Neumora's Alzheimer's disease agitation drug shows early Phase Ib success

Neumora reported that its oral drug NMRA-511 reduced agitation on the Cohen-Mansfield Agitation Inventory in a Phase Ib trial, with larger effects in a subgroup with elevated anxiety; the company plans further studies including a multiple ascending dose extension in 2026.

Neumora Therapeutics reported that its oral drug NMRA-511 reduced agitation in a Phase Ib trial of people with Alzheimer's disease. The trial used the Cohen-Mansfield Agitation Inventory (CMAI) to measure agitation. Neumora described NMRA-511 as a selective vasopressin 1a receptor (V1aR) antagonist that is brain-penetrant and orally administered. The company reported a favorable tolerability and safety profile in the study, with no reports of somnolence or sedation. Key findings: - In the modified analysis set of 71 patients treated twice daily, NMRA-511 produced placebo-adjusted CMAI reductions of 2.6 points at week six and 2.1 points at week eight. - In the subgroup of 36 patients with elevated anxiety, placebo-adjusted CMAI reductions were 7.6 points at week six and 5.6 points at week eight. - The CMAI assesses the frequency of 29 specific agitated or aggressive behaviours in older adults with dementia. - NMRA-511 was reported as an oral, highly potent, brain-penetrant selective V1aR antagonist with a favorable tolerability and safety profile and no reported somnolence or sedation in the study. - Based on the Phase Ib data, Neumora plans a multiple ascending dose (MAD) extension study in 2026 and later intends to initiate a Phase II/III dose-ranging trial, and it is also working on a once-daily formulation for 2026. Summary: Phase Ib results reported that NMRA-511 reduced agitation scores on the CMAI and was described as well tolerated in the trial. Neumora plans further clinical testing in 2026, including a MAD extension and a subsequent Phase II/III dose-ranging study. Other treatments in the field include Otsuka's Rexulti, the only drug approved for Alzheimer's disease agitation, and investigational candidates such as AXS-05, which is awaiting an FDA decision.