Alzheimer Vaccine ALZ-101 Shows Safety, Oligomer-Specific Humoral Immune Response in Early-Stage Trial

Henrik Zetterberg, MD, PhD

Data from a phase 1b trial (ALZ-C-001; NCT05328115) revealed that ALZ-101, a vaccine developed by Alzinova, was safe in patients with mild Alzheimer disease (AD) or mild cognitive impairment (MCI) due to AD. The vaccine produced an amyloid-ß oligomer-specific humoral immune response that has an impact on several biomarkers associated with disease progression, further supporting its development as a potential treatment for AD.¹

Presented at the 2024 Alzheimer’s Association International Conference (AAIC), held July 28th-August 1st in Philadelphia, Pennsylvania, the study met its primary and secondary end points of safety and tolerability over a 30-week period. In total, the data comprised of 26 eligible participants with an average Mini-Mental State Exam score of 23.9 (±0.6) and Clinical Dementia Rating-Sum of Box score of 2.9 (±1.1). In the study, patients were randomly assigned to either placebo (n = 6), 125 μg (n = 10) or 250 μg (n = 10) doses of ALZ-101 at weeks 0, 4, 8, and 16.

Led by Henrik Zetterberg, MD, PhD, a professor of neurochemistry at the University of Gothenburg, there was no cases of suspected meningoencephalitis or amyloid-related imaging abnormalities (ARIA-E). Of note, one participant had an MRI finding suggestive of an increase in size of a pre-existing microhemorrhage.

Part A of the study includes all data up to week 30. Exploratory end points including measuring cerebrospinal fluid levels of amyloid-ß, tau, neurofilament light, neurogranin, and inflammation biomarkers for which samples were collected at weeks 0 and 20. Participants who are eligible for Part B are treated with 2 doses of open-label ALZ-101, over 16 weeks and followed up during in total 68 weeks (Part A1 and B). Part A2 participants will be followed over 20 weeks.

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Additional findings from AAIC 2024 showed that treated patients had Th2 activity confirmed by antigen-recall assays on PPMCs using ELISpot. Above all, the vaccine showed immunogenic with oligomer-specific antibody titers evolving after 3 administrations. Furthermore, at week 20, the higher antibody titers observed correlated with decreases in several CSF biomarkers of AD, such as phosphorylated-tau 181, total tau, and neurogranin. In contrast, no such associations were found for neuroinflammation markers of YKL-40 and soluble triggering receptor expressed on myeloid cells 2.

In late January, Alzinova announced primary results from the full dataset of part A, confirming the favorable safety and tolerability profile observed in all dose groups. At the time, the company reported that the data showed no clear change in biomarkers and exploratory end points for cognition, possibly because of the short duration of the treatment. These outcomes are expected to be observed in the extension part of the study, which continues in 2024 with expected results in the first half of 2025.²

Because of the favorable safety and tolerability profile observed, the company applied for an addition to the study where a higher dose will be evaluated. The extension will be done as an open-label part of the study and includes 6 patients who will be treated with 400 μg over a 16-week period with 4 treatment sessions. This separate addition is not expected to affect the timetable for the planned phase 2 study.

At the time, Kristina Torfgard, chief executive officer at Alzinova, said in a statement that, "The results from the full analysis confirm that ALZ-101 is a promising vaccine candidate against Alzheimer's disease. The analysis confirms that the primary objective of safety and tolerability was met and also indicates positive results for the antibody response. We look forward to sharing our results with potential partners."

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REFERENCES
1. Zetterberg H, Rinne JO, Sandberg A, et al. Phase 1b trial on the safety, tolerability, and immunogenicity of anti-amyloid vaccine ALZ-101 in subjects with MCI or mild MCI. Presented at: AAIC; July 28-August 1, 2024; Philadelphia, PA. ABSTRACT 95440
2. Alzinova: Primary analysis confirms positive phase 1b results with ALZ-101 against Alzheimer. News release. Alzinova. January 30, 2024. Accessed July 25, 2024. https://www.alzinova.com/investors/press-releases/press/?slug=alzinova-primary-analysis-confirms-positive-phase-1b-results-with-alz-101-against-alzheimers