GlyT1 Inhibitor Improves Cognition in Patients with Schizophrenia in Phase 2 Trial

Three months of daily, add-on treatment with the oral glycine transporter-1 (GlyT1) inhibitor BI 425809 improved cognition in patients with schizophrenia, according to results from a phase 2 study published in The Lancet Psychiatry.

“If these encouraging results are confirmed in phase 3 trials, BI 425809 could provide an effective treatment for cognitive impairment associated with schizophrenia,” researchers wrote.

Currently, no pharmacotherapy is available for the treatment of cognitive impairment associated with schizophrenia, researchers explained. The double-blind, phase 2 study, which was funded by Boehringer Ingelheim, included 509 outpatients between the ages of 18 and 50 who were on stable treatment for schizophrenia. The participants were from 81 centers in 11 countries.

Participants were randomized 1:1:1:1:2 to add-on, once-daily BI 425809 2 mg, BI 425809 5 mg, BI 425809 10 mg, BI 425809 25 mg, or placebo for 12 weeks.

Of 6 predefined dose-response models used to evaluate cognitive improvement, 5 found statistically significant benefit of BI 425809 compared with placebo, according to the study.

Changes from baseline in Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery overall composite T-score at week 12 were largest with the 10-mg and 25-mg doses of BI 425809 compared with placebo, researchers reported. Pairwise comparisons identified adjusted mean differences of 1.98 for the 10-mg dose and 1.73 for the 25-mg dose, suggesting no additional benefit of the 25-mg dose over the 10-mg dose.

Safety analyses showed rates of reported adverse event rates were similar across all participant groups: 59% in the BI 425809 2-mg group, 52% in the 5-mg group, 41% in the 10-mg group, 42% in the 25-mg group, and 44% in the placebo group.

“The findings of the present study support further investigation of the potential clinical benefits of BI 425809 in patients with schizophrenia. The cognitive benefits of BI 425809 might possibly be increased further by adjunctive cognitive stimulation, since GlyT1 inhibitors are hypothesized to promote activity-dependent neuroplasticity processes,” researchers wrote. “An ongoing study (NCT03859973) will explore the efficacy of BI 425809 10 mg in patients with schizophrenia on a background of computerized cognitive training.”

—Jolynn Tumolo

Reference

Fleischhacker WW, Podhorna J, Gröschl M, et al. Efficacy and safety of the novel glycine transporter inhibitor BI 425809 once daily in patients with schizophrenia: a double-blind, randomised, placebo-controlled phase 2 study. Lancet Psychiatry. 2021;8(3):191-201. doi: 10.1016/S2215-0366(20)30513-7