First Alzheimer’s pill for genetically at-risk patients shows promise in phase 3 trial

WASHINGTON, Oct 26 – Scientists have reported encouraging results from a phase 3 clinical trial of the world’s first oral Alzheimer’s pill targeting people at high genetic risk of the disease. The experimental drug, called valiltramiprosate (ALZ-801), has shown promise in slowing brain shrinkage and protecting cognitive function in early-stage patients carrying two copies of the APOE4 gene variant.

Gene link to Alzheimer’s disease

While the exact cause of Alzheimer’s disease remains unknown, genetic studies have shown that the APOE4 gene significantly increases a person’s risk. Between 15% and 25% of the population carry at least one APOE4 variant, while people with two copies—known as APOE4/4—face up to a 60% chance of developing the disease by age 85.

Dr. Susan Abushakra, chief medical officer of the U.S. biopharmaceutical firm Alzheon, explained that APOE4/4 patients make up about 15% of all Alzheimer’s cases. “These patients face the highest genetic risk, experience faster disease progression, and have the fewest treatment options,” she said. “They also have a higher risk of brain swelling and bleeding from existing anti-amyloid therapies.”

How valiltramiprosate works

Valiltramiprosate is the first investigational oral therapy designed for patients who carry two APOE4 genes. According to Dr. Abushakra, the drug works by blocking the formation of toxic amyloid clusters in the brain, which are believed to damage neurons and trigger Alzheimer’s.

“ALZ-801 works early in the process to prevent small amyloid proteins from clumping into harmful oligomers and plaques,” she said. “This mechanism protects neurons from damage and may help preserve brain tissue.”

Trial results show slower brain atrophy

The phase 3 study included 325 participants aged 50–80 with APOE4/4 at early symptomatic stages of Alzheimer’s, including mild cognitive impairment (MCI) and mild dementia. Half the participants received valiltramiprosate, while the others were given a placebo.

Researchers found that participants treated with the drug showed slower brain atrophy in multiple regions and reduced water diffusivity—a marker of slower neurodegeneration. “At the MCI stage, we observed meaningful cognitive and functional benefits along with protection against brain shrinkage,” Dr. Abushakra said.

MRI scans showed that patients receiving ALZ-801 over 78 weeks retained more brain volume than those on placebo. Using diffusion MRI, scientists also found less water in the brain tissue of treated patients, suggesting that the drug helped preserve neurons rather than merely increasing fluid.

Early treatment offers the best outcome

Although the study did not meet its primary endpoint across all participants, researchers said early-stage patients benefited the most. “Alzheimer’s is a complex, multi-stage disease, and outcomes depend on when treatment begins,” Dr. Abushakra explained.

“Patients at the mild dementia stage did not show meaningful improvement, but those treated early at the MCI stage experienced slower memory loss, stabilization of function, and protection from brain atrophy,” she added.

The findings underscore the importance of early diagnosis and intervention. Alzheon plans to build on these results in future trials and regulatory discussions.

Safer and easier to use than current treatments

Experts who reviewed the study said the pill could become a safer option for patients who cannot tolerate current Alzheimer’s drugs.

Dr. Jasdeep S. Hundal, director of The Center for Memory & Healthy Aging in New Jersey, said the results offer cautious optimism. “The treatment did not show clear benefits for all early Alzheimer’s patients, but those with very early symptoms saw slower memory decline and less brain shrinkage,” he noted.

He added that ALZ-801 appeared safe, especially compared to other drugs that cause serious side effects in genetically high-risk patients.

Ongoing search for effective memory drugs

Dr. Clifford Segil, a neurologist at Providence Saint John’s Health Center in California, emphasized the need for effective and accessible memory treatments. “We still need medications that are safe, affordable, and provide clinically meaningful results,” he said.

He added that while ALZ-801 reduced brain atrophy, it did not show significant cognitive improvement overall. Segil suggested applying modern imaging techniques from this study to assess whether existing Alzheimer’s drugs like Aricept or Namenda also offer similar structural benefits.

Looking ahead

Researchers agree that more work is needed before valiltramiprosate can be approved. However, its safety profile and targeted approach for genetically at-risk individuals represent a major step forward in Alzheimer’s treatment development.

This report was originally published by Medical News Today.