Valiltramiprosate Associated With 2.5-Year Cognitive Benefit in APOE4/4 MCI Subgroup
KEY TAKEAWAYS
- Long-term extension data from APOLLOE4 suggest sustained CDR-SB separation with valiltramiprosate in APOE4/4 participants with MCI due to early Alzheimer disease.
- Participants who received active treatment in both the core and extension periods had less CDR-SB decline than those who started treatment after placebo.
- No symptomatic ARIA events were reported in the long-term extension analysis.
Valiltramiprosate/ALZ-801 (Alzheon, Framingham, MA), an investigational oral amyloid-oligomer inhibitor, was associated with sustained clinical separation over approximately 2.5 years in APOE4/4 homozygous participants with mild cognitive impairment (MCI) due to early Alzheimer disease (AD), according to long-term extension results from the phase 3 APOLLOE4 study (NCT04770220) presented at the Alzheimer’s Association International Conference (AAIC) 2026.
The placebo-controlled APOLLOE4 core study included 325 participants with early Alzheimer disease, including 125 participants with MCI and MMSE scores ≥27. A total of 280 participants completed the 78-week core study. Participants who completed the core study could enroll in an ongoing long-term extension and receive ALZ-801 265 mg twice daily for up to 78 additional weeks.
APOLLOE4’s long-term extension included 163 participants across the United States, Canada, and the United Kingdom, including 84 who received active treatment in both the core and extension studies and 79 who received placebo in the core study followed by active treatment in the extension. Among 64 participants with MCI in the extension, 54 completed 52 weeks of ALZ-801 treatment.
In the MCI subgroup of the core study, the reported CDR-SB drug-placebo difference was approximately 0.6 points (P=.053). In the extension MCI cohort, investigators reported stabilization of CDR-SB scores at 26 and 52 weeks after an initial decline following treatment interruption between the core and extension studies. At extension week 52, the CDR-SB difference between the active-active and placebo-active groups was approximately 0.5 points, representing an estimated ALZ-801 treatment effect after about 130 weeks of nearly continuous treatment.
Treatment-emergent adverse event patterns were reported as similar to those observed in the core trial. No symptomatic amyloid-related imaging abnormalities were reported..
Source
Abushakra S, Power A, Flint S, et al. Oral valiltramiprosate shows sustained CDR-SB benefit over 2.5 years in APOE4/4 MCI subjects: APOLLOE4 phase 3 long-term extension results. Poster presented at the Alzheimer's Association International Conference (AAIC); July 12–15, 2026; London, United Kingdom, and online.