An experimental, therapeutic vaccine developed by Araclon Biotech, a Grifols Group company, targeting a peptide implicated in Alzheimer’s disease showed good safety and immunogenicity results at Phase II.
The study was not powered to test efficacy in terms of reduction in Alzheimer’s symptoms, but the company reported that individuals with early-stage Alzheimer’s who received the vaccine had a significant 38% reduction in symptoms according to the Mini-Mental State Examination score at one year although this effect did appear to wane as time went on.
The amyloid cascade hypothesis assumes that amyloid-beta accumulation in the brain starts a disease process that slowly progresses ending in full-blown Alzheimer’s disease. Several research groups and companies have developed immunotherapies that can target the amyloid-beta peptide in recent years, but clinical efficacy has yet to be proved and significant adverse events have proved problematic.
“Several isoforms of amyloid-beta are generated from sequential proteolytic cleavage of the amyloid precursor protein, including amyloid-beta 40 and amyloid-beta 42,” explain Araclon researchers in a 2018 paper describing Phase I results for the vaccine.
“Amyloid-beta 40 is the predominant variant (90%) among the secreted amyloid-beta forms, and although amyloid-beta 42 is more hydrophobic and prone to aggregate, and amyloid-beta 42 oligomers are regarded to be the most neurotoxic species, amyloid-beta 40 can also produce highly toxic diffusible aggregates, which can be prevented in vitro by specific anti-amyloid-beta 40 antibodies.”
For this reason, Araclon Biotech developed ABvac40, a vaccine targeting the C-terminal end of the amyloid-beta 40 peptide.
“Previous vaccines in development for Alzheimer’s disease faced setbacks due to harmful meningoencephalitis side effects. The results reported for ABvac40 to date validate its clinical potential, positioning it as a promising therapeutic candidate for early Alzheimer’s disease treatment,” commented Jose Terencio, Araclon CEO and vice president of Grifols Innovation and New Technologies, in a press statement about the results.
Also in the statement, the company reports that the ABvac40 vaccine met its primary endpoints and showed acceptable safety and tolerability, as well as eliciting a strong immune response in patients given the vaccine.
Overall, 134 patients were enrolled in the study with amnestic mild cognitive impairment or very mild Alzheimer’s Disease. They were randomly assigned to receive six doses of either ABvac40 or placebo over a period of 18 months. After this point patients crossed over and received the opposite of their initial treatment ie. placebo patients received ABvac40 and vice versa.
As presented at the Clinical Trials on Alzheimer’s Disease conference in Boston this week, the vaccine appeared to slow Alzheimer’s symptoms by 38% in those who received the vaccine rather than placebo at a year, but the difference in symptoms between groups had gone down at a later checkpoint at 18 and 24 months.
Terencio said the company is now “evaluating next steps for the program.” These results are promising, but more work is needed before a true assessment of the efficacy of ABvac40 can be made.