Clinical Pharmacokinetics of Oral ALZ-801/Valiltramiprosate in a 2-Year Phase 2 Trial of APOE4 Carriers with Early Alzheimer's Disease

Topic: Drug trials: efficacy and safety

Results The steady-state plasma PK results were closely aligned with the previous 2-week PK in the ALZ-801 phase 1b study in APOE4 carrier subjects with AD, as well as a phase 1 7-day PK study in heathy elderly volunteers. The intersubject variability in plasma drug levels was low, confirming the superior performance of ALZ-801 versus oral tramiprosate tablet (150 mg BID) from the earlier tramiprosate phase 3 trials. Correlation analysis versus clinical characteristics showed that plasma exposures (Cmax and AUC8h) for ALZ-801, tramiprosate, and 3-SPA were not affected by sex, APOE genotype, age, BMI, concomitant AChEI use, or tablet lot. The inverse relationship of plasma exposures of tramiprosate and 3-SPA, but not ALZ-801, versus eGFR is consistent with renal clearance as the primary route of elimination for tramiprosate and 3-SPA (active moieties), and with the efficient conversion of ALZ-801 prodrug to the active moieties after dosing. These results demonstrate that ALZ-801 displays favorable PK properties without evidence of interactions with demographic characteristics and support its development as an oral disease-modifying treatment for AD.

Key findings

• Results The steady-state plasma PK results were closely aligned with the previous 2-week PK in the ALZ-801 phase 1b study in APOE4 carrier subjects with AD, as well as a phase 1 7-day PK study in heathy elderly volunteers.
• The intersubject variability in plasma drug levels was low, confirming the superior performance of ALZ-801 versus oral tramiprosate tablet (150 mg BID) from the earlier tramiprosate phase 3 trials.
• Correlation analysis versus clinical characteristics showed that plasma exposures (Cmax and AUC8h) for ALZ-801, tramiprosate, and 3-SPA were not affected by sex, APOE genotype, age, BMI, concomitant AChEI use, or tablet lot.
• The inverse relationship of plasma exposures of tramiprosate and 3-SPA, but not ALZ-801, versus eGFR is consistent with renal clearance as the primary route of elimination for tramiprosate and 3-SPA (active moieties), and with the efficient conversion of ALZ-801 prodrug to the active moieties after dosing.
• These results demonstrate that ALZ-801 displays favorable PK properties without evidence of interactions with demographic characteristics and support its development as an oral disease-modifying treatment for AD.

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Study details

• Study designlongitudinal study
• Participants24
• Evidence strengthModerate

Read the original

• DOI: 10.1007/s40262-025-01482-8
• PubMed: 39907966
• Original source →

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@article{hey2025-39907966,
  author  = {Hey, J. A. and Yu, J. Y. and Abushakra, S. and Schaefer, J. F. and Power, A. and Kesslak, P. and Paul, J. and Tolar, M.},
  title   = {{Clinical Pharmacokinetics of Oral ALZ-801/Valiltramiprosate in a 2-Year Phase 2 Trial of APOE4 Carriers with Early Alzheimer's Disease}},
  journal = {Clinical pharmacokinetics},
  year    = {2025},
  doi     = {10.1007/s40262-025-01482-8},
  pmid    = {39907966},
  url     = {https://doi.org/10.1007/s40262-025-01482-8}
}

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