Dalzanemdor halted for Alzheimer’s; fails to boost cognitive function
LIGHTWAVE study falls short of main goal of improving cognition
Sage Therapeutics plans to stop developing dalzanemdor (SAGE-718) for Alzheimer’s disease after the treatment failed to meet the main goal of improving cognitive function in a Phase 2 study in patients with mild cognitive impairment or mild dementia.
In the LIGHTWAVE study (NCT05619692), patients treated with dalzanemdor didn’t show significant improvement in cognitive function, as measured by the Wechsler Adult Intelligence Scale Fourth Edition (WAIS-IV) Coding Test, compared with those on a placebo, though the treatment was shown to be safe and well tolerated.
“While we are disappointed by the results of the LIGHTWAVE Study, we are grateful to participants, investigators, care partners, patient advocates and the Alzheimer’s community who helped make this important research possible,” Sage CEO Barry Greene said in a company press release.
Dalzanemdor is an oral molecule that increases the activity of the brain’s N-methyl-D-aspartate (NMDA) receptors, which are essential for nerve cell communication. Researchers believe that signaling from the NMDA receptor may be impaired in Alzheimer’s, contributing to cognitive decline.
Need to boost cognitive function
A small Phase 2 open-label study called LUMINARY (NCT04602624), which involved 26 patients with mild cognitive impairment or mild dementia due to Alzheimer’s, showed improved learning, memory, and executive function after two weeks of daily treatment with dalzanemdor. However, the study lacked a placebo control.
The LIGHTWAVE study included a larger number of patients — a total of 174 — with mild cognitive impairment or mild dementia due to Alzheimer’s, ages 50-80, who were randomly assigned to receive a soft gelatin capsule containing either dalzanemdor or a placebo every day for 12 weeks.
The goal was to assess changes in cognitive function, as measured by the WAIS-IV, a paper-and-pen test that involves matching symbols to numbers, after 12 weeks. No significant differences were found between patients on dalzanemdor versus the placebo.
While dalzanemdor didn’t outperform the placebo in exploratory measures of cognitive function, it was generally well tolerated, and no new safety concerns were identified. Most of the side effects reported during the study were mild to moderate.
“Alzheimer’s [disease] is an incredibly complex and devastating condition, and people with related mild cognitive impairment and mild dementia need more treatment options,” Greene said. “We hope our work and these findings help to inform future research.”
Sage is also testing dalzanemdor in Huntington’s disease, and plans to release top-line data from a Phase 2 study, DIMENSION (NCT05107128), later this year. In Parkinson’s disease, dalzanemdor’s clinical development was discontinued after it failed to outperform a placebo in improving cognitive function in another Phase 2 study.
About the Author
