeneration in patients with Alzheimer's Disease, Multiple Sclerosis and other neurological disorders.
Compelling trends were observed in the reduction of three separate cerebrospinal fluid (CSF) 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.
Positive signals for cognitive endpoints were observed among younger populations in the Phase II trial. These were showed on clinical outcome measure CDR-SB and consistently further across a wide range of additional endpoints including MMSE, ADCS-MCI-ADL, MRI brain volumetry and DTI.
Clinical Dementia Rating – Sum of Boxes, Mini Mental State Examination and Activities of Daily Living are widely accepted clinical outcome measures to assess cognitive and functional decline in Alzheimer's Disease, while Magnetic Resonance Imaging and Diffusion Tensor Imaging are biomarkers that track the level of brain atrophy and damage, which are associated with the progression of the disease.
Based on the extensive learnings and positive data generated by the Phase II ADAMANT trial, Axon is moving ahead with plans for the upcoming clinical development. Axon is now seeking an experienced, global partner to help plan and conduct the next phase of clinical trials in order to rapidly bring the benefits of the therapy to a wide ranging and growing patient population.
"Today's results mark an important milestone for Axon, and for the entire population of the world that suffers from this devastating disease,” Quote from Michal Fresser, CEO of Axon Neuroscience, said. “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."