Phase 2 LUMINARY Study of SAGE-718 in Patients with Mild Cognitive Impairment and Mild Dementia due to Alzheimer’s Disease

Sage Therapeutics presents promising results from LUMINARY Study

Data presented during the Emerging Science Session at the American Academy of Neurology’s Annual Meeting, April 2022

The LUMINARY Study is a Phase 2, open-label study evaluating the safety, tolerability and efficacy of SAGE-718 once daily in individuals with mild cognitive impairment and mild dementia due to Alzheimer’s disease

SAGE-718 demonstrated improvement across multiple tests of executive performance as well as improvement on key tests of learning and memory in the LUMINARY Study.

Sage Therapeutics, Inc., presented data from the Phase 2 LUMINARY Study that showed SAGE-718, a first-in-class, oral, positive allosteric modulator of the NMDA receptor, was generally well-tolerated and associated with improvement on multiple tests of executive performance and learning and memory in patients with mild cognitive impairment (MCI) and mild dementia due to Alzheimer’s disease (AD). The LUMINARY Study is part of CogNEXT, Sage’s early-stage trial platform designed to evaluate the therapeutic potential of SAGE-718 to treat cognitive deficits across a range of brain health disorders. The data was presented during the Emerging Science Session on Tuesday, April 5, at the 74th Annual Meeting of the American Academy of Neurology (AAN) in Seattle, US.

“Alzheimer’s disease is one of the greatest areas of unmet patient need, with an estimated global prevalence of more than 134 million people and few, if any, treatment options to specifically address mild cognitive impairment and mild dementia,” said Jim Doherty, Ph.D., Chief Development Officer at Sage.

We are encouraged by the positive results shared from the LUMINARY Study, which are consistent with signals suggesting improvement in cognitive performance seen across the SAGE-718 programme, including in people with Parkinson’s and Huntington’s disease. We look forward to learning more about the potential of SAGE-718 as we continue to advance our programme with multiple ongoing or planned Phase 2 studies.

Jim Doherty, Ph.D., Chief Development Officer at Sage

In the LUMINARY Study, a comprehensive battery of tests was used to assess multiple domains of cognitive performance in 26 patients receiving SAGE-718 3 mg once daily for 14 days. At Day 14, improvements from baseline were observed on multiple tests of executive functioning (Digit Symbol Substitution, Multitasking, One Touch Stockings, Spatial Working Memory, and 2-Back tests) and learning and memory (Pattern Recognition Memory and Verbal Recognition Memory tests).

Statistically significant improvement in the Montreal Cognitive Assessment (MoCA) (+2.3 points vs baseline) was observed at Day 28. As expected, no appreciable effect was observed on measures of simple attention/psychomotor speed, in keeping with the profile of SAGE-718 based on data to date. Functional assessments also captured notable improvement in some patients (Clinical Global Impressions Scales and Amsterdam Instrumental Activities of Daily Living Questionnaire), particularly on items measuring aspects of complex/higher order activities.

SAGE-718 was generally well-tolerated in the LUMINARY Study. Eight mild/moderate treatment-emergent adverse events (TEAE) were reported in seven patients. No serious adverse events or deaths were reported.

About the LUMINARY Study

The LUMINARY Study was an open-label, Phase 2 study evaluating SAGE-718, 3mg once daily for 14 days in patients with mild cognitive impairment and mild dementia due to AD. Patients aged 50–80 years with MoCA scores of 15-24 were included. Treatment-emergent adverse event incidence through Day 28 (primary endpoint), other safety outcomes (secondary endpoints) and cognitive and functional assessments were analysed.

About SAGE-718

SAGE-718, Sage’s first-in-class NMDA receptor PAM and lead neuropsychiatric drug candidate, is in development as a potential oral therapy for cognitive disorders associated with NMDA receptor dysfunction, potentially including Huntington’s disease, Parkinson’s disease and Alzheimer’s disease. Ongoing studies aim to evaluate whether SAGE-718 may have the potential to improve cognitive symptoms for these difficult-to-treat disorders. SAGE-718 is currently being studied in the ongoing Phase 2 DIMENSION Study, a double-blind placebo-controlled study in people with early to moderate cognitive impairment due to Huntington’s disease that is designed to evaluate the efficacy of once-daily dosed SAGE-718 over three months. Sage expects to initiate additional Phase 2 studies evaluating SAGE-718 in Huntington’s, Parkinson’s and Alzheimer’s diseases in 2022. In 2021, SAGE-718 received Fast Track Designation from the FDA for development of SAGE-718 as a potential treatment for Huntington’s disease.

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