Table 2.
Small molecules inhibiting Aβ aggregation
| Name (alternative name) | Mechanism of action | Clinical phase (current status) | Pathological biomarker | Cognition | Ref |
|---|---|---|---|---|---|
| Direct inhibitors | |||||
| Tramiprosate (3APS, AlzhemedTM) | Aβ aggregation inhibitor | Phase 3 (North America, completed); Phase 3 (Europe, terminated for futility) | No data available | No benefit overall; *APOE4 homozygous overall ↑ (ADAS-Cog) *APOE4 homozygous mild AD (MMSE 22-26) ↑ (ADAS-Cog, CDR-SB, DAD) |
[82, 83] |
| ALZ-801 (Valiltramiprosate) | Valyl-prodrug of tramiprosate | Phase 3 (APOLLOE4, completed) | No data available | No benefit overall; *prespecified MCI ↑ | [85] |
| ALZT-OP1 (Cromolyn sodium+Ibuprofen) | Aβ aggregation inhibitor (cromolyn sodium)+NSAID (ibuprofen) | Phase 3 (COGNITE, completed) | No data available | No data available | [88, 89] |
| Indirect inhibitors | |||||
| Clioquinol (PBT1) | MPAC | Phase 2 (completed) | *Plasma Aβ42 ↓ | No benefit overall; *Severe subgroup (ADAS-Cog ≥25) ↑ (ADAS-Cog) |
[92, 93] |
| PBT2 | Dimethylaminomethyl-substituted clioquinol | Phase 2 (completed) | Amyloid PET overall (-); *Baseline SUVR >2.5 ↓ (Amyloid PET) Plasma Aβ (-) |
No benefit | [94, 95] |
*Asterisks indicate statistically significant differences. Arrows indicate the direction of change: for cognitive outcomes, ↑ and ↓ represent improvement or worsening, respectively; for pathological biomarkers, ↑ and ↓ indicate numerical increase or decrease. (-) indicates no change.