Sage Therapeutics' experimental drug, dalzanemdor (SAGE-718), has failed to meet its primary endpoint in a Phase 2 clinical trial evaluating its efficacy in patients with mild cognitive impairment or mild dementia due to Alzheimer's disease. The study, which involved 174 participants over a 12-week treatment period, did not demonstrate a statistically significant improvement in cognition compared to placebo.
Trial Details and Outcome
The mid-stage clinical trial assessed dalzanemdor's impact on cognitive function in individuals affected by early-stage Alzheimer's. Despite the targeted approach of modulating glutamate-binding proteins on nerve cells, the drug did not yield the desired cognitive benefits. Sage Therapeutics has decided to discontinue further development of dalzanemdor for Alzheimer's disease following these results. Specific data from the trial have not been disclosed.
Broader Implications for Sage Therapeutics
This setback adds to the challenges faced by Sage Therapeutics, which has experienced a difficult period, including a significant reduction in workforce and restructuring of research programs. Earlier this year, dalzanemdor also failed in a Parkinson's disease study. According to a statement by Sage CEO Barry Greene, Alzheimer's is an "incredibly complex and devastating condition, and people with related mild cognitive impairment and mild dementia need more treatment options," and the company hopes their work will inform future research.
Dalzanemdor's Mechanism of Action
Dalzanemdor operates through a different mechanism than currently approved Alzheimer's treatments, which primarily target amyloid beta plaques. Instead, it aims to modulate the activity of glutamate, a crucial neurotransmitter involved in cognition, mood regulation, and memory formation. The drug's mechanism targets proteins on the outside of nerve cells that bind to glutamate. Given glutamate's functions, Sage has tested dalzanemdor across a variety of neurodegenerative diseases.
Market Reaction and Future Prospects
The failure in the Alzheimer's trial has further impacted Sage's stock value, which had already been under pressure. Analysts express low expectations for dalzanemdor's success in an upcoming Huntington's disease study. The company's financial position includes $647 million in cash, cash equivalents, and marketable securities as of June 30, with a net loss from operations of $211 million recorded over the first six months of the year.
