Anti-amyloid beta vaccine shows promise in Alzheimer’s trial analysis
Findings support starting higher dosing in second group of patients
A low dose of ACI-24.060, AC Immune’s investigational vaccine therapy, safely elicited the production of anti-amyloid beta antibodies among patients with Alzheimer’s disease, according to an interim analysis of a Phase 1b/2 trial.
The study, called ABATE (NCT05462106), is evaluating the vaccine’s safety and ability to provoke an immune response (immunogenicity) in adults with mild cognitive impairment associated with Alzheimer’s as well as adults with Down syndrome and signs of amyloid-beta buildup in the brain. It’s recruiting at sites in Spain and the U.K.
The findings supported starting dosing a second, higher-dose Alzheimer’s group. As planned, the trial is now screening participants with Down syndrome for its second part. Additional data from ABATE are expected in the second half of the year.
“We are delighted with the encouraging initial safety and immunogenicity findings for ACI-24.060 in ABATE,” said Andrea Pfeifer, PhD, CEO of AC Immune, in a press release. “We believe ACI-24.060’s successful development could provide patients with a novel therapeutic option offering numerous potential advantages in treatment, maintenance, and prevention settings. These early findings from ABATE represent an important step towards this goal, and we look forward to reporting more detailed data at a future conference.”
In Alzheimer’s, a toxic, misfolded form of the amyloid-beta protein forms clumps, or plaques, inside nerve cells, driving their impairment and death. Therapies that target the protein have gained substantial ground as treatments for the disease.
Two anti-amyloid antibodies are approved for Alzheimer’s disease — Leqembi (lecanemab), approved this year, and Aduhelm (aducanumab), approved since 2021. These antibodies work by binding to toxic forms of amyloid-beta and priming them for the immune system to degrade.
Vaccine elicits the body’s production of antibodies
AC Immune’s ACI-24 treatment candidates are designed to prompt the body to produce its own anti-amyloid antibodies via exposure to a small amyloid-beta fragment that has a similar shape to the misfolded version seen in Alzheimer’s.
Early formulations of ACI-24 were evaluated in three small clinical studies, where they demonstrated favorable tolerability and an ability to prompt anti-amyloid antibody production.
The company published a preclinical report last year that showed a new, optimized formulation of the vaccine was well tolerated and elicited strong immune responses against key toxic forms of the protein in mice and nonhuman primates.
ABATE is testing that optimized version — ACI-24.060 — in adults, ages 50-75, with prodromal Alzheimer’s disease, meaning they have mild cognitive impairment and signs of amyloid disease in the brain.
Participants will receive one of four ACI-24.060 doses, or a placebo, at predefined times over 48 weeks, or nearly a year. The goal is to assess treatment safety and immunogenicity, or the presence of anti-amyloid antibodies in the bloodstream, for up to 74 weeks, or nearly 1.5 years.
Results of the lowest dose showed the treatment was safe and well tolerated. The vaccine also elicited an antibody response as early as six weeks after the trial started, two weeks after the second dose was given.
PET imaging will assess amyloid plaque reductions with treatment, which can then be “benchmarked against levels of plaque clearance achieved with clinically-validated monoclonal antibodies,” said Johannes Streffer, MD, chief medical officer at AC Immune. Initial findings from that analysis are expected in 2024. Cognitive and clinical evaluations will also be explored.
Exploring vaccine’s effect on adults with Down syndrome
Along with enrolling more dosing groups to the Alzheimer’s part of the trial, a second part will enroll adults, ages 35-50, with Down syndrome who have amyloid disease in the brain.
Participants will receive an optimized dose of ACI-24.060 selected from the study’s first part or a placebo for 74 weeks, or nearly 1.5 years, and will be monitored for about two years.
Down syndrome is a genetic disease wherein patients have an extra copy of chromosome 21.
Research suggests amyloid-beta builds up in the brain of people with Down syndrome and adults with it are at an increased risk of Alzheimer’s. A number of genes that reside on chromosome 21, including the one that encodes for amyloid-beta’s precursor protein, may contribute to that risk.
“The inclusion of cohorts of participants with [Down syndrome] in the trial positions us to potentially address the needs of a vastly underserved vulnerable population, virtually all of whom will develop amyloid plaques and [Alzheimer’s],” said Streffer, who thanked the trial’s participants and investigators and added that he was looking forward to the continuation of the trial and future data.