Shares of Sage Therapeutics, Inc. SAGE were down 4.3% on Oct. 8 after the company announced disappointing top-line data from the phase II LIGHTWAVE study, which evaluated its neuropsychiatric candidate, dalzanemdor (SAGE-718) for treating mild cognitive impairment (MCI) and mild dementia in Alzheimer’s Disease (AD). The stock continued to lose another 2.8% in the after-market hours.

The double-blind, placebo-controlled LIGHTWAVE study evaluated the effects of dalzanemdor in participants with MCI or mild dementia due to AD.

Data from the study showed that treatment with dalzanemdor failed to demonstrate a statistically significant difference from baseline as compared to placebo on the Wechsler Adult Intelligence Scale Fourth Edition (WAIS-IV) Coding Test score at day 84. This was the primary endpoint of the 12-week LIGHTWAVE study.

Year to date, shares of Sage Therapeutics have plunged 70.3% compared with the industry’s decline of 5.2%.

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Per management, the analyses of data from the LIGHTWAVE study also did not indicate any meaningful differences versus placebo in the other exploratory endpoints, such as RBANS total score or MoCA total score. Treatment with dalzanemdor was generally well-tolerated and no new safety signals were reported.

Following the disappointing data from the LIGHTWAVE study, SAGE decided to stop further development of dalzanemdor in AD.

SAGE's Earlier Setback in Parkinson's Study

In April 2024, Sage Therapeutics reported top-line data from the phase II PRECEDENT study, which investigated dalzanemdor in patients with MCI associated with Parkinson’s disease (PD).

The study failed to achieve its primary endpoint of demonstrating a statistically significant difference from baseline in participants treated with dalzanemdor compared to placebo. Per the company, the analyses of data also did not indicate any meaningful differences versus placebo in the other exploratory endpoints, such as SCOPA-Cog.

Back then, management also pointed out that more than half of the total study participants experienced treatment-emergent adverse events (TEAEs) ranging from mild to moderate in severity.

Based on these results, SAGE decided not to pursue the development of dalzanemdor in PD indication.

SAGE's Other Study on Dalzanemdor

Dalzanemdor is currently being evaluated as a potential treatment for patients with cognition dysfunction associated with Huntington’s disease (HD) across three ongoing clinical studies – two phase II studies (DIMENSION and SURVEYOR) and a phase III study (PURVIEW).