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 involving 189 patients. Participants were randomized to evaluate the safety and efficacy of dalzanemdor in addressing cognitive deficits linked to Huntington's disease. The primary endpoint was the change from baseline on the Symbol Digit Modalities Test (SDMT) at day 84. The results indicated no statistically significant difference between patients treated with dalzanemdor and those receiving a placebo.
Analyses of secondary endpoints also failed to demonstrate statistically significant or clinically meaningful differences between the two treatment groups. Despite the lack of efficacy, the study indicated that dalzanemdor was generally well-tolerated, with most treatment-emergent adverse events being mild to moderate in severity, and no new safety signals were observed.
"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. "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."
Huntington's disease is a genetic, 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. Experts anticipate an increase in diagnoses due to improved detection and demographic shifts.
The termination of the dalzanemdor program follows a series of mid-stage failures for Sage, along with a recent restructuring that involved halving its R&D team. This restructuring occurred after the company's depression drug, Zurzuvae, received approval only for postpartum treatment, limiting its market reach.
