An experimental oral medication called ALZ-801 (valiltramiprosate) showed promise in a phase 3 trial for slowing memory decline and reducing brain shrinkage in certain people with early Alzheimer’s disease, particularly those who carry two copies of the APOE4 gene. The study enrolled people with either mild cognitive impairment or mild dementia and tracked effects over about 18 months, comparing the pill to a placebo. While results in the entire group were not statistically decisive, a clear benefit appeared in a subgroup with the earliest symptoms. Side effects were mostly gastrointestinal, and researchers say larger, longer trials are needed to confirm these findings and define the drug’s place in care.
ALZ-801 targets amyloid formation differently than the monoclonal antibody drugs, aiming to stop plaques from forming rather than breaking them down after they appear. The trial involved 325 people aged roughly 50 to 80 who all carried the APOE4 risk gene, and participants were randomized to receive the pill twice daily or a placebo. In the full trial cohort the treatment produced modest slowing of decline, but that effect did not reach statistical significance across the entire group.
When researchers focused on the subgroup of participants with mild cognitive impairment, the results looked more encouraging. In that group ALZ-801 appeared to cut memory deterioration by about half and to halt most of the measurable daily cognitive decline. Imaging also showed less shrinkage in memory-related brain regions for people on the drug.
People taking ALZ-801 experienced roughly 18% less atrophy in the hippocampus, the brain region most linked to memory, compared with those on placebo. The main adverse effects were nausea, vomiting and reduced appetite, which were generally manageable. Importantly, the trial did not observe the brain swelling or bleeding sometimes tied to antibody infusions.
“Individuals diagnosed with MCI experience a decline in cognitive abilities, including memory, language or visual/spatial perception — however, they maintain the ability to independently perform most activities of daily living,” Christopher Weber, Ph.D., senior director of global science initiatives at the Alzheimer’s Association in Chicago, who was not part of the study, told Fox News Digital.
“In this trial, the fact that APOE-ε4/ε4 individuals did not show increased brain bleeding or swelling is encouraging, and suggests that this drug may be relatively safe in a population that is otherwise at higher risk of side effects,” Weber noted. That safety profile is an attractive feature for a pill that could be taken at home instead of receiving IV infusions. It also opens the door to thinking about earlier intervention, before plaques accumulate enough to cause damage.
“This drug can be given before the plaques fully form, so that prevention may be a goal,” Siegel, who also was not involved in the study, told Fox News Digital. Dispensing a twice-daily oral medication is far simpler than scheduling regular infusion appointments, and it could broaden access for patients who have limited mobility or who live far from infusion centers. Still, physicians will want longer follow-up and larger samples before changing standard practice.
“That said, follow-up analyses with specific subgroups were encouraging, including that the treatment did cause significant slowing of shrinkage in the hippocampus, which is a section of the brain that has a hugely important role in memory,” he told Fox News Digital. Researchers emphasize that subgroup analyses can point to where a drug might work best, but they are not a substitute for definitive, adequately powered trials. The current study’s positive signals justify further testing in bigger, longer studies focused on early disease stages and on those with APOE4-related risk.
“This treatment could potentially be used in combination with other anti-amyloid treatments, though more evidence is needed to understand how this drug could be used as a part of a combination therapy,” he said. Combining a plaque-prevention pill with other therapies that target different pathways, such as tau or inflammation, is an attractive research direction. The study was financed by the drug’s maker, Alzheon, Inc., and received support from a National Institute on Aging grant, so follow-up work is likely to involve both industry and public funding sources.
