Alzheon’s Pill For Alzheimer’s Recruits for Clinical Trials

While scientists don’t know yet what causes Alzheimer’s, beta-amyloid protein plaques remain one of the prime suspects. While many approaches have focused on clearing these amyloid plaques, this strategy has not yet succeeded in bringing disease-modifying treatments to market. So far, most existing treatments for Alzheimer’s are only designed to help people manage symptoms, like memory loss. 

Valiltramiprosate, an experimental Alzheimer’s drug by Alzheon, is taking a different approach: It is designed to protect a healthy form of amyloid-beta from turning into a toxic form. The drugmakers theorize that if they can prevent this potentially protective protein from turning into neurotoxic soluble oligomers, they could prevent the damage that occurs in brains with Alzheimer’s. The ongoing APOLLOE4 trial will assess whether the experimental drug can actually slow down cognitive decline in people who carry genetic risk factors for Alzheimer’s.

Unlike the sole FDA-approved disease-modifying drug available (Aduhelm) and those close behind it in the pipeline to hopeful FDA approval (like lecanemab) — valiltramiprosate, commonly called by its investigational name ALZ-801, is taken orally. 

This means that if ALZ-801 succeeds in clinical trials and lands FDA approval, it will be easier to administer. Aduhelm and the several experimental antibody-based treatments underway all require intravenous infusions, which are harder to administer, more expensive, and less accessible. 

(In February 2024, Biogen took Aduhelm off the market indefinitely.)

Who is eligible for the APOLLOE4 Alzheimer’s trial? 

Trial centers worldwide are currently recruiting trial participants aged 50 to 80 years with progressive memory loss over the past 12 months. Candidates will be screened to see if they have two copies of a gene  that confers the highest risk for Alzheimer’s: APOE4.

So, why the focus on APOE4? Carrying two copies of this gene can increase the risk of developing Alzheimer’s by up to 12 times. APOE4 is linked to pathogenic protein deposits that disrupt brain function in Alzheimer’s as well as cardiovascular health. So, if a treatment that targets Alzheimer’s is going to work for anyone, the trial designers figure, it is most likely to work on people with the highest risk of developing Alzheimer’s. 

In studies for infused anti-amyloid drugs like Aduhelm and lecanemab, more than 20 percent of patients experienced a form of brain swelling as a side effect. So far, valiltramiprosate does not appear to cause these side effects, which require extra brain scans and monitoring. 

How does this Alzheimer’s trial work?

Since the screening procedures involve testing for genetic risk factors, it may take up to 13 weeks for a participant to learn whether they are eligible for the study. Once enrolled, they will be given the treatment or placebo to be taken twice daily, for approximately a year and a half. 

The study requires nine subsequent visits to the research center for testing. These study visits will involve procedures to check heart health, vitals, neurological and physical functions, and cognition, to establish if the drug results in substantial cognitive improvement.  

UPATED 17 October 10:53 a.m. ET: This article was corrected to update the name of the drug to the active drug, valiltramiprosate, also known as ALZ-801, rather than the prodrug, tramiprosate. According to a spokesperson for Alzheon, tramiprosate was studied in the drugmakers’ earlier programs, but it has been re-formulated for their current programs. The article was also updated to indicate that recruitment for the ongoing trials is nearly completed. The article now clarifies the drugmakers’ goal around beta-amyloid: not preventing clumping, but rather, keeping “good” beta-amyloid from turning into harmful neurotoxic soluble oligomers.

UPDATE: 3 March 2024, 9:18 P.M. ET. In February 2024, Biogen took Aduhelm off the market, citing financial concerns. Although the drug did receive accelerated, conditional FDA approval for the treatment of early Alzheimer’s disease in 2021, it is no longer available to new patients. The company announced it would sunset trials in May 2024 and cease supplying the drug to current patients in November 2024.