Biglan K, Munsie L, Svensson KA, et al. - In this study, mevidalen (a selective positive allosteric modulator of the dopamine D1 receptor subtype) was shown to harness a novel mechanism of action that improves motor symptoms related to Lewy body dementia (LBD) on top of standard of care while improving or not worsening non-motor symptoms linked with conventional dopaminergic treatment.

• In this phase 2, 12-week study (PRESENCE), a total of 344 patients with LBD were randomized to (1:1:1:1) daily doses of mevidalen (10, 30, or 75 mg) or placebo in order to evaluate mevidalen’s safety and efficacy for treatment of cognition in patients with LBD.

• Alteration from baseline on Cognitive Drug Research Continuity of Attention composite score was the primary outcome measure.

• Primary or secondary cognition endpoints were not met by mevidalen, and mevidalen caused significant, dose-dependent improvements of MDS-UPDRS (Movement Disorder Society-Unified Parkinson's Disease Rating Scale) total score.

• Significant improvement in ADCS-CGIC (Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change) scores was achieved with 30 mg and 75 mg mevidalen doses vs placebo.

• In patients treated with 75 mg dose, the observed increases in blood pressure, adverse events, and cardiovascular serious adverse events were most pronounced.