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Name: ALZ-801
Synonyms: valiltramiprosate, NRM-8499, homotaurine prodrug, 3-APS
Therapy Type: Small Molecule (timeline)
Target Type: Amyloid-Related (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Phase 3)
Company: Alzheon Inc.


This is a prodrug of homotaurine, a modified amino acid previously developed under the names tramiprosate and Alzhemed™. ALZ-801 is converted to homotaurine in vivo, but is more easily absorbed and lasts longer in the blood than tramiprosate.

Tramiprosate was reported to inhibit Aβ42 aggregation into toxic oligomers (Gervais et al., 2007; Kocis et al., 2017). Both ALZ-801 and tramiprosate are metabolized to 3-sulfopranpanoic acid (3-SPA), which is normally found in brain and also inhibits Aβ42 aggregation (Hey et al., 2018). A more recent study found that homotaurine activates GABA receptors, and suggests an alternative mechanism of action for ALZ-801 (Meera et al., 2023).

After tramiprosate failed in Phase 3, its maker, NeuroChem, marketed it as a nutritional supplement. Years later, a subgroup analysis of the trial data indicated a potential positive effect in participants who carried two copies of ApoE4 (Abushakra et al., 2016; Abushakra et al., 2017). Alzheon licensed ALZ-801 from NeuroChem and is developing it for Alzheimer’s disease.


Alzheon published results of a Phase 1 study of safety, tolerability, and pharmacokinetics of single and multiple doses of ALZ-801 in 127 healthy, old volunteers (Hey et al., 2018). The prodrug caused mild nausea and vomiting, which were not dose-related and went away after a week on drug or when taking the drug with food. Other common side effects were headaches, dizziness, and falls, also not dose-related. The drug had a longer half-life and less variability in blood levels between people than tramiprosate, and could be taken with food without affecting plasma concentrations. A dose of 265 mg of ALZ-801 twice daily achieved the same blood exposure as the 150 mg dose twice daily used in the Phase 3 tramiprosate trials, and brain levels five to 15 times higher than required to inhibit Aβ42 aggregation in vitro. 

In October 2017, the U.S. Food and Drug Administration granted ALZ-801 Fast-Track designation for the treatment of Alzheimer’s disease. 

In December 2019, Alzheon announced that its analysis of ADNI and tramiprosate trial data showed differences in cortical thickness between ApoE3/3 and ApoE4/4 carriers with mild AD, and that cortical thickness would be a secondary outcome in a planned Phase 3 trial (company press release; also see Abushakra et al., 2020). In August 2020, Alzheon announced that the U.S. National Institute on Aging will fund this trial (press release).

In September 2020, the company began a Phase 2, open-label biomarker study enrolling 84 people with early stage AD dementia and one or two copies of ApoE4. Participants receive 265 mg of drug twice daily for two years, with primary outcomes being change from baseline in CSF p-tau181 and adverse events. Secondary measures include CSF and plasma biomarkers of neurodegeneration, amyloid load, and microglial activation, plus hippocampal volume and cortical thickness MRI. The study also assesses cognition and activities of daily living. Taking place in Czechia and the Netherlands, it was expected to finish in August 2023. In February 2022, Alzheon announced interim results on 80 patients treated for six months, reporting a 29 percent reduction in plasma p-tau181 from baseline, a comparable drop in the p-tau181/Aβ42 ratio, and claiming improvement on the Rey Auditory Verbal Learning Test (press release). There was no placebo control group. The most common adverse event was mild nausea; no serious drug-related side effects were reported. In September 2022, Alzheon released 12-month data on 75 patients, announcing a 41 percent reduction in p-tau181 from baseline, and a 37 percent reduction in the p-tau181/Aβ42 ratio (press release).

The company showed more one-year data on the same trial at the December 2022 CTAD conference, including reductions in hippocampal atrophy and decline on the RAVLT compared to historical controls. Plasma Aβ40 and Aβ42, which had increased over baseline at weeks 13 and 26, dropped to below baseline. Scores on a cognition composite that had been significantly improved at week 26 were still higher than baseline but no longer significantly so. The drug continued to be safe, with no evidence of brain edema (ARIA-E). Many participants continued into a one-year open label extension. In September 2023, the company issued a press release on final study results, reporting that, at two years, plasma p-tau181 had declined by 31 percent compared to baseline, and Aβ42 had decreased by 4 percent. Hippocampal atrophy, and decline on the RAVLT and Digital Symbol Substitution Test reportedly slowed, compared to historical (ADNI) controls (press release). This study had no placebo control. The company presented trial data at the March 2024 AD/PD conference in Lisbon. After two years, the participants appeared to have benefited on most outcomes when compared to historical controls. Plasma p-tau181 was reduced at all timepoints starting at 13 weeks. While plasma Aβ42 decreased, the Aβ42/40 ratio increased slightly, by 2.4 percent. Hippocampal atrophy was 21 percent less than in matched ADNI participants. RAVLT Total and DSST scores remained above baseline at two years, and cognitive stabilization correlated significantly with lower rates of hippocampal atrophy, cortical thinning, and ventricular volume. The most common side effects were transient and mild nausea and loss of appetite. Participants are currently in their third year of extended treatment, with a fourth year starting in April 2024.

The Phase 3 trial, dubbed APOLLOE4, began in May 2021 (press release). It is enrolling 300 ApoE4 homozygotes with early to mild AD to receive 265 mg of ALZ-801 or placebo twice daily for 18 months. The primary efficacy endpoint is change in ADAS-COG; secondary endpoints include disability assessment for dementia (DAD), CDR-SB, and the Amsterdam-iADL. The trial includes as primary endpoints biomarkers of hippocampal volume MRI, and CSF and plasma measures of p-tau181. Alzheon will monitor the concentration in the CSF of Aβ oligomers, which it argues are a target of ALZ-801 (Tolar et al., 2020Tolar et al., 2021). Funded by the National Institutes on Aging and running at approximately 85 sites in the U.S., Canada, and Europe, this trial is slated to be complete by June 2024. It offers a one-year open-label extension.

For all ALZ-801 trials, see

Last Updated: 02 May 2024


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Therapeutics Citations

  1. Alzhemed™

Paper Citations

  1. . Clinical Pharmacokinetics and Safety of ALZ-801, a Novel Prodrug of Tramiprosate in Development for the Treatment of Alzheimer's Disease. Clin Pharmacokinet. 2018 Mar;57(3):315-333. PubMed.
  2. . APOE ε4/ε4 homozygotes with early Alzheimer's disease show accelerated hippocampal atrophy and cortical thinning that correlates with cognitive decline. Alzheimers Dement (N Y). 2020;6(1):e12117. Epub 2020 Dec 4 PubMed.
  3. . The path forward in Alzheimer's disease therapeutics: Reevaluating the amyloid cascade hypothesis. Alzheimers Dement. 2020 Jan 3; PubMed.
  4. . Neurotoxic Soluble Amyloid Oligomers Drive Alzheimer's Pathogenesis and Represent a Clinically Validated Target for Slowing Disease Progression. Int J Mol Sci. 2021 Jun 14;22(12) PubMed.
  5. . Targeting soluble Abeta peptide with Tramiprosate for the treatment of brain amyloidosis. Neurobiol Aging. 2007 Apr;28(4):537-47. PubMed.
  6. . Elucidating the Aβ42 Anti-Aggregation Mechanism of Action of Tramiprosate in Alzheimer's Disease: Integrating Molecular Analytical Methods, Pharmacokinetic and Clinical Data. CNS Drugs. 2017 Jun;31(6):495-509. PubMed.
  7. . Discovery and Identification of an Endogenous Metabolite of Tramiprosate and Its Prodrug ALZ-801 that Inhibits Beta Amyloid Oligomer Formation in the Human Brain. CNS Drugs. 2018 Sep;32(9):849-861. PubMed.
  8. . GABAA receptors as plausible molecular targets and mediators for taurine and homotaurine actions. Front Pharmacol. 2023;14:1271203. Epub 2023 Dec 14 PubMed.
  9. . Clinical Benefits of Tramiprosate in Alzheimer's Disease Are Associated with Higher Number of APOE4 Alleles: The "APOE4 Gene-Dose Effect". J Prev Alzheimers Dis. 2016;3(4):219-228. PubMed.
  10. . Clinical Effects of Tramiprosate in APOE4/4 Homozygous Patients with Mild Alzheimer's Disease Suggest Disease Modification Potential. J Prev Alzheimers Dis. 2017;4(3):149-156. PubMed.

External Citations

  1. company press release
  2. press release
  3. press release
  4. press release
  5. press release
  6. press release

Further Reading


  1. . Aducanumab, gantenerumab, BAN2401, and ALZ-801-the first wave of amyloid-targeting drugs for Alzheimer's disease with potential for near term approval. Alzheimers Res Ther. 2020 Aug 12;12(1):95. PubMed.
  2. . The path forward in Alzheimer's disease therapeutics: Reevaluating the amyloid cascade hypothesis. Alzheimers Dement. 2020 Jan 3; PubMed.
  3. . α-Synuclein binding activity of the plant growth promoter asterubine. Bioorg Med Chem Lett. 2022 May 15;64:128677. Epub 2022 Mar 14 PubMed.
  4. . The Single Toxin Origin of Alzheimer's Disease and Other Neurodegenerative Disorders Enables Targeted Approach to Treatment and Prevention. Int J Mol Sci. 2024 Feb 27;25(5) PubMed.