Araclon Biotech has provided early evidence that its Alzheimer’s disease vaccine is effective, linking the candidate to a 38% slowdown in disease progression compared to placebo in an exploratory analysis of phase 2 data.
The Spanish biotech, which is part of Grifols, reported final data from a phase 2 clinical trial of its vaccine candidate ABvac40 in a late-breaking presentation at the 2023 Clinical Trials on Alzheimer's Disease conference. Investigators randomized 134 patients with amnestic mild cognitive impairment or very mild Alzheimer’s to receive ABvac40 or placebo across a 24-month study and crossover extension.
ABvac40 “slowed disease progression up to 38% compared with placebo as measured by the Mini-Mental State Examination score,” a common way of assessing cognitive impairment. The trial wasn’t powered for finding efficacy on the score, but, in a press release, Araclon said it is encouraged by the data.
"We are pleased to report final positive results from the phase 2 study of ABvac40, including a robust immune response with some significant reduction in disease progression, all with a favorable safety profile,” Araclon CEO Jose Terencio, Ph.D., said in a statement. “The results reported for ABvac40 to date validate its clinical potential. We look forward to evaluating next steps for this program.”
ABvac40 is an active vaccine against Aβ40, a peptide found in plaques and vascular deposits that is linked to earlier onset of dementia. Work on a previous Alzheimer’s vaccine candidate, Elan Pharmaceuticals’ AN1792, stopped in phase 2 after patients developed meningoencephalitis. But Araclon has tried to step around that safety problem by eliminating the epitope recognized by T cells from its candidate.
Over the past 12 months, Araclon has begun to make the case that it has addressed the safety concerns that torpedoed AN1792, presenting top-line phase 2 data late in 2022 and following up with the findings (PDF) of a crossover extension earlier this year. No patients developed meningoencephalomyelitis or ARIA-E—brain swelling associated with other Alzheimer’s drugs—in the crossover extension. The rates of ARIA-H, a term for cerebral microhemorrhages, were similar in the vaccine and placebo group.
The final data confirm the absence of meningoencephalomyelitis or ARIA-E in recipients of the vaccine candidate. A caveat to the positive safety result is that Araclon is yet to run a trial as big as the Elan study that killed off AN1792. In that trial, 18 of the 300 immunized patients developed meningoencephalitis.