First Alzheimer’s Pill for Genetically High-Risk Patients Shows Promise

An older woman holding a family photograph reflects the emotional impact of memory loss and ageing.

An Alzheimer’s drug for APOE4/4 patients is showing new promise in slowing early disease progression, according to results from a recent Phase 3 clinical trial. While the exact cause of Alzheimer’s disease remains unclear, research consistently shows that genetics plays a major role. One gene variant, APOE4, is strongly linked to increased Alzheimer’s risk, especially in people who inherit two copies of the gene.

Researchers estimate that 15–25% of the general population carry at least one copy of APOE4. Some people inherit two copies, known as APOE4/4, which raises their risk even further. Studies suggest that up to 60% of APOE4/4 carriers may develop Alzheimer’s disease by age 85.

People with APOE4/4 represent about 15% of all Alzheimer’s cases. They tend to experience faster disease progression and have fewer treatment options. Current anti-amyloid therapies also carry higher risks for this group, including brain swelling and brain bleeding.

A New Oral Drug Targets Early Disease Changes

A new investigational drug may offer hope for these high-risk patients. Researchers recently published Phase 3 trial results for valiltramiprosate (ALZ-801) in the journal Drugs. The study focused on people with APOE4/4 and early Alzheimer’s disease.

ALZ-801 is the first oral therapy developed specifically for genetically high-risk APOE4/4 patients. The trial included individuals with mild cognitive impairment (MCI) and mild Alzheimer’s disease dementia.

How ALZ-801 Works Differently

One of the earliest changes in Alzheimer’s disease involves the buildup of toxic amyloid protein clusters. These small clusters, called oligomers, damage neurons and later form larger amyloid plaques.

ALZ-801 targets this process early. It blocks the formation of toxic amyloid oligomers before plaques develop. By acting earlier, the drug aims to protect neurons and slow disease progression.

This approach differs from antibody treatments that remove plaques later in the disease. Those treatments can trigger side effects such as brain swelling and bleeding. ALZ-801 may avoid these risks by intervening sooner.

The APOLLOE4 Phase 3 Trial

The APOLLOE4 study was the first Phase 3 trial conducted entirely in people with two APOE4 genes. Researchers enrolled 325 participants aged 50 to 80 with early-stage Alzheimer’s disease.

Participants received either ALZ-801 or a placebo. The study followed them over 78 weeks.

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Promising Brain and Cognitive Findings

In participants with mild cognitive impairment (MCI), this Alzheimer’s drug for APOE4/4 patients slowed brain shrinkage across several key regions. Brain imaging also showed reduced water movement, a sign associated with slower neurodegeneration.

MRI scans revealed that patients treated with ALZ-801 maintained larger brain volumes than those on placebo. This difference did not result from fluid retention. Instead, it reflected better preservation of neurons and brain tissue.

Patients with MCI also experienced a meaningful slowing of memory decline, along with stabilisation of daily function. These findings suggest potential clinical benefits when treatment begins early.

Why Early Diagnosis Matters for APOE4/4 Patients

The results reinforce an important message: early diagnosis and targeted intervention make the greatest impact. Treating the right patients at the earliest symptomatic stage appears critical for success in APOE4-related Alzheimer’s disease.

Researchers plan to build on these findings in future trials. They are also continuing regulatory discussions as part of the clinical development process.

If future studies confirm these results, ALZ-801 could emerge as a safer and more accessible treatment option for APOE4/4 patients, a group that currently has very limited therapeutic choices. PRIME