Results positive in study of PDE4 inhibitor for cognitive impairment in schizophrenia

A Bay Area biopharmaceutical firm has announced positive results from its phase 1 clinical trial in healthy volunteers of a novel PDE4 inhibitor being developed to treat those with cognitive impairment associated with schizophrenia.

According to a release from Alto Neuroscience Inc., results from the study, which examined safety, tolerability, pharmacokinetics and adhesion properties of the novel therapy, showed that ALTO-101 demonstrated favorable outcomes when administered via a transdermal patch compared with oral administration.

The study included a two-way crossover design consisting of two dosing periods. During the first period, 15 adults aged 40 to 64 years were given a single oral dose of 1 mg ALTO-101, following a 7-day washout. In the second period, all participants received continual transdermal dosing of 18 mg ALTO-101 for 2 days via patches worn for 24 hours.

According to results cited in the release, the patch delivered higher and more consistent concentrations of the drug compared with oral delivery. In addition, participants given ALTO-101 through transdermal delivery experienced a lower percentage of adverse events than those given the drug orally.

“Oral PDE4 inhibitors have shown great potential in a broad range of indications but have frequently been associated with dose-limiting side effect,” Amit Etkin, MD, PhD, founder and CEO of Alto Neuroscience, told Healio in an email. “These positive results demonstrate the importance of a transdermal delivery system to provide stable drug concentration and tolerability for patients and consistently reach dosage levels that impact cognitive brain circuitry.”

Alto further stated in the release it plans to initiate a proof-of-concept study evaluating ALTO-101 in patients with the condition during the first half of 2024, with topline data expected by the second half of 2025.