United States — Earlier this year, prospects for an experimental Alzheimer’s drug, valiltramiprosate (also known as ALZ-801), appeared uncertain after topline results from a clinical study of more than 300 adults genetically predisposed to Alzheimer’s showed no overall improvement compared to placebo. But a deeper review of the trial data, released in September, has shifted the narrative.
Researchers found that a subgroup of 125 participants who entered the trial with mild cognitive impairment—rather than mild dementia—showed notable clinical benefits after taking the drug. According to Dr. Susan Abushakra, Chief Medical Officer at Alzheon, these patients demonstrated “very meaningful responses.”
Slowing Decline and Protecting Brain Structure
Among individuals with mild cognitive impairment, ALZ-801 appeared to slow cognitive decline by 52%, a result that positions it alongside the two Alzheimer’s drugs currently authorized in the U.S.: lecanemab and donanemab. Researchers also saw more robust evidence when measuring brain atrophy, a hallmark of Alzheimer’s. Patients taking ALZ-801 experienced about 18% less shrinkage in the hippocampus, the brain region critical for memory formation and learning.
The findings, published in the journal Drugs, were supported by a $47 million National Institutes of Health grant.
How It Differs From Current Treatments
Unlike existing monoclonal antibody treatments—which require IV infusions and repeated trips to medical centers—ALZ-801 is a pill, taken at home twice daily. It also targets Alzheimer’s earlier in the disease process.
Current antibody therapies work by clearing already-formed amyloid plaques in the brain. ALZ-801 aims to prevent amyloid proteins from clumping in the first place. Because of this mechanism, the drug has not been linked to the brain swelling and bleeding—collectively known as ARIA—that have raised safety concerns in antibody-based treatments.
A Potentially Safer Option for High-Risk Patients
The drug may be particularly important for individuals who carry two copies of the APOE4 gene, making them 10 times more likely to develop Alzheimer’s. Although they represent roughly 2% of the population, these patients account for about 15% of Alzheimer’s diagnoses. They are also significantly more prone to complications from monoclonal antibody therapy.
“These individuals are at higher risk for inflammation in the brain that can be quite serious,” said Jessica Langbaum, an Alzheimer’s researcher at Banner Health in Phoenix. While Langbaum believes these patients can be treated safely with existing drugs—especially with lower doses—scientists like David Watson, himself an APOE4/4 carrier, say a safer option is urgently needed.
Watson, a co-author of the study, noted that ALZ-801 appears to better reduce toxic protein fragments associated with neuron loss. “We’re really making a difference in keeping neurons alive,” he said.
Longer-Term Results Look Encouraging
Some participants have continued taking ALZ-801 beyond the original 18-month study period. Despite their genetic risk, many are reportedly “holding their own” into their 60s and 70s, Watson added—an outcome rarely seen in APOE4/4 carriers. While the current data may not yet meet the FDA’s traditional approval threshold, the drug’s delivery advantages, safety profile, and potential prevention focus could earn it special consideration.
If future trials confirm these findings, ALZ-801 could become a practical, safer treatment option—especially for early-stage patients and those at highest genetic risk.