ABATE is an ongoing phase 1b/2 trial that assesses the safety, tolerability, immunogenicity, and pharmacodynamic effects of ACI-24.060 in individuals with prodromal Alzheimer disease with confirmed amyloid pathology on PET.
Initial interim results announced from the phase 1b/2 ABATE clinical trial (NCT05462106) showed that the low dose group of ACI-24.060 (AC Immune), an antiamyloid vaccine for patients with Alzheimer disease (AD), elicited a targeted response and was generally well tolerated with no safety concerns observed. As a result, dosing in ABATE’s second, higher dose AD cohort has now begun.1
In the multicenter, adaptive, placebo-controlled study, findings from the first cohort of patients with prodromal AD showed that low-dose ACI-24.060 could elicit an anti-amyloid-ß(Aß) response as soon as week 6, or 2 weeks after the second injection. Following these results, the company will also begin to screen individuals with Down syndrome (DS) for part 2 of the adaptive study.
"We are delighted with the encouraging initial safety and immunogenicity findings for ACI-24.060 in ABATE reported today. 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," Andrea Pfeifer, PhD, chief executive officer, AC Immune SA, said in a statement.1 "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."
Derived from AC Immune’s SupraAntigen platform, ACI-24.060 is designed to induce a strong polyclonal antibody response that matures and is maintained against both oligomeric and pyroglutamate-Aß species. Additionally, the agent’s is geared to enhanced the formulation of broad-spectrum protective antibodies with similar safety and tolerability previously demonstrated in the ACI-24 program in phase 1 and 2 trials.
In ABATE, the primary outcome measures were safety, as assessed through adverse events (AEs), MRI results, and physical and neurological examination. Following that, investigators will assess other outcomes such as change in anti-Aß titers, tau levels, brain amyloid levels, cognitive tests, and clinical function tests.
"ABATE’s innovative design allows us to gain crucial insights into the potential of active vaccination to halt neurodegeneration at its earliest stages,” Johannes Streffer, chief medical officer, AC Immune SA, said in a statement.1 "We expect these clinical insights will be pivotal for accelerating the development of ACI-24.060 as well as our other clinical-stage vaccine candidates targeting phosphorylated-Tau and alpha-synuclein. All of these share the convenience of patient-friendly dosing with the promise of once or twice per year administration during maintenance."
Part 1 of the study features patients aged 50 to 75 years old at screening with a diagnosis of prodromal AD, PET scan consistent with the presence of amyloid pathology, and Clinical Dementia Rating-Global score of 0.5. Patients in this cohort were not on any marketed treatment for AD or receiving a stable dose of acetylcholinesterase inhibitor and/or memantine for at least 2 months prior to baseline. Part 2 of the study features patients aged 35 to 50 years old with DS with a cytogenetic diagnosis of either trisomy 21 or complete unbalanced translocation of the chromosome 21. Furthermore, these patients also have a presence of amyloid pathology, have mild to moderate intellectual disability, and must have a study partner who has direct and regular contact with the individual for at least 10 hours per week.
The original formulation, ACI-24, showed promising results in a previously completed phase 2 study, which began in August 2018. In that study, 21 patients received injections of 1000 ug ACI-24 or placebo, 8 times over 18 months, with 6 months of follow-up. The data, presented at the 2021 Clinical Trials on Alzheimer’s Disease conference, showed that treatment with ACI-24 produced a clear immunoglobulin (IgG) antibody response, but with low IgG titers. Additionally, cerebrospinal fluid analysis showed increases in Aß40 and Aß42, suggesting target engagement; however, there was no change on amyloid-PET. Notably, no cases of amyloid-related imaging abnormalities or central nervous system inflammation were reported.