Sage Therapeutics has ceased the development of dalzanemdor (SAGE-718) for Huntington's disease following disappointing results from the Phase II DIMENSION study. The company announced Wednesday that the drug, an investigational allosteric NMDA receptor modulator, failed to demonstrate a statistically significant improvement in cognitive function in adult patients with Huntington's disease.
The DIMENSION study evaluated the efficacy of dalzanemdor over 84 days but did not achieve its primary endpoint, which was a statistically significant improvement from baseline in the Symbol Digit Modalities Test (SDMT). The SDMT is a validated tool for measuring sustained attention, processing speed, visual scanning, and motor speed. Furthermore, the treatment did not show statistically significant or clinically meaningful benefits in secondary endpoints.
Impact on Clinical Programs
As a result of this setback, Sage Therapeutics will also discontinue the ongoing open-label PURVIEW study, which was primarily designed to assess the long-term safety of dalzanemdor in patients with Huntington's disease. This decision marks another setback for the drug, which had previously failed to show efficacy in clinical trials for Parkinson's and Alzheimer's diseases.
CEO Barry Greene expressed his disappointment in a statement, acknowledging the unmet need for new treatment options for Huntington's disease. "We are disappointed by these findings, especially for the individuals and families affected by Huntington’s Disease who have long awaited new treatment options."
Previous Trial Data and Analyst Perspectives
Earlier data from June 2024 showed that dalzanemdor had a slight improvement over placebo in cognition for Huntington's disease patients, but analysts considered the results underwhelming. William Blair analysts noted that the small numerical changes did not provide definitive evidence of the drug's activity.
Dalzanemdor's Troubled Clinical History
Dalzanemdor's clinical development has faced multiple challenges. In April 2024, a Phase II trial for Parkinson's disease was halted after the drug failed to significantly improve scores on the Wechsler Adult Intelligence Scale Fourth Edition-IV Coding Test at 42 days. Similarly, in October 2024, a Phase II study for Alzheimer's disease showed no significant cognitive improvements compared to placebo, leading to the termination of its development for that indication as well.
Strategic Implications for Sage
Stifel analyst Paul Matteis suggested that discontinuing the Huntington's program could free up capital for Sage. The company recently implemented a cost-cutting initiative, laying off approximately 33% of its workforce, including over half of its R&D staff. Matteis noted that with the launch of the postpartum depression drug Zurzuvae underway, the focus shifts to Sage's future strategic direction.
