Status and rationale of selected compounds targeting various tau proteins tested in AD clinical trials
| Invested agent name | Target and Rationale | Status on clinical trial(start date–end date) | AD stage | Results | Clinical trial identifier (NCT number) |
|---|---|---|---|---|---|
| ABT-957 (Alicapistat) | Inhibition of calcium-dependent cysteine protease, calpain, which is linked to hyperphosphorylation of tau and its aggregation | Phase 1, (2014–2016) | Mild to moderate | Not reaching the effective level in CNS [25] | 02220738 |
| Semorinemab, RO7105705, RG6100 | IgG4 antibodies targeting all 6 isoforms of extracellular tau (eTau) | Phase 2, (2021) | Mild/Prodromal | The primary endpoint not met didn’t show benefit or modulation of the tau-PET signal | 03289143 |
| Phase 2, (2023) | Probable AD and moderate | Promising results on cognition | 03838747 | ||
| BIIB092,Gosuranemab | hmAB against eTau | Phase 1/2, (2018–2021) | Mild | Lack of efficacy | 03352557 |
| Zagotenemab, LY3303560 | hmAB against a conformational epitope of eTau | Phase 1/2, (2016–2021) | Mild or early symptomatic | Missed primary endpoints | 03518073 |
| RG7345,RO6426496 | Rabbit monoclonal Ab targeting phosphorylated Tau (at serine 422) | Phase 1, (2015) | Healthy males | Terminated, unfavorable phamacokinetic profile | 02281786 |
| BIIB076,NI-105 | Human recombinant monoclonal anti-tau Ab targeting mid-domain of Tau | Phase 1 (2017–2020) | Healthy and mild | Discontinued due to business reasons | 03056729 |
| AADvac1 | Active vaccine using a synthetic tau peptide | Phase 1(2013–2015)Phase 2(2016–2019) | Mild to moderate | Safe [26]and promising, but lack efficacy [27] | 0185023802579252 |
AD: Alzheimer’s disease; hmAB: human immunoglobulin monoclonal antibody