Sage Therapeutics Halts Dalzanemdor Development for Huntington's Disease After Phase 2 Trial Failure
Key Insights
Sage Therapeutics has stopped the development of dalzanemdor (SAGE-718) for Huntington's disease (HD) after disappointing results from the Phase 2 DIMENSION study.
The DIMENSION trial, involving 189 participants, failed to meet its clinical endpoints, showing no significant cognitive improvements with dalzanemdor compared to placebo.
Despite the setback, researchers emphasize the value of data collected for future HD drug development and understanding cognitive changes.
Sage Therapeutics has announced the discontinuation of dalzanemdor (formerly SAGE-718) development for Huntington's disease (HD) following the Phase 2 DIMENSION study's failure to meet its primary endpoints. The trial aimed to assess the drug's efficacy in improving cognitive impairment associated with HD, a critical unmet need in managing the disease.
The DIMENSION study was a 12-week, randomized, double-blind, placebo-controlled trial involving 189 participants with HD. Participants were administered dalzanemdor to evaluate its impact on cognitive function, measured by tests such as the Symbol Digit Modality Test (SDMT). The SDMT assesses attention, visual processing, working memory, and thinking speed. While dalzanemdor was generally safe and well-tolerated, results indicated no significant cognitive improvements compared to the placebo group.
"Medications targeted at cognitive changes could have a massive benefit for people with HD, such as helping them to maintain work performance and keep their jobs longer, which could expand working years for some people to defray the financial burden of HD," according to HD Buzz.
Previously, dalzanemdor had also failed to meet clinical endpoints in trials for Parkinson's and Alzheimer's diseases. These trials showed that participants taking dalzanemdor did not have meaningful differences in thinking tests compared to those on a placebo.
Despite this setback, researchers emphasize the importance of the data collected during the DIMENSION trial. The data can provide valuable insights into the cognitive changes associated with HD progression and inform the design of future clinical trials and drug development strategies. The use of cognitive assessment tools like the HD-CAB and SDMT in trials like DIMENSION demonstrates the feasibility of objectively measuring cognitive changes in HD patients.
There are over 60 companies working in the HD space right now. There are 13 clinical studies currently recruiting for HD and many more are being planned. We heard very positive clinical trial updates from four companies just this year for potential disease-modifying drugs.
While the discontinuation of dalzanemdor is disappointing for the HD community, it underscores the challenges in developing effective treatments for cognitive impairment in neurodegenerative diseases. The Huntington’s Disease (search) Society of America (HDSA) hosted a recent meeting with the US Food and Drug Administration (FDA), highlighting the urgent need for therapies addressing cognitive symptoms in HD. The HD community remains committed to supporting ongoing research efforts and advocating for the development of innovative treatments.