What to Know About the Buzzy New Alzheimer’s Pill

4 min read

THERE’S BEEN A wave of new therapies for Alzheimer’s disease released over the last few years. But nothing would be as revolutionary as simply taking a pill to slow down cognitive decline. Better yet, the ideal medication would be a pill that could protect people with a genetic risk for Alzheimer’s.

That’s why it was such big news earlier this week when scientists reported promising trial results of a pill named valiltramiprosate or ALZ-801. Published in the journal Drugs, scientists found that when people with the apolipoprotein E ε4 (APOE ε4) allele—the strongest genetic risk factor for Alzheimer’s disease—took the pill, it slowed down decaying of the brain area involved in memory and learning.

The pill is being publicly hailed online as the next big thing in Alzheimer’s disease care. But when we spoke to neurologists who specialize in Alzheimer’s treatment, they surprisingly didn’t seem too enthusiastic about it. Here’s why.

What exactly did the study find?

The phase 3 clinical trial recruited 325 people between 50 to 80 years old with early Alzheimer’s disease with symptoms ranging from mild cognitive impairment to mild dementia. A main focus was seeing whether valiltramiprosate helped people most at risk for Alzheimer’s, ones with the APOE ε4 gene. Each person was randomly assigned to the pill or a placebo for 78 weeks.

Valiltramiprosate is designed as an anti-amyloid medication taken orally twice a day. It is intended to remove beta-amyloid plaques, a hallmark of Alzheimer’s disease, which should theoretically slow cognitive decline.

The medication showed “significant positive effects” as cognitive decline slowed by 52 percent. According to the study, that would put it on par with FDA-approved Alzheimer’s medications like lecanemab and donabemab.

People who received the pill also showed 18 percent less shrinkage in the memory center of the brain known as the hippocampus.

The most common side effects were tolerable. The worst reported events involved some nausea, vomiting, and a lowered appetite. There was also no risk of brain swelling or bleeding—a risk that is significantly higher for people with the APOE ε4 gene taking lecanemab and donabemab.

“Oral valiltramiprosate may provide a favorable benefit” for people with mild cognitive impairment, the researchers wrote in the conclusion. Sounds promising, right?

There is an important backstory here.

Rewind back to April and you’ll see some really big differences in the trial results the researchers reported then and now. Namely, valiltramiprosate didn’t work any better than those who took a placebo.

So what’s changed in the few months since the report? Did scientists tweak the formula to make it more effective?

We had neurologists take a close look at the results from then and now. Spoiler: they weren’t too impressed.

The methodology appears the same. It’s still 325 people with the APOE ε4 gene with early Alzheimer’s randomly assigned the pill or a placebo. The real difference is that months later, researchers crunched the numbers differently.

This new study took those same findings and analyzed a group of patients within it, creating different results, explains Matthew S. Schrag, MD, PhD, a vascular neurologist and an assistant professor of neurology at Vanderbilt University Medical Center. “We’ve been here before—not just in the field, but with this particular drug,” he says. “It has failed in previous clinical trials and has failed again pretty definitively in this clinical trial.”

Schrag says that the hype surrounding this medication “comes down to marketing,” adding that the “promising signals in this trial are really quite weak.”

For example, the results claim the pill can slow down cognitive decline by 52 percent. However, the actual difference isn’t as large as it seems. Schrag notes that describing things as “percent slowing” can make some data seem more notable than it actually is. “These are relative differences that can be extremely small, and still give a high percentage,” he says.

Other neurologists aren’t impressed, either.

Clifford Segil, DO, a neurologist at Providence Saint John’s Health Center, also flagged the interpretation of the 52 percent cognitive decline. “The data used by the authors to show their medication did something good noted their medication had a ‘nominally’ significant positive effects,” he says. Segil points out that “nominally” means “in name only.” While the researchers called out the 52 percent change, they also pointed out that it was nominal.

“I have never seen data presented as being nominal to result in significant positive effects in clinical practice,” Segil says.

Amit Sachdev, MD, MS, medical director in the department of neurology at Michigan State University, is also concerned that the pill makes no attempts to remove amyloid plaques already present in the brain. “Deposits already on the brain likely disrupt function. So, if you do not remove them, then it is possible to experience some ongoing dysfunction.”

Additionally, he adds that another issue is the trial length. If a 78-week trial sounds like a long time, Sachdev says that’s because many forms of Alzheimer’s disease move slowly. “This makes measuring disease activity very difficult, often requiring very long timelines,” he says. “It is also unclear how different populations will experience the drug, both good and bad.”

Ultimately, neurologists like Schrag isn’t wowed about the Alzheimer’s pill. “I would equate this to trying to read tea leaves,” he says. “They made a subgroup of a subgroup to try to demonstrate results.”

Schrag also says the data suggest there’s nothing more to investigate about valiltramiprosate. “Sometimes you have to look at what the biology is telling you,” he says. “We’ve seen a fair number of negative results. The clinical trial was convincingly negative.”