Note: This post covers both the promising ALZ-801 clinical data and practical considerations for those exploring available options today - see the final section for details.

I'm not affiliated with Alzheon and have no financial ties with Alzheon or Homotaurine of any kind. This post is based on the July 2025 AAIC session titled “Inhibition of Beta Amyloid Oligomer Neurotoxicity with Oral Valiltramiprosate.”

A Major Development That Created Hope in Our Community

The recent ALZ-801 clinical trial results have generated significant interest and hope among Phoenix members, particularly those who carry the APOE4 gene variant. For good reason: this represents a fundamental shift in how we might approach Alzheimer's treatment for high-risk individuals.

At the recent Toronto AAIC 2025, leading researchers presented data showing APOE4 carriers responding better to treatment than non-carriers (probably because we make more toxic oligomers)

Understanding Why This Matters: The Oligomer Problem

Dr. Sam Gandy from Mount Sinai explained the core issue: we've been targeting the wrong enemy. Current drugs clear visible amyloid plaques, but the real damage comes from invisible oligomers - small toxic protein clusters that directly damage brain synapses.

For APOE4 carriers, this is especially relevant because we may produce ~3x more of these toxic oligomers. Current antibody treatments often cause dangerous brain swelling (ARIA) in 40% of APOE4 carriers, making them essentially unusable for many.

The ALZ-801 Clinical Results

Dr. John Hey presented compelling data from the APOLLOE4 trial focusing on patients with mild cognitive impairment (MCI):

Cognitive Outcomes

• 52% benefit on ADAS-Cog (cognitive assessment)

  • 52% less decline than placebo

• 102% benefit on CDR-SB (functional abilities)

  • No decline on the functional endpoint

• Some patients showed no decline over 78 weeks

Translation: Patients maintained their ability to perform daily activities while placebo patients lost function.

Brain Preservation

• Preservation of brain volume, a decrease in atrophy

• Protection across all brain regions

• Strong correlation between brain preservation and cognitive benefit

• Some patients showed brain volume increase (neurogenesis?)

This is remarkable: actual brain growth in some patients considered “super responders”. Compare this to current treatments where even slowing atrophy is considered a win. The strong correlation with cognitive benefits suggests we're seeing real neuroprotection, not just symptom management.

Revolutionary Safety Profile

• Zero ARIA-E (brain swelling)

• Zero ARIA-H (microbleeds)

• Most common side effect: mild nausea

This safety profile is game-changing, especially for APOE4 carriers.
Consider that Leqembi causes ARIA-E in 20% of all patients and 40% of APOE4 carriers. Aduhelm is even worse. Some ARIA cases have been fatal. Patients need frequent MRI monitoring, and many APOE4 carriers simply can't take these drugs due to safety concerns.

Zero ARIA means APOE4 carriers can finally access treatment without fear of brain swelling or bleeding. This transforms a genetic disadvantage into a therapeutic advantage.

The Mechanism: Prevention vs. Cleanup

Dr. Kenjiro Ono's research showed ALZ-801 works differently than any current treatment:

• Prevents oligomer formation rather than clearing them

• Changes protein shape to prevent toxic clustering

• Achieves 40% brain penetration as an oral medication

• Uses 265 mg twice daily dosing

The oral delivery is revolutionary for patient quality of life.
While Leqembi and Donanemab require:

• Monthly IV infusions at specialized centers

• 1-2 hours per infusion plus travel time

• IV access challenges in elderly patients

• Significant caregiver burden

• $26,500+ annual costs

ALZ-801 offers:

• Simple twice-daily pills at home

• No infusion centers or travel

• No IV complications

• Minimal caregiver burden

• Projected to cost 70% less

For APOE4 carriers who often face decades of treatment, the difference between monthly hospital visits versus taking pills with breakfast and dinner is transformative. This isn't just about convenience - it's about sustainable, long-term treatment that people can actually maintain.

For Phoenix Members: The Current Reality

This trial has understandably created significant hope in our community. ALZ-801 is currently in Phase 3 trials with a confirmatory study planned. But what about those who don't want to (or can’t) wait?

The Homotaurine Question

ALZ-801 (valiltramiprosate) is a prodrug of homotaurine (tramiprosate), a naturally occurring compound first discovered in red algae in the 1950s. Homotaurine has been studied for decades.
It's structurally similar to the neurotransmitter GABA and was originally investigated for epilepsy before researchers discovered its anti-amyloid properties in the 1990s.

The compound gained attention when Neurochem (now Bellus Health) developed it as Alzhemed and ran large Phase 3 trials in the mid-2000s. Those trials failed, but the story didn't end there: researchers realized the issue wasn't the mechanism but the delivery.

What you need to know:

Availability :

• Homotaurine is sold OTC in several countries (Canada, Europe..)

• The FDA has effectively blocked its sale in the US (likely related to ALZ-801 patent protection)

Critical Dosing Differences:

• ALZ-801: 265 mg twice daily (as valiltramiprosate)

• Failed homotaurine trial: 100-150 mg twice daily

• The higher ALZ-801 dose may partially explain its success

Why the Original Trial Failed: The Alphase study (2011) showed homotaurine failed due to:

• Poor and inconsistent bioavailability

• High gastrointestinal side effects (nausea, vomiting, weight loss)

• Inadequate brain concentrations

• The 100-150 mg doses were likely too low

• Tested on the general population (instead of focusing on APOE4 carriers who may benefit more from ALZ-801 because we produce ~3x more toxic oligomers)

The Prodrug Advantage: ALZ-801's valyl ester modification:

• Dramatically improves absorption

• Maintains stable blood levels

• Reduces GI side effects

• Achieves therapeutic brain concentrations

This is one of the cases where pharmacodynamics are similar but pharmacokinetics make a lot of difference.

Making an Informed Decision

For those considering homotaurine:

1. Understand the limitations: The failed trial used 100-150 mg BID (twice daily). Even if you match ALZ-801's equivalent dose, you won't achieve the same bioavailability

2. Consider the math: To potentially match ALZ-801's brain levels, you might need significantly higher homotaurine doses, increasing side effects

3. Monitor carefully if exploring any intervention:

   • Track biomarkers regularly

   • Work with knowledgeable practitioners

   • Be prepared for GI side effects

4. Realistic expectations: Homotaurine ≠ ALZ-801 in effectiveness

BUT, it might be better than nothing.

This could be one of those situations where even a lower dose might produce some results, as long as the side effects are well tolerated.

The Phoenix Experiment

I'm creating a special Phoenix Experiment protocol for those interested in exploring this option. This will be directly accessible within the Phoenix Community. The protocol will include:

• Proper dosage titration strategies

• Essential tests to perform before and after

• Methods to measure if it's moving the needle

• You have to procure Homotaurine yourself (I’ll analyze and recommend brand options)

  • If you live in the US, and can’t get access to it, please read the post in our private Phoenix Community

If you are not a member yet, you can apply here.

Exciting times.

Let’s beat the odds!
-Kevin

Important Disclaimer: 
This information is for educational purposes only. Do not make any treatment decisions without consulting qualified healthcare providers.
Though I hold a Doctorate of Pharmacy, and providing medical guidance is typically central to that role, this is NOT medical advice.
My license is limited to France and select EU countries, and more importantly, this approach remains too experimental for formal recommendation.
I simply believe, as a 4/4 carrier myself, there may be potential benefits worth exploring, and that informed individuals should have access to complete information to make their own decisions.
Please carefully weigh the pros and cons, consult with your healthcare providers, and make decisions based on your individual situation and risk tolerance.