Dosing Starts in Phase 3 Trial of ALZ-801 in Patients With APOE[4/4] Variant

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Dosing Starts in Phase 3 Trial of ALZ-801 in Patients With APOE[4/4] Variant

Postby BrianR » Sun Jun 20, 2021 4:32 pm

This drug trial is targeted for those who are homozygous for the ε4 allele.

From Alzheimer's News Today:
A first patient has been dosed in APOLLOE4, a Phase 3 trial testing the efficacy and safety of ALZ-801, an investigational oral treatment by Alzheon ...

ALZ-801 is a small molecule designed to prevent the formation and clustering of harmful proteins that play a role in the development of Alzheimer’s. It does this by releasing tramiprosate, a compound that protects nerve cells by blocking the formation of soluble amyloid oligomers — or small protein fragments — that damage those cells and are associated with the onset of Alzheimer’s cognitive symptoms and progression.

“Because ALZ-801 is an oral treatment that has been shown to fully block formation of neurotoxic amyloid oligomers, it could be used as a monotherapy or as a long-term maintenance treatment in combination with, or following, a treatment with monoclonal antibodies, which remove amyloid plaques from the brain,” ...

This investigative treatment is for patients who carry a specific variant in the apolipoprotein E gene (APOE), linked to an earlier age of disease onset and an increased risk of rapid progression. It is thought that people with two copies of that variant, called APOE4 or APOE4/4 — estimated to be about 15% of all Alzheimer’s patients — may benefit most from an anti-amyloid therapy like ALZ-801.

APOLLOE4 (NCT04770220) aims to enroll 300 people, ages 50 to 80, with early Alzheimer’s and carrying two copies of APOE4 across about 85 sites in the U.S., Canada, and Europe. Patients will receive either 265 mg of ALZ-801 or a placebo tablet twice a day for 78 weeks (about one and a half years). More information can be found here; information on non-U.S. sites is not yet available, but may be gained by emailing ...

An ongoing Phase 2 trial of ALZ-801 (NCT04693520) is investigating the effect of treatment on the levels of Alzheimer’s-related biomarkers in people with early stage disease and one or two copies of APOE4. It main goal is to measure changes with treatment on the levels of Alzheimer’s-related biomarkers, including the proteins beta amyloid and p-tau.

“Tramiprosate, the active agent in ALZ-801, showed favorable safety in more than 3,000 patients, with no cases of vasogenic edema [swelling of blood vessels in the brain] … This profile provides an advantage over other late-stage amyloid antibodies, which are associated with increased risks of brain edema and small bleeds and are administered as intravenous infusions,” said Susan Abushakra, MD, Alzheon’s chief medical officer.

The APOLLOE4 study is being supported by a National Institute of Aging grant worth $47 million.

ALZ-801 was given fast track status by the U.S. Food and Drugs Administration (FDA) in 2017 to speed its development, potentially making it available to patients more quickly.

Relevant previous APOE4 forum threads:
Tramiprosate: a silver bullet for 4/4 carriers?
Celebration Thread! Homotaurine/Tramiprosate supplement

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Re: Dosing Starts in Phase 3 Trial of ALZ-801 in Patients With APOE[4/4] Variant

Postby NF52 » Sun Jun 20, 2021 5:59 pm

BrianR wrote:This drug trial is targeted for those who are homozygous for the ε4 allele.

From Alzheimer's News Today:
. Thanks for posting this, Brian!

This is an exciting development for several reasons:

*ALZ-801 is an oral pill, which does not require the bi-weekly or monthly infusion of IV anti-amyloid drugs including recently approved Aduhelm and others in clinical trials (BAN2401, donanemab and solanezumab)
*It has not been linked to ARIA-E or ARIA-H, the edema and micro-hemorrhages that are a risk in the IV treatments.
*According to Alzheon, the company that developed ALZ-801, it completely blocks amyloid oligomers, viewed as the most toxic form of amyloid beta, and does not focus on clearing amyloid plaques.

Here is a comparison chart of ALZ -801 with aducanumab and BAN-2401 from the Alzheon website. Click on the image to see a larger screen shot.
Clinical & Biomarkers for ALZ-801.png

The company projects a "Phase 3 AD Prevention Trial in Asymptomatic ApoE 4/4 Homozygotes" as early as this year. ALZ-801 Pipeline.
Given the approval for Aduhelm, it seems likely that they will seek to start this next trial ASAP, since it has shown strong results in earlier trials.
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4/4 and still an optimist!

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