Huntington’s Disease Clinical Trials: Updates on Dalzanemdor and Tominersen

1. Dalzanemdor (SAGE-718):
- An oral NMDA receptor positive allosteric modulator (PAM) designed to improve cognitive function in Huntington's disease.
- Currently in Phase 2 studies, including SURVEYOR and DIMENSION, which are evaluating its efficacy in patients with mild to moderate cognitive impairment.
- The drug aims to boost NMDA receptor activity, which is believed to be impaired in Huntington's patients, leading to cognitive decline.
2. Tominersen:
- An RNA-based therapy administered into the spinal canal to reduce levels of both normal and mutated forms of the huntingtin protein.
- Currently in Phase 3 trials, including GENERATION HD1, which tested the drug against a placebo in 791 adults with Huntington's disease.
3. Phase 3 Trials:
- The GENERATION HD1 trial showed that tominersen effectively lowered abnormal huntingtin levels but did not demonstrate significant clinical benefits.
- Another Phase 3 trial, PURVIEW, is evaluating the long-term safety and exploratory efficacy of dalzanemdor in Huntington's patients.
4. Recent Updates:
- Sage Therapeutics announced that dalzanemdor did not show statistically significant differences versus placebo in the Phase 2 PRECEDENT study for mild cognitive impairment in Parkinson's disease.
- The company is expected to report topline data from the SURVEYOR and DIMENSION studies in Huntington's disease later in 2024.
5. Future Directions:
- Sage Therapeutics is advancing its clinical program for dalzanemdor, focusing on its potential lead indication in Huntington's disease and cognitive impairment in Alzheimer's disease.
- The company plans to report topline data from the LIGHTWAVE study in Alzheimer's disease later in 2024.