An Alzheimer’s pill appears to protect some in a high-risk population : Shots

In April, the future of an experimental Alzheimer's drug called valiltramiprosate, or ALZ-801, looked bleak.

Researchers have just published final results study of more than 300 people aged 50 years and older who were genetically predisposed to Alzheimer's disease. Overall, those who took the drug performed no better than those who received a placebo.

But in September A. take a closer look The results showed benefits for a subgroup of 125 people who had only mild memory problems when they started taking the drug.

Those participants who were initially diagnosed with mild cognitive impairment rather than mild dementia “showed very significant responses,” said Dr. Susan Abushakra, chief medical officer of Alzheon, the drug's maker.

By one estimate, the drug slowed cognitive decline by 52% in people with mild cognitive impairment. This result appears comparable to the benefits of two Alzheimer's drugs currently on the market: lecanemab And donabemab.

But the true effect of ALZ-801 is difficult to quantify due to the relatively small number of participants in the mild cognitive impairment group.

More reliable results were obtained by measuring brain atrophy, a decline that tends to accompany Alzheimer's disease.

For example, in the hippocampus, participants who received ALZ-801 experienced approximately 18% less atrophy than those who received placebo.

This is an important distinction, Abushakra says, because the hippocampus is critical for memory and thinking.

The results were published in the journal Drugs. The study was supported by a $47 million grant from the National Institutes of Health.

A drug that is different

In general, such results are likely to fall short of the evidence required for Food and Drug Administration approval.

But ALZ-801 may receive special attention because it has potential advantages over two drugs already on the market.

Both of these drugs are monoclonal antibodies administered intravenously. This adds cost and requires patients to visit the infusion center multiple times.

ALZ-801 is a twice-daily tablet that can be taken at home.

In addition, monoclonal antibodies work primarily by destroying sticky amyloid plaques. These plaques form after pieces of a misfolded protein called beta-amyloid begin to clump together.

Alzheon's product is designed to primarily prevent plaque formation by preventing amyloid proteins from clumping together at all.

As a result, ALZ-801 does not cause swelling or bleeding in the brain that often occurs with monoclonal antibody treatments.

Safer treatment for high-risk groups

The availability of a safer drug such as ALZ-801 could be a boon for people who carry two copies of the APOE4 gene.

Their genetic status means they have about 10 times the normal risk of developing Alzheimer's disease. As a result, although APOE4/4 carriers make up only about 2% of the population, they make up about 15% of all people diagnosed with the disease.

Unfortunately, people with APOE4 genes are not only more vulnerable to Alzheimer's disease, but they are also more likely to experience side effects from monoclonal antibody treatment.

“These people are at higher risk of brain inflammation, which can be quite serious,” says Jessica LangbaumAlzheimer's disease researcher at Banner Health in Phoenix.

Despite this, Langbaum believes that people with the APOE4/4 genes can be safely treated with modern monoclonal antibodies. This may mean starting treatment at a lower dose or starting treatment earlier in the disease when less amyloid plaque is present, she said.

But David WatsonA scientist who carries two copies of the APOE4 gene believes people like him need a safer drug.

Watson, a co-author of the new study, also notes that ALZ may have benefits beyond those seen with monoclonal antibodies. For example, he says, the experimental drug is better at reducing levels of a protein fragment associated with brain cell death.

“We're really making a difference in keeping neurons alive,” he says.

New evidence of the drug's effectiveness comes from people who continued taking ALZ-801 after the end of the initial 18-month study period, Watson said.

Even though they have genes that typically cause them to decline quickly, he says, “many of them remain strong” even into their 60s and 70s.