Here’s a quick response from Gemini to my first question on Tau tangle research.
Attempts to develop drugs targeting tau tangles have been a significant part of Alzheimer's research, especially as the failures of amyloid-targeting drugs became more apparent. However, the path has been similarly challenging.
Attempts that have made it to Phase 2 or Phase 3:
* LMTM (Hydromethylthionine mesylate): This tau aggregation inhibitor developed by TauRx reached Phase 3 trials.
* Gosuranemab (BIIB092): A monoclonal antibody designed to clear tau from the brain, it advanced to Phase 2 trials.
* **Tilavonemab (ABBV-8E12): Another monoclonal antibody targeting tau, which also reached Phase 2 trials.
* Semorinemab (RO7109575): This antibody from Genentech and AC Immune made it to Phase 2.
* Tideglusib: A GSK-3ß inhibitor, which is an enzyme involved in tau phosphorylation, that went into Phase 2 trials.
* ACI-35: A vaccine targeting phosphorylated tau, which has been in Phase 2 trials.
It is difficult to provide a precise, up-to-the-minute number for all tau-specific trials as new studies are constantly being registered, initiated, or terminated. However, based on available data from scientific reviews and clinical trial registries, a number of tau-targeting drugs have reached late-stage development.
Failures between Phase 1 and Phase 3
The number of failed trials is substantial. A significant portion of the tau-targeting drugs that reached Phase 2 or 3 have ultimately failed to demonstrate clinical efficacy.
* Gosuranemab: Was terminated after a Phase 2 trial failed to show a benefit in slowing cognitive decline.
* Semorinemab: A Phase 2 trial for this drug failed to meet its primary efficacy endpoint.
* Tilavonemab: A Phase 2 trial for this drug was also stopped due to futility.
* LMTM: The Phase 3 trials for this drug failed to meet their primary endpoints.
* Tideglusib: Clinical trials were terminated after it failed to show a significant benefit.
These examples represent some of the most notable failures, but they are not exhaustive. Many other tau-related compounds, including various aggregation inhibitors, microtubule stabilizers, and other antibodies, have also been discontinued in earlier phases (Phase 1 or 2) due to a lack of efficacy, safety concerns, or futility. The experience with tau-targeting drugs is mirroring the amyloid story, where many promising candidates in preclinical studies have not translated into successful treatments for patients. |
