Transdermal PDE4 Inhibitor Fast Tracked for Cognitive Impairment in Schizophrenia

The Food and Drug Administration (FDA) has granted Fast Track designation to ALTO-101 for the treatment of cognitive impairment associated with schizophrenia (CIAS).

ALTO-101 is an investigational phosphodiesterase-4 (PDE4) inhibitor delivered via a transdermal patch. Inhibition of the PDE4 enzyme is expected to enhance neural circuits and improve cognitive function by increasing intracellular cyclic adenosine monophosphate (cAMP), which plays a key role in synaptic function.

The Fast Track designation is supported by data from a phase 1 trial in healthy adults demonstrating significantly greater drug exposure and fewer adverse events with ALTO-101 vs an oral PDE4 inhibitor. “Our phase 1 data, which demonstrated significant and clinically relevant effects of ALTO-101 on both EEG measures and cognitive performance in healthy subjects, provides strong validation for its mechanism,” said Amit Etkin, MD, PhD, founder and chief executive officer of Alto Neuroscience.

A phase 2 study (ClinicalTrials.gov Identifier: NCT06502964) is currently underway and is assessing ALTO-101 vs placebo on electroencephalogram (EEG) markers relevant to cognitive function in adult patients with CIAS. The primary endpoint of the study is the effect on theta band activity as measured using EEG at the end of each dose period. 

There are currently no FDA-approved treatments for CIAS, a disabling feature of the disease that includes impaired attention, memory, and executive function. “Receiving Fast Track designation from the FDA underscores the critical need for new, effective treatments for patients suffering from cognitive impairment associated with schizophrenia,” added Etkin.

This article originally appeared on MPR