Alto Neurosciences Halts ALTO-101 PDE4 Inhibitor Development After Phase 2 Schizophrenia Trial Failure

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Alto Neurosciences discontinued development of ALTO-101, a transdermal PDE4 inhibitor, after it failed to meet the primary endpoint in a phase 2 trial for cognitive impairment associated with schizophrenia1

The phase 2 study evaluated 83 patients receiving 10 days of ALTO-101 treatment or placebo, with the primary endpoint being improvement in cognition measured by electroencephalography (EEG)1

ALTO-101 did not demonstrate statistically significant improvement on the primary EEG measure compared to placebo, though the company noted directional improvements on certain EEG biomarkers including a near-significant effect on theta-ITC in a subgroup of 59 more cognitively impaired patients1

The drug demonstrated a favorable tolerability profile with nausea and vomiting rates in line with placebo, suggesting better tolerability than other PDE4 inhibitors, though high rates of application site skin reactions were observed14

Alto will not pursue either the transdermal or modified-release oral formulation of ALTO-101 unless it finds a partner1

The company is shifting focus to ALTO-207, a combination therapy of pramipexole and ondansetron for treatment-resistant depression, which is expected to enter a phase 2b trial imminently1

Sources:

1. https://www.fiercebiotech.com/biotech/alto-halts-work-pde4-inhibitor-after-failed-phase-2-schizophrenia-study

4. https://www.biospace.com/press-releases/alto-neuroscience-reports-topline-data-from-phase-2-proof-of-concept-study-of-alto-101-and-highlights-pipeline-advancements