- Alto Neuroscience's exploratory Phase 2 trial of ALTO-203 shows positive pharmacodynamic results in major depressive disorder patients.
- ALTO-203 improves attention and reduces EEG theta/beta ratio, an important biomarker for attentional control.
- The trial confirms the potential of ALTO-203 as a treatment for neuropsychiatric disorders with impaired attention and wakefulness.
Alto Neuroscience, Inc. (ANRO, Financial), a clinical-stage biopharmaceutical company, has announced promising results from its exploratory Phase 2 proof-of-concept trial of ALTO-203. The trial, involving 69 patients with major depressive disorder (MDD), identified a robust biomarker for patient selection and demonstrated positive pharmacodynamic activity. ALTO-203, a novel oral histamine H3 inverse agonist, aims to enhance cognition, wakefulness, and alertness in patients with elevated anhedonia levels.
The exploratory study confirmed that ALTO-203 significantly impacts objective measures of attention and wakefulness, with notable improvements linked to changes in the EEG theta/beta ratio—a key neurophysiological marker for attentional control. The findings replicated results from an earlier Phase 1 study in healthy volunteers, where the drug led to enhanced sustained attention and reductions in the EEG theta/beta ratio.
The trial was conducted in two sequential, double-blind, placebo-controlled periods, focusing on characterizing the pharmacodynamic, pharmacokinetic, safety, and tolerability profiles of ALTO-203 across two dosing levels. It was not, however, powered to detect statistical significance on traditional depression outcome scales.
Despite a higher-than-expected placebo response, ALTO-203 treatment showed significant improvements in sustained attention, particularly in patients with high baseline theta/beta ratios. Moreover, wearable device data supported the wake-promoting effects of ALTO-203, as both dosage levels exhibited significant increases in wakefulness compared to placebo.
The pharmacokinetic data revealed predictable drug accumulation with minimal adverse effects, reinforcing the safety profile of ALTO-203, although insomnia was the most frequent adverse event reported, consistent with its functionality as a wake-promoting agent. Further insights into the trial outcomes will be discussed at upcoming medical meetings as Alto Neuroscience determines the next steps for the development of ALTO-203.
