Sage Therapeutics has ceased the development of dalzanemdor (SAGE-718) following the failure of its Phase II DIMENSION study. The trial, designed to assess the drug's efficacy in treating cognitive impairment associated with Huntington's disease, did not meet its primary or secondary endpoints.
The DIMENSION study was a 12-week, double-blind, placebo-controlled trial that randomized 189 patients to evaluate the safety and efficacy of dalzanemdor. The primary endpoint was the change from baseline on the Symbol Digit Modalities Test (SDMT) at day 84. Results indicated no statistically significant difference between patients receiving dalzanemdor and those on placebo. Further analysis of secondary endpoints also failed to demonstrate significant or clinically meaningful differences between the treatment groups.
"We are disappointed by the results of the DIMENSION study, especially for the individuals and families affected by Huntington’s Disease who have long awaited new treatment options," said Sage CEO Barry Greene. He added, "Innovation is desperately needed, and we are immensely grateful to the participants, investigators, and the entire Huntington’s disease community whose unwavering commitment to advancing research helped make this study possible."
While the drug was generally well-tolerated with mostly mild to moderate adverse events, the lack of efficacy led to the decision to halt further development and close the PURVIEW open-label safety study. This setback follows a series of mid-stage failures for Sage and a recent restructuring that included halving its R&D team. The company also faced challenges with its depression drug Zurzuvae, which was approved only for postpartum treatment, limiting its market reach.
Huntington's disease is a progressive, neurodegenerative disorder characterized by involuntary muscle movements and cognitive decline. The global prevalence is estimated at 2.71 per 100,000 individuals, with Northern European populations showing the highest rates. Epidemiologists project an increase in Huntington's disease diagnoses due to improved detection and demographic shifts.
