Clinical Trials Show Promise For Araclon’s Vaccine, Diagnostic Test

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by Lindsey Shapiro PhD |

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ABvac40, an investigational vaccine, was safe and led to antibodies forming against the toxic amyloid-beta 40 peptide in people with Alzheimer’s disease, according to data from a Phase 2 trial.

ABvac40’s developer, Araclon Biotech, has also made progress in developing a blood test to detect Alzheimer’s in its early stages, Araclon’s lead shareholder, Grifols, reported in a press release.

Findings relating to both ABvac40 and the diagnostic test were presented at the AD/PD International Conference on Alzheimer’s and Parkinson’s Diseases 2022.

A hallmark feature of Alzheimer’s disease is the clumping together of different types of amyloid-beta protein fragments, the most abundant of which is amyloid-beta 40. These clumps can impair brain cells and cause them to die off, propelling Alzheimer’s progression.

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ABvac40 is a vaccine that targets amyloid-beta 40. It’s designed to trigger a person’s immune system to build antibodies against the toxic protein, thereby clearing existing clumps from the brain. It’s also intended to prevent new clumps from forming.

The Phase 2 trial (NCT03461276) of ABvac40 included 124 participants between the ages of 55–80, 44 of whom had very mild Alzheimer’s disease.

ABvac40 or a placebo was administered in six under-the-skin injections. The first five were given once every four weeks, and the last was given as a booster dose at week 42 (about 6 months after the last injection). The treatment’s safety, tolerability, and induction of immune responses were evaluated over 18 months (1.5 years).

Top-line results from the first part of the trial, presented in the poster “Update Phase 2 study of ABVAC40, an active vaccine anti-ab40 in patients with mild cognitive impairment or very-mild Alzheimers disease,” showed the treatment was safe, with no significant safety differences reported between the treatment and placebo groups.

Also, after receiving all six doses, patients showed a significant increase in antibodies against amyloid-beta 40, at levels greater than those observed in a previous Phase 1 trial after three doses of the treatment. These antibody levels began to drop over time after the fifth dose, but were boosted by the sixth injection.

The findings support the continuation of Part B of the study, which will use a cross-over design. In other words, participants who received a placebo in Part A will now receive ABvac40, and vice versa, for an additional 18 months. According to Grifols, that part is “progressing according to plan.”

Secondary goals of Part A, such as disease biomarkers, cognition, and quality of life, are still being evaluated.

“We are pleased to communicate these data … which confirm previous results on the safety and tolerability of ABvac40 in the early stages of Alzheimer’s disease,” Jose Terencio, Araclon’s CEO and vice president of innovation at Grifols, said.

“We are analyzing the results of the secondary variables (exploratory), related to efficacy, and we hope that ABvac40 shows its potential and lead to an innovative vaccine for patients,” Terencio said.

Araclon is also working towards developing new blood tests to detect Alzheimer’s in its early stages.

The ABtest-MS is designed to accurately quantify blood levels of two amyloid proteins — amyloid-beta 40 and 42. It’s thought that the ratio of the two proteins can predict which people have signs of amyloid buildup in the brain, an early feature of Alzheimer’s.

“This test’s predictive ability makes it ideal to detect early-stage Alzheimer’s and accelerate the recruitment for clinical trials of new treatments, reducing the screening failure rate and associated costs,” Terencio said.

The method was put to the test among 200 cognitively unimpaired people with subjective cognitive decline who participated in the Fundació ACE Healthy Brain Initiative (FACEHBI) study (EudraCT: 2014-000798-38).

In an oral presentation, titled “Plasma Aβ42/Aβ40, measured by a novel mass spectrometric method, identifies early amyloid deposition in individuals at risk of Alzheimer’s disease,” researchers showed that the ABtest-MS could predict which patients would show evidence of amyloid load in the brain at the study’s start and two years later. Data from a longer, five-year follow-up period are being analyzed, Araclon said.

Results from a multi-center study, called A4, were presented in the poster “Accurate discrimination of brain amyloid status in the multi-centric A4 study by plasma Aβ42/Aβ40 measures with a novel HPLC-MS/MS method“.

Here, researchers evaluated the test among a subset of 731 cognitively unimpaired people from sites across the U.S. and Canada. Like the other trial, ABtest-MS accurately predicted amyloid brain levels.

These and previous findings suggest the test could be used to predict Alzheimer’s progression beginning at its earliest signs.