After completing a phase II proof-of-concept study, investigators reported on the efficacy and safety of BI 425809, a novel selective glycine transporter-1 (GlyT1) inhibitor, in the treatment of cognitive impairment associated with Alzheimer’s disease dementia.
Ultimately, the study’s authors found BI 425809 did not induce any clinically meaningful changes from baseline in neuropsychological assessments. The data were presented in Alzheimer’s Research & Therapy.
Novel GlyT1 Inhibitor Doesn’t Improve Dementia
The multicenter, double-blind study enrolled 610 patients (47% male; mean years of age, 72.9 ± 7.7) with mild-to-moderate probable Alzheimer’s disease dementia to undergo 12 weeks of treatment. Participants were evenly randomized to BI 425809 doses of 2 mg (n=123), 5 mg (n=122), 10 mg (n=122), or 25 mg (n=123), or to placebo (n=120).
The primary efficacy end point was the change from baseline in Alzheimer’s Disease Assessment Scale-Cognitive Subscale 11-item total score after week 12. Authors noted treatment compliance was above 97% for all groups.
According to the report, the median score for the Mini-Mental State Examination category was <22 in 287 (47%) patients and ≥22 in 322 patients. Crucially, the authors witnessed no clinically significant, non-flat dose-response relationship for the primary end point with BI 425809 (P>0.76 for all models).
Additionally, a total of 292 (47.9%) patients reported at least 1 adverse events during the treatment period. The authors did note the rate of investigator-defined drug-related adverse events was similar across all treatment groups, ranging from 15.4% to 19.5% in the BI 425809 arms and 15.8% for the placebo arm.
Notably, the article suggests the study was limited by its relatively short treatment duration and the broad range of disease severity among the enrolled patients. Furthermore, authors theorized some participants may have already progressed too far in Alzheimer’s disease dementia to benefit from GlyT1 inhibitor treatment.
Overall, the researchers concluded that BI 425809 was generally well tolerated, with no new safety signals observed in their study, but did not appear to induce any clinically meaningful benefit in cognitive impairment associated with Alzheimer’s disease dementia.
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